Music and the reduction of post-operative pain.

Science.gov (United States)

Dunn, Kelly

The prevention and treatment of post-operative pain, and the promotion of comfort are the challenges facing practitioners working in the recovery room setting. Surgical pain produces autonomic, psychological, immunological and behavioural responses that can delay or inhibit normal healing. Nurses spend more time with patients experiencing pain than any other healthcare professional. Therefore, they are in an ideal position to consider other pain-relieving strategies to complement the analgesics currently used. The studies reviewed cannot prove that music is effective in reducing post-operative pain, because the research methodology in the majority is poor. Patients, experience of listening to music post-operatively was positive, aiding distraction and increasing comfort. This shows the difference between inconsistent results for the objective measures of pain and what the patient is reporting.

Phenotypic changes in neutrophils related to anti-inflammatory therapy.

Science.gov (United States)

Barton, A E; Bayley, D L; Mikami, M; Llewellyn-Jones, C G; Stockley, R A

2000-01-03

Previous work from the group has shown that non-steroidal anti-inflammatory agents given to volunteers and patients inhibit PMN function possibly by affecting the developing neutrophil during the differentiation process. In this study indomethacin treatment in vivo reduced neutrophil chemotaxis and proteolytic degradation of fibronectin, with a maximal effect after 14 days. Stimulated neutrophil adherence to fibronectin was also reduced but this was not due to quantitative changes in beta(2) integrin expression or function. L-Selectin expression on resting and stimulated neutrophils was increased after 14 days and there was a small decrease in plasma levels of soluble L-selectin. These effects, however, could not be reproduced by treatment of neutrophils with indomethacin in vitro, suggesting they are due to effects on differentiating/maturing PMNs. In an attempt to interpret these changes, studies were performed with dexamethasone, which is known to alter neutrophil function and kinetics. Dexamethasone treatment reduced chemotaxis and increased superoxide generation after 1 day and was associated with increased expression of activated beta(2) integrins and reduced L-selectin expression on resting neutrophils. This suggests the appearance of mainly 'activated' cells as a result of demargination and indicates that the effects of indomethacin are distinctive and not related to changes in compartmentalisation.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

Science.gov (United States)

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Spontaneous neutrophil migration patterns during sepsis after major burns.

Science.gov (United States)

Jones, Caroline N; Moore, Molly; Dimisko, Laurie; Alexander, Andrew; Ibrahim, Amir; Hassell, Bryan A; Warren, H Shaw; Tompkins, Ronald G; Fagan, Shawn P; Irimia, Daniel

2014-01-01

Finely tuned to respond quickly to infections, neutrophils have amazing abilities to migrate fast and efficiently towards sites of infection and inflammation. Although neutrophils ability to migrate is perturbed in patients after major burns, no correlations have yet been demonstrated between altered migration and higher rate of infections and sepsis in these patients when compared to healthy individuals. To probe if such correlations exist, we designed microfluidic devices to quantify the neutrophil migration phenotype with high precision. Inside these devices, moving neutrophils are confined in channels smaller than the neutrophils and forced to make directional decisions at bifurcations and around posts. We employed these devices to quantify neutrophil migration across 18 independent parameters in 74 blood samples from 13 patients with major burns and 3 healthy subjects. Blinded, retrospective analysis of clinical data and neutrophil migration parameters revealed that neutrophils isolated from blood samples collected during sepsis migrate spontaneously inside the microfluidic channels. The spontaneous neutrophil migration is a unique phenotype, typical for patients with major burns during sepsis and often observed one or two days before the diagnosis of sepsis is confirmed. The spontaneous neutrophil migration phenotype is rare in patients with major burns in the absence of sepsis, and is not encountered in healthy individuals. Our findings warrant further studies of neutrophils and their utility for early diagnosing and monitoring sepsis in patients after major burns.

Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

Science.gov (United States)

Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

2014-03-01

Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo.

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Colom, Bartomeu; Bodkin, Jennifer V; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A; Nourshargh, Sussan

2015-06-16

Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

NFκB1 is a suppressor of neutrophil-driven hepatocellular carcinoma

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Wilson, C. L.; Jurk, D.; Fullard, N.; Banks, P.; Page, A.; Luli, S.; Elsharkawy, A. M.; Gieling, R. G.; Chakraborty, J. Bagchi; Fox, C.; Richardson, C.; Callaghan, K.; Blair, G. E.; Fox, N.; Lagnado, A.; Passos, J. F.; Moore, A. J.; Smith, G. R.; Tiniakos, D. G.; Mann, J.; Oakley, F.; Mann, D. A.

2015-04-01

Hepatocellular carcinoma (HCC) develops on the background of chronic hepatitis. Leukocytes found within the HCC microenvironment are implicated as regulators of tumour growth. We show that diethylnitrosamine (DEN)-induced murine HCC is attenuated by antibody-mediated depletion of hepatic neutrophils, the latter stimulating hepatocellular ROS and telomere DNA damage. We additionally report a previously unappreciated tumour suppressor function for hepatocellular nfkb1 operating via p50:p50 dimers and the co-repressor HDAC1. These anti-inflammatory proteins combine to transcriptionally repress hepatic expression of a S100A8/9, CXCL1 and CXCL2 neutrophil chemokine network. Loss of nfkb1 promotes ageing-associated chronic liver disease (CLD), characterized by steatosis, neutrophillia, fibrosis, hepatocyte telomere damage and HCC. Nfkb1S340A/S340Amice carrying a mutation designed to selectively disrupt p50:p50:HDAC1 complexes are more susceptible to HCC; by contrast, mice lacking S100A9 express reduced neutrophil chemokines and are protected from HCC. Inhibiting neutrophil accumulation in CLD or targeting their tumour-promoting activities may offer therapeutic opportunities in HCC.

Use of steroids in rhinoplasty with lateral osteotomies for reducing post operative oedema

International Nuclear Information System (INIS)

Sanober, A.; Rashid, M.; Khan, M.I.; Rehman, S.U.; Fatima, S.; Hussain, A.

2018-01-01

Postoperative periorbital edema is a commonly encountered side effect of rhinoplasties in which lateral osteotomies have been incorporated. It dissatisfies the surgeon as well as the patient. Osteotomies are done at the end of all soft tissue manipulation to reduce the development of edema. The aim of this study was to determine the efficacy of intravenous dexamethasone in reducing edema in patients who undergo rhinoplasty with lateral osteotomies. Methods A Prospective randomized controlled trial was done at department of plastic and reconstructive surgery, Shifa International Hospital Islamabad. Sixty patients age between 16- 55 requiring open rhinoplasty were taken for this study and divided in two groups. One group received dexamethasone 8mg intravenously peroperatively and second dose 4 hours postoperatively. The second group did not receive anything. Both groups were assessed on first post operative day and 7th day for periorbital edema. Result The overall decrease in edema in patients who received steroid was by 50% while in control group was 33.3%. By the 7th day control group 13.3% patients had grade III edema as compared to 3.33% in steroid group. Chi test was applied and p value of 0.0289 was obtained which was found to be statistically very significant. Conclusion Dexamethasone used in minimal dosage showed significant advantage in reducing periorbital edema after rhinoplasty with no evidence of any side effects secondary to steroid administration. (author)

Alcohol Consumption Increases Post-Operative Infection but Not Mortality

DEFF Research Database (Denmark)

Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue

2015-01-01

BACKGROUND: Alcohol consumption causes multiple comorbidities with potentially negative outcome after operations. The aims are to study the association between alcohol consumption and post-operative non-surgical site infections and mortality and to determine the impact of peri-operative...... alcohol consumption and mortality was found. Meta-analyses of RCTs showed that interventions reduce infections but not mortality in patients with alcohol abuse. CONCLUSIONS: Consumption of more than two units of alcohol per day increases post-operative non-surgical site infections. Alcohol...... for observational studies and RCTs. RESULTS: Thirteen observational studies and five RCTs were identified. Meta-analyses of observational studies showed more infections in those consuming more than two units of alcohol per day compared with drinking less in both unadjusted and adjusted data. No association between...

A randomised control trial on the use of topical methicillin in reducing post-operative ventriculoperitoneal shunt infection.

Science.gov (United States)

Theophilus, Sharon Casilda; Adnan, Johari Siregar

2011-01-01

A double-blind randomised control study was conducted on all patients who were admitted or referred to the Department of Neurosurgery, Sultanah Aminah Hospital, Johor Bahru, with a diagnosis of hydrocephalus where a ventriculoperitoneal shunt was indicated. The period of study was from November 2005 to May 2007, and the follow-up period was 3 months after surgery. Randomisation was carried out in the operating room prior to the procedure. The scrub nurse selected a sealed envelope, which contained the assignment of each patient to 1 of 2 treatment groups: Group 1 patients were treated with topical methicillin, and Group 2 patients were not treated with topical methicillin. Prophylactic antibiotic, cefuroxime (25 mg/kg) was given intravenously at induction. Standard sterile operative technique was followed in preparing and draping the patients. A total of 90 patients were recruited in the study, and 13 (14.4%) patients developed an infection within 3 months post-operation. Group 1 had a 8.9% risk of infection, and Group 2 had a 20% risk; however, there was no statistically significant post-operative ventriculoperitoneal shunt (VPS) infection reduction with the use of topical methicillin in VPS surgery (P = 0.230). Multivariate analysis showed that only duration of surgery had a significant influence on the incidence of post-operative VPS infection in the non-methicillin group (P = 0.02). The non-methicillin group had an 8 times greater risk of developing post-operative VPS infection than the methicillin group if surgery lasted longer than 1 hour. Topical methicillin had no significance in the reduction of post-operative VPS infection.

Autophagy Primes Neutrophils for Neutrophil Extracellular Trap Formation during Sepsis.

Science.gov (United States)

Park, So Young; Shrestha, Sanjeeb; Youn, Young-Jin; Kim, Jun-Kyu; Kim, Shin-Yeong; Kim, Hyun Jung; Park, So-Hee; Ahn, Won-Gyun; Kim, Shin; Lee, Myung Goo; Jung, Ki-Suck; Park, Yong Bum; Mo, Eun-Kyung; Ko, Yousang; Lee, Suh-Young; Koh, Younsuck; Park, Myung Jae; Song, Dong-Keun; Hong, Chang-Won

2017-09-01

Neutrophils are key effectors in the host's immune response to sepsis. Excessive stimulation or dysregulated neutrophil functions are believed to be responsible for sepsis pathogenesis. However, the mechanisms regulating functional plasticity of neutrophils during sepsis have not been fully determined. We investigated the role of autophagy in neutrophil functions during sepsis in patients with community-acquired pneumonia. Neutrophils were isolated from patients with sepsis and stimulated with phorbol 12-myristate 13-acetate (PMA). The levels of reactive oxygen species generation, neutrophil extracellular trap (NET) formation, and granule release, and the autophagic status were evaluated. The effect of neutrophil autophagy augmentation was further evaluated in a mouse model of sepsis. Neutrophils isolated from patients who survived sepsis showed an increase in autophagy induction, and were primed for NET formation in response to subsequent PMA stimulation. In contrast, neutrophils isolated from patients who did not survive sepsis showed dysregulated autophagy and a decreased response to PMA stimulation. The induction of autophagy primed healthy neutrophils for NET formation and vice versa. In a mouse model of sepsis, the augmentation of autophagy improved survival via a NET-dependent mechanism. These results indicate that neutrophil autophagy primes neutrophils for increased NET formation, which is important for proper neutrophil effector functions during sepsis. Our study provides important insights into the role of autophagy in neutrophils during sepsis.

Leukotriene B4-Neutrophil Elastase Axis Drives Neutrophil Reverse Transendothelial Cell Migration In Vivo

Science.gov (United States)

Colom, Bartomeu; Bodkin, Jennifer V.; Beyrau, Martina; Woodfin, Abigail; Ody, Christiane; Rourke, Claire; Chavakis, Triantafyllos; Brohi, Karim; Imhof, Beat A.; Nourshargh, Sussan

2015-01-01

Summary Breaching endothelial cells (ECs) is a decisive step in the migration of leukocytes from the vascular lumen to the extravascular tissue, but fundamental aspects of this response remain largely unknown. We have previously shown that neutrophils can exhibit abluminal-to-luminal migration through EC junctions within mouse cremasteric venules and that this response is elicited following reduced expression and/or functionality of the EC junctional adhesion molecule-C (JAM-C). Here we demonstrate that the lipid chemoattractant leukotriene B4 (LTB4) was efficacious at causing loss of venular JAM-C and promoting neutrophil reverse transendothelial cell migration (rTEM) in vivo. Local proteolytic cleavage of EC JAM-C by neutrophil elastase (NE) drove this cascade of events as supported by presentation of NE to JAM-C via the neutrophil adhesion molecule Mac-1. The results identify local LTB4-NE axis as a promoter of neutrophil rTEM and provide evidence that this pathway can propagate a local sterile inflammatory response to become systemic. PMID:26047922

A Randomised Control Trial on the Use of Topical Methicillin in Reducing Post-Operative Ventriculoperitoneal Shunt Infection

Science.gov (United States)

Theophilus, Sharon Casilda; Adnan, Johari Siregar

2011-01-01

Background: A double-blind randomised control study was conducted on all patients who were admitted or referred to the Department of Neurosurgery, Sultanah Aminah Hospital, Johor Bahru, with a diagnosis of hydrocephalus where a ventriculoperitoneal shunt was indicated. Methods: The period of study was from November 2005 to May 2007, and the follow-up period was 3 months after surgery. Randomisation was carried out in the operating room prior to the procedure. The scrub nurse selected a sealed envelope, which contained the assignment of each patient to 1 of 2 treatment groups: Group 1 patients were treated with topical methicillin, and Group 2 patients were not treated with topical methicillin. Prophylactic antibiotic, cefuroxime (25 mg/kg) was given intravenously at induction. Standard sterile operative technique was followed in preparing and draping the patients. Results: A total of 90 patients were recruited in the study, and 13 (14.4%) patients developed an infection within 3 months post-operation. Group 1 had a 8.9% risk of infection, and Group 2 had a 20% risk; however, there was no statistically significant post-operative ventriculoperitoneal shunt (VPS) infection reduction with the use of topical methicillin in VPS surgery (P = 0.230). Multivariate analysis showed that only duration of surgery had a significant influence on the incidence of post-operative VPS infection in the non-methicillin group (P = 0.02). The non-methicillin group had an 8 times greater risk of developing post-operative VPS infection than the methicillin group if surgery lasted longer than 1 hour. Conclusion: Topical methicillin had no significance in the reduction of post-operative VPS infection. PMID:22135571

Adenosine triphosphate hydrolysis reduces neutrophil infiltration and necrosis in partial-thickness scald burns in mice.

Science.gov (United States)

Bayliss, Jill; Delarosa, Sara; Wu, Jianfeng; Peterson, Jonathan R; Eboda, Oluwatobi N; Su, Grace L; Hemmila, Mark; Krebsbach, Paul H; Cederna, Paul S; Wang, Stewart C; Xi, Chuanwu; Levi, Benjamin

2014-01-01

Extracellular adenosine triphosphate (ATP), present in thermally injured tissue, modulates the inflammatory response and causes significant tissue damage. The authors hypothesize that neutrophil infiltration and ensuing tissue necrosis would be mitigated by removing ATP-dependent signaling at the burn site. Mice were subjected to 30% TBSA partial-thickness scald burn by dorsal skin immersion in a water bath at 60 or 20°C (nonburn controls). In the treatment arm, an ATP hydrolyzing enzyme, apyrase, was applied directly to the site immediately after injury. Skin was harvested after 24 hours and 5 days for hematoxylin and eosin stain, elastase, and Ki-67 staining. Tumor necrosis factor (TNF)-α and interferon (IFN)-β expression were measured through quantitative real-time polymerase chain reaction. At 24 hours, the amount of neutrophil infiltration was different between the burn and burn + apyrase groups (P burn group at 24 hours and 5 days. TNF-α and IFN-β expression at 24 hours in the apyrase group was lower than in the burn group (P burn site allays the neutrophil response to thermal injury and reduces tissue necrosis. This decrease in inflammation and tissue necrosis is at least partially because of TNF-α and IFN-β signaling. Apyrase could be used as topical inflammatory regulators to quell the injury caused by inflammation.

Anaplasma phagocytophilum inhibits human neutrophil apoptosis via upregulation of bfl-1, maintenance of mitochondrial membrane potential and prevention of caspase 3 activation.

Science.gov (United States)

Ge, Yan; Yoshiie, Kiyotaka; Kuribayashi, Futoshi; Lin, Mingqun; Rikihisa, Yasuko

2005-01-01

The inhibition of neutrophil apoptosis plays a central role in human granulocytic anaplasmosis. Intracellular signalling pathways through which the obligatory intracellular bacterium Anaplasma phagocytophilum inhibits the spontaneous apoptosis of human peripheral blood neutrophils were investigated. bfl-1 mRNA levels in uninfected neutrophils after 12 h in culture were reduced to approximately 5-25% of 0 h levels, but remained high in infected neutrophils. The eukaryotic RNA synthesis inhibitor, actinomycin D, prevented the maintenance of bfl-1 mRNA levels by A. phagocytophilum. Differences in mcl-1, bax, bcl-w, bad or bak mRNA levels in infected versus uninfected neutrophils were not remarkable. By using mitochondrial fluorescent dyes, Mitotracker Red and JC-1, it was found that most uninfected neutrophils lost mitochondrial membrane potential after 10-12 h incubation, whereas A. phagocytophilum-infected neutrophils maintained high membrane potential. Caspase 3 activity and the degree of apoptosis were lower in dose-dependent manner in A. phagocytophilum-infected neutrophils at 16 h post infection, as compared to uninfected neutrophils. Anti-active caspase 3 antibody labelling showed less positively stained population in infected neutrophils compared to those in uninfected neutrophils after 12 h incubation. These results suggest that A. phagocytophilum inhibits human neutrophil apoptosis via transcriptional upregulation of bfl-1 and inhibition of mitochondria-mediated activation of caspase 3.

The "Propeller" incision for transpalatal advancement pharyngoplasty: a new approach to reduce post-operative oronasal fistulae.

Science.gov (United States)

Shine, Neville Patrick; Lewis, Richard Hamilton

2008-09-01

To present a new soft tissue approach for transpalatal advancement pharyngoplasty (TPA), the propeller incision, and to compare the rates of post-operative oronasal fistula in those undergoing TPA with the traditional "Gothic Arch" incision described by Woodson and those with the propeller incision. A prospectively maintained adult sleep apnoea surgery database was used to identify those patients undergoing TPA, either alone or in combination with other procedures, for obstructive sleep apnoea syndrome (OSAS) between February 2001 and September 2006 in a tertiary referral centre by a single surgeon (RHL). In addition to the incision used during TPA, patient demographic data, previous surgery of the upper airways, smoking history, pre-operative body mass index, respiratory disturbance index, oxygen saturation index and the occurrence of oronasal fistula post-operatively, were recorded. The propeller incision technique is described. A total of 89 patients who underwent TPA were identified. A total of 49 patients had a "Gothic Arch" incision and 40 had a "Propeller" incision. The two groups of patients were comparable in age, sex, previous tonsillar and uvulopalatopharyngoplasty surgery, smoking histories and pre-operative disease severity. In the "Gothic Arch" group, eight patients (16%) developed oronasal fistulae in the post-operative period versus only one patient (2.5%) in the "Propeller" group. The difference between the two groups was statistically significant (P=0.038, Fisher's exact test). Of the total cases with post-operative oronasal fistula (n=9), only one patient (from the Gothic Arch incision group) required operative closure which was performed under local anesthesia and healed without complication. The propeller incision provides an anatomically sensible axial-based flap that provides adequate access to perform TPA. It is associated with a lower incidence of oronasal fistula and is recommended by the authors.

Pre-operative assessment and post-operative care in elective shoulder surgery.

Science.gov (United States)

Akhtar, Ahsan; Macfarlane, Robert J; Waseem, Mohammad

2013-01-01

Pre-operative assessment is required prior to the majority of elective surgical procedures, primarily to ensure that the patient is fit to undergo surgery, whilst identifying issues that may need to be dealt with by the surgical or anaesthetic teams. The post-operative management of elective surgical patients begins during the peri-operative period and involves several health professionals. Appropriate monitoring and repeated clinical assessments are required in order for the signs of surgical complications to be recognised swiftly and adequately. This article examines the literature regarding pre-operative assessment in elective orthopaedic surgery and shoulder surgery, whilst also reviewing the essentials of peri- and post-operative care. The need to recognise common post-operative complications early and promptly is also evaluated, along with discussing thromboprophylaxis and post-operative analgesia following shoulder surgery.

Clinical target volume delineation in glioblastomas: pre-operative versus post-operative/pre-radiotherapy MRI

Science.gov (United States)

Farace, P; Giri, M G; Meliadò, G; Amelio, D; Widesott, L; Ricciardi, G K; Dall'Oglio, S; Rizzotti, A; Sbarbati, A; Beltramello, A; Maluta, S; Amichetti, M

2011-01-01

Objectives Delineation of clinical target volume (CTV) is still controversial in glioblastomas. In order to assess the differences in volume and shape of the radiotherapy target, the use of pre-operative vs post-operative/pre-radiotherapy T1 and T2 weighted MRI was compared. Methods 4 CTVs were delineated in 24 patients pre-operatively and post-operatively using T1 contrast-enhanced (T1PRECTV and T1POSTCTV) and T2 weighted images (T2PRECTV and T2POSTCTV). Pre-operative MRI examinations were performed the day before surgery, whereas post-operative examinations were acquired 1 month after surgery and before chemoradiation. A concordance index (CI) was defined as the ratio between the overlapping and composite volumes. Results The volumes of T1PRECTV and T1POSTCTV were not statistically different (248 ± 88 vs 254 ± 101), although volume differences >100 cm3 were observed in 6 out of 24 patients. A marked increase due to tumour progression was shown in three patients. Three patients showed a decrease because of a reduced mass effect. A significant reduction occurred between pre-operative and post-operative T2 volumes (139 ± 68 vs 78 ± 59). Lack of concordance was observed between T1PRECTV and T1POSTCTV (CI = 0.67 ± 0.09), T2PRECTV and T2POSTCTV (CI = 0.39 ± 0.20) and comparing the portion of the T1PRECTV and T1POSTCTV not covered by that defined on T2PRECTV images (CI = 0.45 ± 0.16 and 0.44 ± 0.17, respectively). Conclusion Using T2 MRI, huge variations can be observed in peritumoural oedema, which are probably due to steroid treatment. Using T1 MRI, brain shifts after surgery and possible progressive enhancing lesions produce substantial differences in CTVs. Our data support the use of post-operative/pre-radiotherapy T1 weighted MRI for planning purposes. PMID:21045069

Does Post Septoplasty Nasal Packing Reduce Complications?

Directory of Open Access Journals (Sweden)

Bijan Naghibzadeh

2011-01-01

Full Text Available The main issues in nasal surgery are to stabilize the nose in the good position after surgery and preserve the cartilages and bones in the favorable situation and reduce the risk of deviation recurrence. Also it is necessary to avoid the synechia formation, nasal valve narrowing, hematoma and bleeding. Due to the above mentioned problems and in order to solve and minimize them nasal packing, nasal splint and nasal mold have been advised. Patients for whom the nasal packing used may faced to some problems like naso-pulmonary reflex, intractable pain, sleep disorder, post operation infection and very dangerous complication like toxic shock syndrome. We have two groups of patients and three surgeons (one of the surgeons used post operative nasal packing in his patients and the two others surgeons did not.Complications and morbidities were compared in these two groups. Comparing the two groups showed that the rate of complication and morbidities between these two groups were same and the differences were not valuable, except the pain and discomfort post operatively and at the time of its removal. Nasal packing has several risks for the patients while its effects are not studied. Septoplasty can be safely performed without postoperative nasal packing. Nasal packing had no main findings that compensated its usage. Septal suture is one of the procedures that can be used as alternative method to nasal packing. Therefore the nasal packing after septoplasty should be reserved for the patients with increased risk of bleeding.

Neutrophil labeling with [99mTc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

International Nuclear Information System (INIS)

Gallagher, Hayley; Ramsay, Stuart C.; Barnes, Jodie; Maggs, Jacqueline; Cassidy, Nathan; Ketheesan, Natkunam

2006-01-01

Introduction: [ 99m Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection

Genetic Deletion and Pharmacological Inhibition of PI3Kγ Reduces Neutrophilic Airway Inflammation and Lung Damage in Mice with Cystic Fibrosis-Like Lung Disease

Directory of Open Access Journals (Sweden)

Maria Galluzzo

2015-01-01

Full Text Available Purpose. Neutrophil-dominated airway inflammation is a key feature of progressive lung damage in cystic fibrosis (CF. Thus, reducing airway inflammation is a major goal to prevent lung damage in CF. However, current anti-inflammatory drugs have shown several limits. PI3Kγ plays a pivotal role in leukocyte recruitment and activation; in the present study we determined the effects of genetic deletion and pharmacologic inhibition of PI3Kγ on airway inflammation and structural lung damage in a mouse model of CF lung disease. Methods. βENaC overexpressing mice (βENaC-Tg were backcrossed with PI3Kγ-deficient (PI3KγKO mice. Tissue damage was assessed by histology and morphometry and inflammatory cell number was evaluated in bronchoalveolar lavage fluid (BALF. Furthermore, we assessed the effect of a specific PI3Kγ inhibitor (AS-605240 on inflammatory cell number in BALF. Results. Genetic deletion of PI3Kγ decreased neutrophil numbers in BALF of PI3KγKO/βENaC-Tg mice, and this was associated with reduced emphysematous changes. Treatment with the PI3Kγ inhibitor AS-605240 decreased the number of neutrophils in BALF of βENaC-Tg mice, reproducing the effect observed with genetic deletion of the enzyme. Conclusions. These results demonstrate the biological efficacy of both genetic deletion and pharmacological inhibition of PI3Kγ in reducing chronic neutrophilic inflammation in CF-like lung disease in vivo.

Modulation and Apoptosis of Neutrophil Granulocytes by Extracorporeal Photopheresis in the Treatment of Chronic Graft-Versus-Host Disease.

Directory of Open Access Journals (Sweden)

Cindy Franklin

Full Text Available Chronic graft-versus-host disease (cGVHD is a common side effect of allogeneic stem cell transplantation and a major cause of morbidity and mortality in affected patients. Especially skin, eyes and oral mucosa are affected. This can lead to pain and functional impairment. Extracorporeal photopheresis (ECP is an effective immunomodulatory therapy with minimal side effects but its mode of action is still largely unknown. The objective of the present study was to examine the effects of ECP on neutrophil granulocytes in patients with cGVHD. Analysis of leukocytes from cGVHD patients obtained from the ECP device during treatment showed that neutrophil granulocytes account for the majority of cells treated during ECP. Neutrophils from healthy donors treated in vitro with 8-methoxypsoralen and UVA light as well as neutrophils from buffy coats of patients with cGVHD treated by ECP showed increased apoptosis and decreased half-life. In remaining non-apoptotic cells chemoirradiation resulted in loss of activation markers and reduced effector functions. This was accompanied by an increase in extracellular arginase-1 activity. Additional comparison of neutrophils isolated from blood of cGVHD patients before and 24h after ECP revealed a decreased half-life and reduction of effector functions of post-ECP neutrophils ex vivo. These observations strongly suggest that ECP induces both apoptosis and physiological changes in neutrophils and that these changes also take place in vivo. This study is the first to show that ECP modulates apoptosis and inflammatory activity in neutrophil granulocytes, indicating that neutrophils may significantly contribute to the overall immunomodulatory effects attributed to this treatment.

Neutrophil labeling with [{sup 99m}Tc]-technetium stannous colloid is complement receptor 3-mediated and increases the neutrophil priming response to lipopolysaccharide

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Gallagher, Hayley [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Ramsay, Stuart C. [School of Medicine, James Cook University, Townsville, Queensland (Australia) and Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia)]. E-mail: stuart.ramsey@jcu.edu.au; Barnes, Jodie [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); Maggs, Jacqueline [Department of Nuclear Medicine, Townsville Hospital, Townsville, Queensland 4814 (Australia); Cassidy, Nathan [Townsville Nuclear Medicine, Mater Hospital, Townsville, Queensland 4812 (Australia); Ketheesan, Natkunam [School of Veterinary and Biomedical Sciences, James Cook University, Townsville, Queensland 4811 (Australia); School of Medicine, James Cook University, Townsville, Queensland (Australia)

2006-04-15

Introduction: [{sup 99m}Tc]-technetium stannous colloid (TcSnC)-labeled white cells are used to image inflammation. Neutrophil labeling with TcSnC is probably phagocytic, but the phagocytic receptor involved is not known. We hypothesised that complement receptor 3 (CR3) plays a key role. Phagocytic labeling could theoretically result in neutrophil activation or priming, affecting the behaviour of labeled cells. Fluorescence-activated cell sorter (FACS) analysis side scatter measurements can assess neutrophil activation and priming. Methods: We tested whether TcSnC neutrophil labeling is CR3-mediated by assessing if neutrophil uptake of TcSnC was inhibited by a monoclonal antibody (mAb) directed at the CD11b component of CR3. We tested if TcSnC-labeled neutrophils show altered activation or priming status, comparing FACS side scatter in labeled and unlabeled neutrophils and examining the effect of lipopolysaccharide (LPS), a known priming agent. Results: Anti-CD11b mAb reduced neutrophil uptake of TcSnC in a dose-dependent fashion. Labeled neutrophils did not show significantly increased side scatter compared to controls. LPS significantly increased side scatter in control cells and labeled neutrophils. However, the increase was significantly greater in labeled neutrophils than unlabeled cells. Conclusions: Neutrophil labeling with TcSnC is related to the function of CR3, a receptor which plays a central role in phagocytosis. TcSnC labeling did not significantly activate or prime neutrophils. However, labeled neutrophils showed a greater priming response to LPS. This could result in labeled neutrophils demonstrating increased adhesion on activated endothelium at sites of infection.

Interval and continuous exercise regimens suppress neutrophil-derived microparticle formation and neutrophil-promoted thrombin generation under hypoxic stress.

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Chen, Yi-Ching; Ho, Ching-Wen; Tsai, Hsing-Hua; Wang, Jong-Shyan

2015-04-01

Acute hypoxic exposure increases vascular thrombotic risk. The release of procoagulant-rich microparticles from neutrophils accelerates the pathogenesis of inflammatory thrombosis. The present study explicates the manner in which interval and continuous exercise regimens affect neutrophil-derived microparticle (NDMP) formation and neutrophil/NDMP-mediated thrombin generation (TG) under hypoxic condition. A total of 60 sedentary males were randomized to perform either aerobic interval training [AIT; 3-min intervals at 40% and 80% V̇O2max (maximal O2 consumption)] or moderate continuous training (MCT; sustained 60% V̇O2max) for 30 min/day, 5 days/week for 5 weeks, or to a control (CTL) group who did not receive any form of training. At rest and immediately after hypoxic exercise test (HE, 100 W under 12% O2 for 30 min), the NDMP characteristics and dynamic TG were measured by flow cytometry and thrombinography respectively. Before the intervention, HE (i) elevated coagulant factor VIII/fibrinogen concentrations and shortened activated partial thromboplastin time (aPTT), (ii) increased total and tissue factor (TF)-rich/phosphatidylserine (PS)-exposed NDMP counts and (iii) enhanced the peak height and rate of TG promoted by neutrophils/NDMPs. Following the 5-week intervention, AIT exhibited higher enhancement of V̇O2max than did MCT. Notably, both MCT and AIT attenuated the extents of HE-induced coagulant factor VIII/fibrinogen elevations and aPTT shortening. Furthermore, the two exercise regimens significantly decreased TF-rich/PS-exposed NDMP formation and depressed neutrophil/NDMP-mediated dynamic TG at rest and following HE. Hence, we conclude that AIT is superior to MCT for enhancing aerobic capacity. Moreover, either AIT or MCT effectively ameliorates neutrophil/NDMP-promoted TG by down-regulating expression of procoagulant factors during HE, which may reduce thrombotic risk evoked by hypoxia. Moreover, either AIT or MCT effectively ameliorates neutrophil

Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

LENUS (Irish Health Repository)

Hong, Ying

2012-01-01

The mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.

Chronic neutrophilic leukemia.

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Bredeweg, Arthur; Burch, Micah; Krause, John R

2018-01-01

Chronic neutrophilic leukemia is a rare myeloproliferative disorder characterized by a sustained peripheral blood neutrophilia, absence of the BCR/ABL oncoprotein, bone marrow hypercellularity with less than 5% myeloblasts and normal neutrophil maturation, and no dysplasia. This leukemia has been associated with mutations in the colony-stimulating factor 3 receptor (CSF3R) that may activate this receptor, leading to the proliferation of neutrophils that are the hallmark of chronic neutrophilic leukemia. We present a case of chronic neutrophilic leukemia and discuss the criteria for diagnosis and the significance of mutations found in this leukemia.

Air quality monitoring of the post-operative recovery room and locations surrounding operating theaters in a medical center in Taiwan.

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Chin-Sheng Tang

Full Text Available To prevent surgical site infection (SSI, the airborne microbial concentration in operating theaters must be reduced. The air quality in operating theaters and nearby areas is also important to healthcare workers. Therefore, this study assessed air quality in the post-operative recovery room, locations surrounding the operating theater area, and operating theaters in a medical center. Temperature, relative humidity (RH, and carbon dioxide (CO2, suspended particulate matter (PM, and bacterial concentrations were monitored weekly over one year. Measurement results reveal clear differences in air quality in different operating theater areas. The post-operative recovery room had significantly higher CO2 and bacterial concentrations than other locations. Bacillus spp., Micrococcus spp., and Staphylococcus spp. bacteria often existed in the operating theater area. Furthermore, Acinetobacter spp. was the main pathogen in the post-operative recovery room (18% and traumatic surgery room (8%. The mixed effect models reveal a strong correlation between number of people in a space and high CO2 concentration after adjusting for sampling locations. In conclusion, air quality in the post-operative recovery room and operating theaters warrants attention, and merits long-term surveillance to protect both surgical patients and healthcare workers.

Air quality monitoring of the post-operative recovery room and locations surrounding operating theaters in a medical center in Taiwan.

Science.gov (United States)

Tang, Chin-Sheng; Wan, Gwo-Hwa

2013-01-01

To prevent surgical site infection (SSI), the airborne microbial concentration in operating theaters must be reduced. The air quality in operating theaters and nearby areas is also important to healthcare workers. Therefore, this study assessed air quality in the post-operative recovery room, locations surrounding the operating theater area, and operating theaters in a medical center. Temperature, relative humidity (RH), and carbon dioxide (CO2), suspended particulate matter (PM), and bacterial concentrations were monitored weekly over one year. Measurement results reveal clear differences in air quality in different operating theater areas. The post-operative recovery room had significantly higher CO2 and bacterial concentrations than other locations. Bacillus spp., Micrococcus spp., and Staphylococcus spp. bacteria often existed in the operating theater area. Furthermore, Acinetobacter spp. was the main pathogen in the post-operative recovery room (18%) and traumatic surgery room (8%). The mixed effect models reveal a strong correlation between number of people in a space and high CO2 concentration after adjusting for sampling locations. In conclusion, air quality in the post-operative recovery room and operating theaters warrants attention, and merits long-term surveillance to protect both surgical patients and healthcare workers.

Late post-operative hypoxaemia and organ dysfunction

DEFF Research Database (Denmark)

Kehlet, H; Rosenberg, J

1995-01-01

an adverse effect of tissue hypoxia on wound healing and on resistance to bacterial wound infections. Finally, mental confusion and surgical delirium may be related to inadequate arterial oxygenation during the late post-operative period. Late post-operative constant and episodic hypoxaemia may therefore......Constant and episodic hypoxaemia are common after major operations in the late post-operative period in the surgical ward. Recent studies have shown that hypoxaemia may be related to the development of myocardial ischaemia and cardiac arrhythmias. Experimental and clinical studies have demonstrated...

Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

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Scharrig, Emilia; Carestia, Agostina; Ferrer, María F.; Cédola, Maia; Pretre, Gabriela; Drut, Ricardo; Picardeau, Mathieu; Schattner, Mirta; Gómez, Ricardo M.

2015-01-01

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden. PMID:26161745

Neutrophils at work

DEFF Research Database (Denmark)

Nauseef, William M; Borregaard, Niels

2014-01-01

In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from ...

Neutrophils in critical illness.

Science.gov (United States)

McDonald, Braedon

2018-03-01

During critical illness, dramatic alterations in neutrophil biology are observed including abnormalities of granulopoeisis and lifespan, cell trafficking and antimicrobial effector functions. As a result, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. In this article, the role of neutrophils in the pathogenesis of critical illness (sepsis, trauma, burns and others) will be explored, including pathological changes to neutrophil function during critical illness and the utility of monitoring aspects of the neutrophil phenotype as biomarkers for diagnosis and prognostication. Lastly, we review findings from clinical trials of therapies that target the harmful effects of neutrophils, providing a bench-to-bedside perspective on neutrophils in critical illness.

is there an increased risk of post-operative surgical site infection

African Journals Online (AJOL)

2012-09-06

Sep 6, 2012 ... requiring implant orthopaedic surgery are at an increased risk for post-operative surgical ... further studies should determine the effect of reduced CD4 counts, viral load .... Language not Enlish, French, Ducth or German (n=2).

Minimally traumatic stapes surgery for otosclerosis: Risk reduction of post-operative vertigo

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An-Suey Shiao

2018-06-01

Full Text Available Background: The author (Dr. Shiao modified traditional stapes surgery (TSS specifically for patients with otosclerosis. The proposed technique, referred to as minimally traumatic stapes surgery (MTSS, reduces the risk of subjective discomfort (i.e. vertigo and tinnitus following surgery. This paper compares the effectiveness of MTSS with that of TSS. Methods: The medical records of patients with otosclerosis after stapes surgery (TSS or MTSS were analyzed. Outcome variables included post-operative vertigo, tinnitus, and hearing success. Multivariate logistic regression analysis was used to determine the correlation between surgical technique and outcome variables. Results: TSS was performed in 23 otosclerosis ears and MTSS was performed in 33 otosclerosis ears. The risk of post-operative vertigo was significantly lower among patients that underwent MTSS (27% than among those that underwent TSS (83%, p < 0.001. No differences in the incidence of tinnitus were observed between the two groups. Post-operative audiometric outcomes were also equivalent between the two groups. However, multivariate logistic regression analysis revealed a correlation between post-operative vertigo and surgical technique (p < 0.001. Conclusion: MTSS involves a lower risk of vertigo than does TSS. MTSS helps to prevent damage to the footplate, thereby reducing the risk of footplate floating. Therefore, MTSS provides a means to overcome some of the limitations associated with the narrow surgical field in Asian patients. Keywords: Footplate floating, Minimally traumatic, Otosclerosis, Stapes surgery, Vertigo

Ultrasound-guided transversus abdominis plane block: An evaluation of its efficacy in reducing post-operative opioid requirements in caesarean section

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Shahid Adeel

2017-01-01

Full Text Available Background: Different volumes of local anaesthetic are employed in transversus abdominis plane (TAP block to provide analgesia for lower abdominal surgeries. Our aim was to compare the efficacy of high versus low volume of bupivacaine TAP block in providing postoperative analgesia for caesarean sections. Settings and Design: Prospective, single-blind, randomized comparative study was performed during post-operative period. Materials and Methods: Sixty patients who had received spinal anaesthesia for caesarean section were randomly allocated to one of three groups: Group A received 20 ml of 0.25% bupivacaine, Group B received 30 ml of 0.166% bupivacaine on each side TAP block under ultrasound guidance, respectively, and Group C did not receive TAP block. Multi-modal analgesia comprising paracetamol, diclofenac and patient-controlled analgesia (PCA morphine was administered to all patients. The primary outcome measure in our study was 24-h post-operative morphine consumption through intravenous (IV PCA. Other secondary outcome measures were pain scores, nausea, sedation and patient satisfaction scores. Statistical Analysis: Statistical analysis done using analysis of variance, Fisher's Exact test and Kruskal–Wallis test. Results: Our primary outcome measure of 24-h cumulative PCA morphine consumption was 18.2 ± 6.5, 17.9 ± 8.6 and 19.4 ± 8.4 mg in groups A, B and C, respectively (P = 0.819. In the secondary outcome measures, 100% of study population in group A & B and 95% of group C had pain score of 0-3 on Numerical Rating Scale (P = 1.000 at 24 hr. 19, 15 and17 patients in group A, B and C, respectively, agreed and 1, 5 and 3 patients in group A, B and C, respectively, very strongly agreed with patient satisfaction survey for pain management (P = 0.265. Conclusion: TAP block as a part of multi-modal analgesia is debatable in the context of reducing the need of post-operative opioids. The present study was unequivocal in that two different

The role of pre-operative and post-operative glucose control in surgical-site infections and mortality.

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Christie Y Jeon

Full Text Available The impact of glucose control on surgical-site infection (SSI and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death.This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to analyze how thirty-day risk of SSI and in-hospital death varies by glucose levels and variability. Maximum pre- and post-operative glucose levels were determined for 72 hours before and after the operation and glucose variability was defined as the coefficient of variation of the glucose measurements. We employed logistic regression to model the risk of SSI or death against glucose variables and the following potential confounders: age, sex, body mass index, duration of operation, diabetes status, procedure classification, physical status, emergency status, and blood transfusion.While association of pre- and post-operative hyperglycemia with SSI were apparent in the crude analysis, multivariate results showed that SSI risk did not vary significantly with glucose levels. On the other hand, in-hospital deaths were associated with pre-operative hypoglycemia (OR = 5.09, 95% CI (1.80, 14.4 and glucose variability (OR = 1.14, 95% CI (1.03, 1.27 for 10% increase in coefficient of variation.In-hospital deaths occurred more often among those with pre-operative hypoglycemia and higher glucose variability. These findings warrant further investigation to determine whether stabilization of glucose and prevention of hypoglycemia could reduce post-operative deaths.

The role of pre-operative and post-operative glucose control in surgical-site infections and mortality.

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Jeon, Christie Y; Furuya, E Yoko; Berman, Mitchell F; Larson, Elaine L

2012-01-01

The impact of glucose control on surgical-site infection (SSI) and death remains unclear. We examined how pre- and post-operative glucose levels and their variability are associated with the risk of SSI or in-hospital death. This retrospective cohort study employed data on 13,800 hospitalized patients who underwent a surgical procedure at a large referral hospital in New York between 2006 and 2008. Over 20 different sources of electronic data were used to analyze how thirty-day risk of SSI and in-hospital death varies by glucose levels and variability. Maximum pre- and post-operative glucose levels were determined for 72 hours before and after the operation and glucose variability was defined as the coefficient of variation of the glucose measurements. We employed logistic regression to model the risk of SSI or death against glucose variables and the following potential confounders: age, sex, body mass index, duration of operation, diabetes status, procedure classification, physical status, emergency status, and blood transfusion. While association of pre- and post-operative hyperglycemia with SSI were apparent in the crude analysis, multivariate results showed that SSI risk did not vary significantly with glucose levels. On the other hand, in-hospital deaths were associated with pre-operative hypoglycemia (OR = 5.09, 95% CI (1.80, 14.4)) and glucose variability (OR = 1.14, 95% CI (1.03, 1.27) for 10% increase in coefficient of variation). In-hospital deaths occurred more often among those with pre-operative hypoglycemia and higher glucose variability. These findings warrant further investigation to determine whether stabilization of glucose and prevention of hypoglycemia could reduce post-operative deaths.

Operative Start Time Does Not Affect Post-Operative Infection Risk.

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Guidry, Christopher A; Davies, Stephen W; Willis, Rhett N; Dietch, Zachary C; Shah, Puja M; Sawyer, Robert G

2016-10-01

Surgical care is delivered 24 h a day at most institutions. Alarmingly, some authors have found that certain operative start times are associated with greater morbidity and mortality rates. This effect has been noted in both the public and private sector. Although some of these differences may be related to process, they may also be caused by the human circadian rhythm and corresponding changes in host defenses. We hypothesized that the time of day of an operation would impact the frequency of certain post-operative outcomes significantly. Cases at a single tertiary-care center reported to the American College of Surgeons National Surgical Quality Improvement Program over a 10-year period were identified. Operative start times were divided into six-hour blocks, with 6 am to noon serving as the reference. Standard univariable techniques were applied. Multivariable logistic regression with mixed effects modeling then was used to determine the relation between operative start times and infectious outcomes, controlling for surgeon clustering. Statistical significance was set at p operative infectious complication. Seventy percent of these infections (n = 1,506) were surgical site infections. On univariable analysis considering all cases, nighttime and evening operations had higher rates of post-operative infections than those in performed during the day (9.1% from 6 am to noon; 9.7% from noon to 6 pm; 14.8% from 6 pm to midnight; and 14.4% from midnight to 6 am; p operative start time was not associated with the risk of post-operative infection, even when emergency cases were considered independently. Our data suggest that operative start times have no correlation with post-operative infectious complications. Further work is required to identify the source of the time-dependent outcome variability observed in previous studies.

Complications of rotator cuff surgery—the role of post-operative imaging in patient care

Science.gov (United States)

Thakkar, R S; Thakkar, S C; Srikumaran, U; Fayad, L M

2014-01-01

When pain or disability occurs after rotator cuff surgery, post-operative imaging is frequently performed. Post-operative complications and expected post-operative imaging findings in the shoulder are presented, with a focus on MRI, MR arthrography (MRA) and CT arthrography. MR and CT techniques are available to reduce image degradation secondary to surgical distortions of native anatomy and implant-related artefacts and to define complications after rotator cuff surgery. A useful approach to image the shoulder after surgery is the standard radiography, followed by MRI/MRA for patients with low “metal presence” and CT for patients who have a higher metal presence. However, for the assessment of patients who have undergone surgery for rotator cuff injuries, imaging findings should always be correlated with the clinical presentation because post-operative imaging abnormalities do not necessarily correlate with symptoms. PMID:24734935

Music Therapy for Post Operative Cardiac Patients

DEFF Research Database (Denmark)

Schou, Karin

of participants' self-reporting of anxiety, pain and mood before and after surgery. Data were also collected on length of hospital stay, participants' satisfaction with the hospitalisation, and on participants' intake of analgesic medication. Participants self-reported through questionnaires on the importance...... and after treatment. Conclusion The sample was relatively small reducing the statistical power. However, the results tend to support findings from previous studies that have involved interventions with post-operative patients. Future research should investigate whether GRM would prove beneficial for wider...

Effect of Submucosal Injection of Dexamethasone on Post-operative Sequelae of Third Molar Surgery

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S P Deo

2011-06-01

Full Text Available Introduction: This study was carried out to evaluate the effects of a single pre-operative sub-mucosal injection of dexamethasone after third molar surgery to see the effects on post-operative discomfort. Methods: This study was a prospective, double-blind, randomized, clinical trial. The subjects were forty patients who underwent surgical removal of the mandibular impacted third molar under local anesthesia and after being randomly assigned to receive either an 8 mg dexamethasone as submucosal injection or a normal saline injection into the lower buccal vestibule adjacent to the third molar. The maximum interincisal distance and facial contours were measured at the baseline and post-surgically on Day 2 and 7. Post-operative pain was evaluated subjectively using a visual analog scale and objectively by counting the number of analgesic tablets used. All subjects were operated upon by the same investigator to minimize the difference from inter-operator variability. Results: There was a signicant difference in the measurements of the degree of swelling and trismus between the two groups on the 2nd post-operative day. In contrast, there was no statistically signicant difference between the groups on the 7th post-operative day. The test group also used fewer analgesics post-operatively. Conclusions: Submucosal injection of dexamethasone after third molar surgery is effective in reducing postoperative swelling and trismus. It also delays the onset of post-operative pain. Keywords: dexamethasone, submucosal injection, third molar, third molar surgery, third molar extraction

Treatment with Rutin - A Therapeutic Strategy for Neutrophil-Mediated Inflammatory and Autoimmune Diseases - Anti-inflammatory Effects of Rutin on Neutrophils -

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Bahareh Abd Nikfarjam

2017-03-01

Full Text Available Objectives: Neutrophils represent the front line of human defense against infections. Immediately after stimulation, neutrophilic enzymes are activated and produce toxic mediators such as pro-inflammatory cytokines, nitric oxide (NO and myeloperoxidase (MPO. These mediators can be toxic not only to infectious agents but also to host tissues. Because flavonoids exhibit antioxidant and anti-inflammatory effects, they are subjects of interest for pharmacological modulation of inflammation. In the present study, the effects of rutin on stimulus-induced NO and tumor necrosis factor (TNF-α productions and MPO activity in human neutrophils were investigated. Methods: Human peripheral blood neutrophils were isolated using Ficoll-Hypaque density gradient centrifugation coupled with dextran T500 sedimentation. The cell preparations containing > 98% granulocytes were determined by morphological examination through Giemsa staining. Neutrophils were cultured in complete Roswell Park Memorial Institute (RPMI medium, pre-incubated with or without rutin (25 μM for 45 minutes, and stimulated with phorbol 12-myristate 13-acetate (PMA. Then, the TNF-α, NO and MPO productions were analyzed using enzyme-linked immunosorbent assay (ELISA, Griess Reagent, and MPO assay kits, respectively. Also, the viability of human neutrophils was assessed using tetrazolium salt 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide (MTT, and neutrophils were treated with various concentrations of rutin (1 - 100 μM, after which MTT was appended and incubated at 37ºC for 4 hour. Results: Rutin at concentrations up to 100 μM did not affect neutrophil viability during the 4-hour incubation period. Rutin significantly decreased the NO and TNF-α productions in human peripheral blood neutrophils compared to PMA-control cells (P < 0.001. Also, MPO activity was significantly reduced by rutin (P < 0.001. Conclusion: In this in vitro study, rutin had an anti-inflammatory effect

Neutrophil extracellular traps - the dark side of neutrophils

DEFF Research Database (Denmark)

Sørensen, Ole E.; Borregaard, Niels

2016-01-01

Neutrophil extracellular traps (NETs) were discovered as extracellular strands of decondensed DNA in complex with histones and granule proteins, which were expelled from dying neutrophils to ensnare and kill microbes. NETs are formed during infection in vivo by mechanisms different from those ori...

Gβ1 is required for neutrophil migration in zebrafish.

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Ke, Wenfan; Ye, Ding; Mersch, Kacey; Xu, Hui; Chen, Songhai; Lin, Fang

2017-08-01

Signaling mediated by G protein-coupled receptors (GPCRs) is essential for the migration of cells toward chemoattractants. The recruitment of neutrophils to injured tissues in zebrafish larvae is a useful model for studying neutrophil migration and trafficking in vivo. Indeed, the study of this process led to the discovery that PI3Kγ is required for the polarity and motility of neutrophils, features that are necessary for the directed migration of these cells to wounds. However, the mechanism by which PI3Kγ is activated remains to be determined. Here we show that signaling by specifically the heterotrimeric G protein subunit Gβ1 is critical for neutrophil migration in response to wounding. In embryos treated with small-molecule inhibitors of Gβγ signaling, neutrophils failed to migrate to wound sites. Although both the Gβ1 and Gβ4 isoforms are expressed in migrating neutrophils, only deficiency for the former (morpholino-based knockdown) interfered with the directed migration of neutrophils towards wounds. The Gβ1 deficiency also impaired the ability of cells to change cell shape and reduced their general motility, defects that are similar to those in neutrophils deficient for PI3Kγ. Transplantation assays showed that the requirement for Gβ1 in neutrophil migration is cell autonomous. Finally, live imaging revealed that Gβ1 is required for polarized activation of PI3K, and for the actin dynamics that enable neutrophil migration. Collectively, our data indicate that Gβ1 signaling controls proper neutrophil migration by activating PI3K and modulating actin dynamics. Moreover, they illustrate a role for a specific Gβ isoform in chemotaxis in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Post-operative pain prevalence, predictors, management practices ...

African Journals Online (AJOL)

MWASHAMBWA

developing countries however, the prevalence of post-operative pain is relatively very high and pain control strategies ... Keywords: post-operative pain, prevalence, predictors, pain management, satisfaction, Tanzania. Introduction ..... perception and patterns of cerebral activation during noxious heat stimulation in humans.

Computer-assisted image analysis assay of human neutrophil chemotaxis in vitro

DEFF Research Database (Denmark)

Jensen, P; Kharazmi, A

1991-01-01

We have developed a computer-based image analysis system to measure in-filter migration of human neutrophils in the Boyden chamber. This method is compared with the conventional manual counting techniques. Neutrophils from healthy individuals and from patients with reduced chemotactic activity were....... Another advantage of the assay is that it can be used to show the migration pattern of different populations of neutrophils from both healthy individuals and patients....

Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.

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Yarnitsky, David; Crispel, Yonathan; Eisenberg, Elon; Granovsky, Yelena; Ben-Nun, Alon; Sprecher, Elliot; Best, Lael-Anson; Granot, Michal

2008-08-15

Surgical and medical procedures, mainly those associated with nerve injuries, may lead to chronic persistent pain. Currently, one cannot predict which patients undergoing such procedures are 'at risk' to develop chronic pain. We hypothesized that the endogenous analgesia system is key to determining the pattern of handling noxious events, and therefore testing diffuse noxious inhibitory control (DNIC) will predict susceptibility to develop chronic post-thoracotomy pain (CPTP). Pre-operative psychophysical tests, including DNIC assessment (pain reduction during exposure to another noxious stimulus at remote body area), were conducted in 62 patients, who were followed 29.0+/-16.9 weeks after thoracotomy. Logistic regression revealed that pre-operatively assessed DNIC efficiency and acute post-operative pain intensity were two independent predictors for CPTP. Efficient DNIC predicted lower risk of CPTP, with OR 0.52 (0.33-0.77 95% CI, p=0.0024), i.e., a 10-point numerical pain scale (NPS) reduction halves the chance to develop chronic pain. Higher acute pain intensity indicated OR of 1.80 (1.28-2.77, p=0.0024) predicting nearly a double chance to develop chronic pain for each 10-point increase. The other psychophysical measures, pain thresholds and supra-threshold pain magnitudes, did not predict CPTP. For prediction of acute post-operative pain intensity, DNIC efficiency was not found significant. Effectiveness of the endogenous analgesia system obtained at a pain-free state, therefore, seems to reflect the individual's ability to tackle noxious events, identifying patients 'at risk' to develop post-intervention chronic pain. Applying this diagnostic approach before procedures that might generate pain may allow individually tailored pain prevention and management, which may substantially reduce suffering.

Targeting neutrophilic inflammation in severe neutrophilic asthma : can we target the disease-relevant neutrophil phenotype?

NARCIS (Netherlands)

Bruijnzeel, Piet L B; Uddin, Mohib; Koenderman, Leo

2015-01-01

In severe, neutrophilic asthma, neutrophils are thought to have an important role in both the maintenance of the disease and during exacerbations. These patients often display excessive, mucosal airway inflammation with unresolving neutrophilia. Because this variant of asthma is poorly controlled by

Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

Science.gov (United States)

Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

2006-09-15

Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

A Neutrophil Phenotype Model for Extracorporeal Treatment of Sepsis.

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Alexander D Malkin

2015-10-01

Full Text Available Neutrophils play a central role in eliminating bacterial pathogens, but may also contribute to end-organ damage in sepsis. Interleukin-8 (IL-8, a key modulator of neutrophil function, signals through neutrophil specific surface receptors CXCR-1 and CXCR-2. In this study a mechanistic computational model was used to evaluate and deploy an extracorporeal sepsis treatment which modulates CXCR-1/2 levels. First, a simplified mechanistic computational model of IL-8 mediated activation of CXCR-1/2 receptors was developed, containing 16 ODEs and 43 parameters. Receptor level dynamics and systemic parameters were coupled with multiple neutrophil phenotypes to generate dynamic populations of activated neutrophils which reduce pathogen load, and/or primed neutrophils which cause adverse tissue damage when misdirected. The mathematical model was calibrated using experimental data from baboons administered a two-hour infusion of E coli and followed for a maximum of 28 days. Ensembles of parameters were generated using a Bayesian parallel tempering approach to produce model fits that could recreate experimental outcomes. Stepwise logistic regression identified seven model parameters as key determinants of mortality. Sensitivity analysis showed that parameters controlling the level of killer cell neutrophils affected the overall systemic damage of individuals. To evaluate rescue strategies and provide probabilistic predictions of their impact on mortality, time of onset, duration, and capture efficacy of an extracorporeal device that modulated neutrophil phenotype were explored. Our findings suggest that interventions aiming to modulate phenotypic composition are time sensitive. When introduced between 3-6 hours of infection for a 72 hour duration, the survivor population increased from 31% to 40-80%. Treatment efficacy quickly diminishes if not introduced within 15 hours of infection. Significant harm is possible with treatment durations ranging from 5

Intra-operative colloid administration increases the clearance of a post-operative fluid load

DEFF Research Database (Denmark)

Borup, Tine; Hahn, Robert; Holte, K

2009-01-01

using volume kinetics based on the plasma dilution alone. The pre-operative plasma clearance was compared with the post-operative plasma clearance and patients served as their own control. RESULTS: The urinary excretion averaged 350 ml for the pre-operative infusion and 612 ml post-operatively, which...

Formation of neutrophil extracellular traps under low oxygen level

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Katja Branitzki-Heinemann

2016-11-01

Full Text Available Since their discovery, neutrophil extracellular traps (NETs have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia inducible factor 1α (HIF-1α by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps. Since HIF-1α is a global regulator of the cellular response to low oxygen, we hypothesized that NET formation may be similarly increased under low oxygen conditions. Hypoxia occurs in tissues during infection or inflammation, mostly due to overconsumption of oxygen by pathogens and recruited immune cells. Therefore, experiments were performed to characterize the formation of NETs under hypoxic oxygen conditions compared to normoxia. Human blood-derived neutrophils were isolated and incubated under normoxic (21% oxygen level and compared to hypoxic (1% conditions. Dissolved oxygen levels were monitored in the primary cell culture using a Fibox4-PSt3 measurement system. The formation of NETs was quantified by fluorescence microscopy in response to the known NET-inducer phorbol 12-myristate 13-acetate (PMA or S. aureus wildtype and a nuclease-deficient mutant. In contrast to our hypothesis, spontaneous NET formation of neutrophils incubated under hypoxia was distinctly reduced compared to control neutrophils incubated under normoxia. Furthermore, neutrophils incubated under hypoxia showed significantly reduced formation of NETs in response to PMA. Gene expression analysis revealed that mRNA level of hif-1α as well as hif-1α target genes was not altered. However, in good correlation to the decreased NET formation under hypoxia, the cholesterol content of the neutrophils was

Evasion of Human Neutrophil-Mediated Host Defense during Toxoplasma gondii Infection.

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Lima, Tatiane S; Gov, Lanny; Lodoen, Melissa B

2018-02-13

Neutrophils are a major player in host immunity to infection; however, the mechanisms by which human neutrophils respond to the intracellular protozoan parasite Toxoplasma gondii are still poorly understood. In the current study, we found that, whereas primary human monocytes produced interleukin-1beta (IL-1β) in response to T. gondii infection, human neutrophils from the same blood donors did not. Moreover, T. gondii inhibited lipopolysaccharide (LPS)-induced IL-1β synthesis in human peripheral blood neutrophils. IL-1β suppression required active parasite invasion, since heat-killed or mycalolide B-treated parasites did not inhibit IL-1β release. By investigating the mechanisms involved in this process, we found that T. gondii infection of neutrophils treated with LPS resulted in reduced transcript levels of IL-1β and NLRP3 and reduced protein levels of pro-IL-1β, mature IL-1β, and the inflammasome sensor NLRP3. In T. gondii -infected neutrophils stimulated with LPS, the levels of MyD88, TRAF6, IKKα, IKKβ, and phosphorylated IKKα/β were not affected. However, LPS-induced IκBα degradation and p65 phosphorylation were reduced in T. gondii- infected neutrophils, and degradation of IκBα was reversed by treatment with the proteasome inhibitor MG-132. Finally, we observed that T. gondii inhibited the cleavage and activity of caspase-1 in human neutrophils. These results indicate that T. gondii suppression of IL-1β involves a two-pronged strategy whereby T. gondii inhibits both NF-κB signaling and activation of the NLRP3 inflammasome. These findings represent a novel mechanism of T. gondii evasion of human neutrophil-mediated host defense by targeting the production of IL-1β. IMPORTANCE Toxoplasma gondii is an obligate intracellular parasite that infects approximately one-third of humans worldwide and can invade virtually any nucleated cell in the human body. Although it is well documented that neutrophils infiltrate the site of acute T

d(− Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

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Pablo Alarcón

2017-08-01

Full Text Available Bovine ruminal acidosis is of economic importance as it contributes to reduced milk and meat production. This phenomenon is mainly attributed to an overload of highly fermentable carbohydrate, resulting in increased d(− lactic acid levels in serum and plasma. Ruminal acidosis correlates with elevated acute phase proteins in blood, along with neutrophil activation and infiltration into various tissues leading to laminitis and aseptic polysynovitis. Previous studies in bovine neutrophils indicated that d(− lactic acid decreased expression of L-selectin and increased expression of CD11b to concentrations higher than 6 mM, suggesting a potential role in neutrophil adhesion onto endothelia. The two aims of this study were to evaluate whether d(− lactic acid influenced neutrophil and endothelial adhesion and to trigger neutrophil extracellular trap (NET production (NETosis in exposed neutrophils. Exposure of bovine neutrophils to 5 mM d(− lactic acid elevated NET release compared to unstimulated neutrophil negative controls. Moreover, this NET contains CD11b and histone H4 citrullinated, the latter was dependent on PAD4 activation, a critical enzyme in DNA decondensation and NETosis. Furthermore, NET formation was dependent on d(− lactic acid plasma membrane transport through monocarboxylate transporter 1 (MCT1. d(− lactic acid enhanced neutrophil adhesion onto endothelial sheets as demonstrated by in vitro neutrophil adhesion assays under continuous physiological flow conditions, indicating that cell adhesion was a NET- and a CD11b/ICAM-1-dependent process. Finally, d(− lactic acid was demonstrated for the first time to trigger NETosis in a PAD4- and MCT1-dependent manner. Thus, d(− lactic acid-mediated neutrophil activation may contribute to neutrophil-derived pro-inflammatory processes, such as aseptic laminitis and/or polysynovitis in animals suffering acute ruminal acidosis.

Circumventing Y. pestis Virulence by Early Recruitment of Neutrophils to the Lungs during Pneumonic Plague.

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Yaron Vagima

2015-05-01

Full Text Available Pneumonic plague is a fatal disease caused by Yersinia pestis that is associated with a delayed immune response in the lungs. Because neutrophils are the first immune cells recruited to sites of infection, we investigated the mechanisms responsible for their delayed homing to the lung. During the first 24 hr after pulmonary infection with a fully virulent Y. pestis strain, no significant changes were observed in the lungs in the levels of neutrophils infiltrate, expression of adhesion molecules, or the expression of the major neutrophil chemoattractants keratinocyte cell-derived chemokine (KC, macrophage inflammatory protein 2 (MIP-2 and granulocyte colony stimulating factor (G-CSF. In contrast, early induction of chemokines, rapid neutrophil infiltration and a reduced bacterial burden were observed in the lungs of mice infected with an avirulent Y. pestis strain. In vitro infection of lung-derived cell-lines with a YopJ mutant revealed the involvement of YopJ in the inhibition of chemoattractants expression. However, the recruitment of neutrophils to the lungs of mice infected with the mutant was still delayed and associated with rapid bacterial propagation and mortality. Interestingly, whereas KC, MIP-2 and G-CSF mRNA levels in the lungs were up-regulated early after infection with the mutant, their protein levels remained constant, suggesting that Y. pestis may employ additional mechanisms to suppress early chemoattractants induction in the lung. It therefore seems that prevention of the early influx of neutrophils to the lungs is of major importance for Y. pestis virulence. Indeed, pulmonary instillation of KC and MIP-2 to G-CSF-treated mice infected with Y. pestis led to rapid homing of neutrophils to the lung followed by a reduction in bacterial counts at 24 hr post-infection and improved survival rates. These observations shed new light on the virulence mechanisms of Y. pestis during pneumonic plague, and have implications for the

Hydrogen sulfide reduces neutrophil recruitment in hind-limb ischemia-reperfusion injury in an L-selectin and ADAM-17 dependent manner

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Ball, Carissa J.; Reiffel, Alyssa J.; Chintalapani, Sathvika; Kim, Minsoo; Spector, Jason A.; King, Michael R.

2012-01-01

Background Reperfusion following ischemia leads to neutrophil recruitment injured tissue. Selectins and β2 integrins regulate neutrophil interaction with the endothelium during neutrophil rolling and firm adhesion. Excessive neutrophil infiltration into tissue is thought to contribute to IRI damage. NaHS mitigates the damage caused by ischemia-reperfusion injury (IRI). This study's objective was to determine the effect of hydrogen sulfide (NaHS) on neutrophil adhesion receptor expression. Methods Human neutrophils were either left untreated or incubated in 20 μM NaHS, and/or 50 μg/mL pharmacological ADAM-17 inhibitor TAPI-0; activated by IL-8, fMLP, or TNF-α; and labeled against PSGL-1, LFA-1, Mac-1 α, L-selectin and β2 integrin epitopes CBRM1/5 or KIM127 for flow cytometry. Cohorts of 3 C57BL/6 mice received an intravenous dose of saline vehicle, or 20 μM NaHS with or without 50 μg/mL TAPI-0 before unilateral tourniquet induced hind-limb ischemia for 3 hours followed by 3 hours of reperfusion. Bilateral gastrocnemius muscles were processed for histology before neutrophil infiltration quantification. Results NaHS treatment significantly increased L-selectin shedding from human neutrophils following activation by fMLP and IL-8 in an ADAM-17 dependent manner. Mice treated with NaHS to raise bloodstream concentration by 20 μM prior to ischemia or reperfusion showed a significant reduction in neutrophil recruitment into skeletal muscle tissue following tourniquet-induced hindlimb IRI. Conclusions NaHS administration results in the downregulation of L-selectin expression in activated human neutrophils. This leads to a reduction in neutrophil extravasation and tissue infiltration and may partially account for the protective effects of NaHS seen in the setting of IRI. PMID:23446563

Association between elevated pre-operative glycosylated hemoglobin and post-operative infections after non-emergent surgery

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Joseph M. Blankush

2016-09-01

Conclusions: The risk factors of post-operative infection are multiple and likely synergistic. While pre-operative HbA1c level is not independently associated with risk of post-operative infection, there are scenarios and patient subgroups where pre-operative HbA1c is useful in predicting an increased risk of infectious complications in the post-operative period.

The Natural Stilbenoid Piceatannol Decreases Activity and Accelerates Apoptosis of Human Neutrophils: Involvement of Protein Kinase C

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Viera Jancinova

2013-01-01

Full Text Available Neutrophils are able to release cytotoxic substances and inflammatory mediators, which, along with their delayed apoptosis, have a potential to maintain permanent inflammation. Therefore, treatment of diseases associated with chronic inflammation should be focused on neutrophils; formation of reactive oxygen species and apoptosis of these cells represent two promising targets for pharmacological intervention. Piceatannol, a naturally occurring stilbenoid, has the ability to reduce the toxic action of neutrophils. This substance decreased the amount of oxidants produced by neutrophils both extra- and intracellularly. Radicals formed within neutrophils (fulfilling a regulatory role were reduced to a lesser extent than extracellular oxidants, potentially dangerous for host tissues. Moreover, piceatannol did not affect the phosphorylation of p40phox—a component of NADPH oxidase, responsible for the assembly of functional oxidase in intracellular (granular membranes. The stilbenoid tested elevated the percentage of early apoptotic neutrophils, inhibited the activity of protein kinase C (PKC—the main regulatory enzyme in neutrophils, and reduced phosphorylation of PKC isoforms α, βII, and δ on their catalytic region. The results indicated that piceatannol may be useful as a complementary medicine in states associated with persisting neutrophil activation and with oxidative damage of tissues.

Chronic Prosopis Glandulosa Treatment Blunts Neutrophil Infiltration and Enhances Muscle Repair after Contusion Injury

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Cindy George

2015-01-01

Full Text Available The current treatment options for soft tissue injuries remain suboptimal and often result in delayed/incomplete recovery of damaged muscle. The current study aimed to evaluate the effects of oral Prosopis glandulosa treatment on inflammation and regeneration in skeletal muscle after contusion injury, in comparison to a conventional treatment. The gastrocnemius muscle of rats was subjected to mass-drop injury and muscle samples collected after 1-, 3 h, 1- and 7 days post-injury. Rats were treated with P. glandulosa (100 mg/kg/day either for 8 weeks prior to injury (up until day 7 post-injury, only post-injury, or with topically applied diclofenac post-injury (0.57 mg/kg. Neutrophil (His48-positive and macrophage (F4/80-positive infiltration was assessed by means of immunohistochemistry. Indicators of muscle satellite cell proliferation (ADAM12 and regeneration (desmin were used to evaluate muscle repair. Chronic P. glandulosa and diclofenac treatment (p < 0.0001 was associated with suppression of the neutrophil response to contusion injury, however only chronic P. glandulosa treatment facilitated more effective muscle recovery (increased ADAM12 (p < 0.05 and desmin (p < 0.001 expression, while diclofenac treatment had inhibitory effects on repair, despite effective inhibition of neutrophil response. Data indicates that P. glandulosa treatment results in more effective muscle repair after contusion.

[Post-operative infections after cosmetic tourism].

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Holst-Albrechtsen, Sine; Sørensen, Lene Birk; Juel, Jacob

2018-06-11

Cosmetic tourism is defined as patient mobility across borders, typically constituted by patients seeking cosmetic surgery at lower costs abroad. The most common procedures are abdominoplasty, fat grafting and breast augmentation. Very little is known about the complication rates after cosmetic tourism, and there is a paucity of evidence in all aspects of cosmetic tourism. In this review, we focus on post-operative complications i.e. post-operative infections, in particular with rare microorganisms such as mycobacteria.

Hyperglycemia Impairs Neutrophil-Mediated Bacterial Clearance in Mice Infected with the Lyme Disease Pathogen.

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Ashkan Javid

Full Text Available Insulin-insufficient type 1 diabetes is associated with attenuated bactericidal function of neutrophils, which are key mediators of innate immune responses to microbes as well as pathological inflammatory processes. Neutrophils are central to immune responses to the Lyme pathogen Borrelia burgdorferi. The effect of hyperglycemia on host susceptibility to and outcomes of B. burgdorferi infection has not been examined. The present study investigated the impact of sustained obesity-independent hyperglycemia in mice on bacterial clearance, inflammatory pathology and neutrophil responses to B. burgdorferi. Hyperglycemia was associated with reduced arthritis incidence but more widespread tissue colonization and reduced clearance of bacterial DNA in multiple tissues including brain, heart, liver, lung and knee joint. B. burgdorferi uptake and killing were impaired in neutrophils isolated from hyperglycemic mice. Thus, attenuated neutrophil function in insulin-insufficient hyperglycemia was associated with reduced B. burgdorferi clearance in target organs. These data suggest that investigating the effects of comorbid conditions such as diabetes on outcomes of B. burgdorferi infections in humans may be warranted.

MRI characteristics of torn and untorn post-operative menisci

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Kijowski, Richard; Rosas, Humberto; Liu, Fang [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States); Williams, Adam [Radiology and Imaging Consultants, Colorado Springs (United States)

2017-10-15

To compare magnetic resonance imaging (MRI) characteristics of torn and untorn post-operative menisci. The study group consisted of 140 patients with 148 partially resected menisci who were evaluated with a repeat knee MRI examination and subsequent repeat arthroscopic knee surgery. Two musculoskeletal radiologists retrospectively assessed the following MRI characteristics of the post-operative meniscus: contour (smooth or irregular), T2 line through the meniscus (no line, intermediate signal line, intermediate-to-high signal line, and high fluid-like signal line), displaced meniscus fragment, and change in signal pattern through the meniscus compared with baseline MRI. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using arthroscopy as the reference standard. All 36 post-operative menisci with no T2 line were untorn at surgery (100% NPV), whereas 46 of the 79 post-operative menisci with intermediate T2 line, 16 of the 18 post-operative menisci with intermediate-to-high T2 line, and 14 of the 15 post-operative menisci with high T2 line were torn at surgery (58.2%, 88.9%, and 93.3% PPV respectively). Additional MRI characteristics associated with torn post-operative meniscus at surgery were irregular meniscus contour (PPV 85.7%), displaced meniscus fragment (PPV 100%), and change in signal pattern through the meniscus (PPV 99.4%). Post-operative menisci with no T2 signal line were untorn at surgery. The most useful MRI characteristics for predicting torn post-operative menisci at surgery were change in signal pattern through the meniscus compared with baseline MRI, and displaced meniscus fragment followed by high T2 line through the meniscus, intermediate-to-high T2 line through the meniscus, and irregular meniscus contour. (orig.)

MRI characteristics of torn and untorn post-operative menisci

International Nuclear Information System (INIS)

Kijowski, Richard; Rosas, Humberto; Liu, Fang; Williams, Adam

2017-01-01

To compare magnetic resonance imaging (MRI) characteristics of torn and untorn post-operative menisci. The study group consisted of 140 patients with 148 partially resected menisci who were evaluated with a repeat knee MRI examination and subsequent repeat arthroscopic knee surgery. Two musculoskeletal radiologists retrospectively assessed the following MRI characteristics of the post-operative meniscus: contour (smooth or irregular), T2 line through the meniscus (no line, intermediate signal line, intermediate-to-high signal line, and high fluid-like signal line), displaced meniscus fragment, and change in signal pattern through the meniscus compared with baseline MRI. Positive predictive values (PPV) and negative predictive values (NPV) were calculated using arthroscopy as the reference standard. All 36 post-operative menisci with no T2 line were untorn at surgery (100% NPV), whereas 46 of the 79 post-operative menisci with intermediate T2 line, 16 of the 18 post-operative menisci with intermediate-to-high T2 line, and 14 of the 15 post-operative menisci with high T2 line were torn at surgery (58.2%, 88.9%, and 93.3% PPV respectively). Additional MRI characteristics associated with torn post-operative meniscus at surgery were irregular meniscus contour (PPV 85.7%), displaced meniscus fragment (PPV 100%), and change in signal pattern through the meniscus (PPV 99.4%). Post-operative menisci with no T2 signal line were untorn at surgery. The most useful MRI characteristics for predicting torn post-operative menisci at surgery were change in signal pattern through the meniscus compared with baseline MRI, and displaced meniscus fragment followed by high T2 line through the meniscus, intermediate-to-high T2 line through the meniscus, and irregular meniscus contour. (orig.)

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery.

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Chowdhary, Mudit; Switchenko, Jeffrey M; Press, Robert H; Jhaveri, Jaymin; Buchwald, Zachary S; Blumenfeld, Philip A; Marwaha, Gaurav; Diaz, Aidnag; Wang, Dian; Abrams, Ross A; Olson, Jeffrey J; Shu, Hui-Kuo G; Curran, Walter J; Patel, Kirtesh R

2018-05-30

Neutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM). BM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan-Meier method and cumulative incidence with competing risk for death, respectively. 188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03-2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30-2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes. Post-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

Chemokine receptor Ccr1 drives neutrophil-mediated kidney immunopathology and mortality in invasive candidiasis.

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Michail S Lionakis

Full Text Available Invasive candidiasis is the 4(th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1(lo to Ccr1(high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1(+/+ and Ccr1(-/- donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1(+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1(+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang; Zhang, Huoming; Guo, Tiannan; Li, Wenying; Li, Huiyu; Zhu, Yi; Huang, Shiang

2014-01-01

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative proteomics reveals differential biological processes in healthy neonatal cord neutrophils and adult neutrophils

KAUST Repository

Zhu, Jiang

2014-06-11

Neonatal neutrophils are characterized by the immaturity of bactericidal mechanisms that contributes largely to neonatal mortality. However, underlying molecular mechanism associated with the immaturity remains incompletely understood. In this study, we performed comparative proteomic analysis on neonatal neutrophils derived from human cord blood and adult peripheral neutrophils. A total of 1332 proteins were identified and quantified, and 127 proteins were characterized as differentially expressed between adult and cord neutrophils. The differentially expressed proteins are mapped in KEGG pathways into five clusters and indicated impaired functions of neonatal neutrophils in proteasome, lysosome, phagosome, and leukocyte transendothelial migration. In particular, many proteins associated with NETosis, a critical mechanism for antimicrobial process and auto-clearance, were also found to be downregulated in cord neutrophils. This study represents a first comparative proteome profiling of neonatal and adult neutrophils, and provides a global view of differentially expressed proteome for enhancing our understanding of their various functional difference. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

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Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

2017-07-01

Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

A journey to zero: reduction of post-operative cesarean surgical site infections over a five-year period.

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Hickson, Evelyn; Harris, Jeanette; Brett, David

2015-04-01

Surgical site infections (SSI) are a substantial concern for cesarean deliveries in which a surgical site complication is most unwelcome for a mother with a new infant. Steps taken pre- and post-operatively to reduce the number of complications may be of substantial benefit clinically, economically, and psychologically. A risk-based approach to incision management was developed and implemented for all cesarean deliveries at our institution. A number of incremental interventions for low-risk and high-risk patients including pre-operative skin preparations, standardized pre- and post-operative protocols, post-operative nanocrystalline silver anti-microbial barrier dressings, and incisional negative pressure wound therapy (NPWT) were implemented sequentially over a 5-y period. A systematic clinical chart review of 4,942 patients spanning all cesarean deliveries between 2007-2012 was performed to determine what effects the interventions had on the rate of SSI for cesarean deliveries. The percentage of SSI was reduced from 2.13% (2007) to 0.10% (2012) (poperative SSIs were avoided: A total cost saving of nearly $5,000,000. Applying a clinical algorithm for assessing the risk of surgical site complication and making recommendations on pre-operative and post-operative incision management can result in a substantial and sustainable reduction in cesarean SSI.

Oral neutrophil responses to acute prolonged exercise may not be representative of blood neutrophil responses.

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Davison, Glen; Jones, Arwel Wyn

2015-03-01

Neutrophil numbers and function (oxidative burst) were assessed in peripheral blood and oral samples before and after prolonged exercise. Blood neutrophil count increased (∼3.5-fold, P < 0.001) and function decreased (30% ± 19% decrease, P = 0.005) postexercise. Oral neutrophil count (P = 0.392) and function (P = 0.334) were unchanged. Agreement between oral and blood neutrophil function responses to exercise was poor. These findings highlight the importance of studying neutrophils within various compartments/sample types.

Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.

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Zhou, Yebin; Wu, Jianming; Kucik, Dennis F; White, Nathan B; Redden, David T; Szalai, Alexander J; Bullard, Daniel C; Edberg, Jeffrey C

2013-11-01

Multiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1. Neutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry. Mac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation. The nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE

Yersinia pestis targets neutrophils via complement receptor 3

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Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

2015-01-01

Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

Autophagy Mediates Interleukin-1β Secretion in Human Neutrophils

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Leonardo Iula

2018-02-01

Full Text Available Interleukin-1β (IL-1β, a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions. Here, we analyzed if an unconventional secretory autophagy mechanism is involved in the exportation of IL-1β by these cells. Our findings indicated that inhibition of autophagy with 3-methyladenine and Wortmannin markedly reduced IL-1β secretion induced by LPS + ATP, as did the disruption of the autophagic flux with Bafilomycin A1 and E64d. These compounds did not noticeable affect neutrophil viability ruling out that the effects on IL-1β secretion were due to cell death. Furthermore, VPS34IN-1, a specific autophagy inhibitor, was still able to reduce IL-1β secretion when added after it was synthesized. Moreover, siRNA-mediated knockdown of ATG5 markedly reduced IL-1β secretion in neutrophil-differentiated PLB985 cells. Upon LPS + ATP stimulation, IL-1β was incorporated to an autophagic compartment, as was revealed by its colocalization with LC3B by confocal microscopy. Overlapping of IL-1β-LC3B in a vesicular compartment peaked before IL-1β increased in culture supernatants. On the other hand, stimulation of autophagy by cell starvation augmented the colocalization of IL-1β and LC3B and then promoted neutrophil IL-1β secretion. In addition, specific ELISAs indicated that although both IL-1β and pro-IL-1β are released to culture supernatants upon neutrophil stimulation, autophagy only promotes IL-1β secretion. Furthermore, the serine proteases inhibitor

Association between elevated pre-operative glycosylated hemoglobin and post-operative infections after non-emergent surgery.

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Blankush, Joseph M; Leitman, I Michael; Soleiman, Aron; Tran, Trung

2016-09-01

A chronic state of impaired glucose metabolism affects multiple components of the immune system, possibly leading to an increased incidence of post-operative infections. Such infections increase morbidity, length of stay, and overall cost. This study evaluates the correlation between elevated pre-operative glycosylated hemoglobin (HbA1c) and post-operative infections. Adult patients undergoing non-emergent procedures across all surgical subspecialties from January 2010 to July 2014 had a preoperative HbA1c measured as part of their routine pre-surgical assessment. 2200 patient charts (1100 operative infection (superficial surgical site infection, deep wound/surgical space abscess, pneumonia, and/or urinary tract infection as defined by Centers for Disease Control criteria) within 30 days of surgery. Patients with HbA1c infection rate (3.8% in the HbA1c infection. Elevated HbA1c was, however, predictive of significantly increased risk of post-operative infection when associated with increased age (≥81 years of age) or dirty wounds. The risk factors of post-operative infection are multiple and likely synergistic. While pre-operative HbA1c level is not independently associated with risk of post-operative infection, there are scenarios and patient subgroups where pre-operative HbA1c is useful in predicting an increased risk of infectious complications in the post-operative period.

Chemokine Receptor Ccr1 Drives Neutrophil-Mediated Kidney Immunopathology and Mortality in Invasive Candidiasis

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Lionakis, Michail S.; Swamydas, Muthulekha; Wan, Wuzhou; Richard Lee, Chyi-Chia; Cohen, Jeffrey I.; Scheinberg, Phillip; Gao, Ji-Liang; Murphy, Philip M.

2012-01-01

Invasive candidiasis is the 4th leading cause of nosocomial bloodstream infection in the US with mortality that exceeds 40% despite administration of antifungal therapy; neutropenia is a major risk factor for poor outcome after invasive candidiasis. In a fatal mouse model of invasive candidiasis that mimics human bloodstream-derived invasive candidiasis, the most highly infected organ is the kidney and neutrophils are the major cellular mediators of host defense; however, factors regulating neutrophil recruitment have not been previously defined. Here we show that mice lacking chemokine receptor Ccr1, which is widely expressed on leukocytes, had selectively impaired accumulation of neutrophils in the kidney limited to the late phase of the time course of the model; surprisingly, this was associated with improved renal function and survival without affecting tissue fungal burden. Consistent with this, neutrophils from wild-type mice in blood and kidney switched from Ccr1lo to Ccr1high at late time-points post-infection, when Ccr1 ligands were produced at high levels in the kidney and were chemotactic for kidney neutrophils ex vivo. Further, when a 1∶1 mixture of Ccr1+/+ and Ccr1−/− donor neutrophils was adoptively transferred intravenously into Candida-infected Ccr1+/+ recipient mice, neutrophil trafficking into the kidney was significantly skewed toward Ccr1+/+ cells. Thus, neutrophil Ccr1 amplifies late renal immunopathology and increases mortality in invasive candidiasis by mediating excessive recruitment of neutrophils from the blood to the target organ. PMID:22916017

d(−) Lactic Acid-Induced Adhesion of Bovine Neutrophils onto Endothelial Cells Is Dependent on Neutrophils Extracellular Traps Formation and CD11b Expression

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Pablo Alarcón; Carolina Manosalva; Carolina Manosalva; Ivan Conejeros; María D. Carretta; Tamara Muñoz-Caro; Liliana M. R. Silva; Anja Taubert; Carlos Hermosilla; María A. Hidalgo; Rafael A. Burgos

2017-01-01

Bovine ruminal acidosis is of economic importance as it contributes to reduced milk and meat production. This phenomenon is mainly attributed to an overload of highly fermentable carbohydrate, resulting in increased d(−) lactic acid levels in serum and plasma. Ruminal acidosis correlates with elevated acute phase proteins in blood, along with neutrophil activation and infiltration into various tissues leading to laminitis and aseptic polysynovitis. Previous studies in bovine neutrophils indic...

Post-operative telephone review is cost-effective and acceptable to patients.

LENUS (Irish Health Repository)

Gray, R T

2012-02-01

INTRODUCTION: Patients undergoing selective minor emergency and elective procedures are followed up by a nurse-led structured telephone review six weeks post-operatively in our hospital. Our study objectives were to review patients\\' satisfaction, assess cost-effectiveness and compare our practice with other surgical units in Northern Ireland (NI). PATIENTS AND METHODS: Completed telephone follow-up forms were reviewed retrospectively for a three-year period and cost savings calculated. Fifty patients were contacted prospectively by telephone using a questionnaire to assess satisfaction of this follow-up. A postal questionnaire was sent to 68 general and vascular surgeons in NI, assessing individual preferences for patient follow-up. RESULTS: A total of 1378 patients received a telephone review from September 2005 to September 2008. One thousand one hundred and seventy-seven (85.4%) were successfully contacted, while 201 (14.6%) did not respond despite multiple attempts. One hundred and forty-seven respondents (10.7%) required further outpatient follow-up, thereby saving 1231 outpatient reviews, equivalent to pound41,509 per annum. Thirty-nine (78%) patients expected post-operative follow-up, with 29 (58%) expecting this in the outpatient department. However, all patients were satisfied with the nurse-led telephone review. Fifty-three (78%) consultants responded. Those who always, or occasionally, review patients post-operatively varies according to the operation performed, ranging from 2.2% appendicectomy patients to 40.0% for varicose vein surgery. CONCLUSION: Current practice in NI varies, but a significant proportion of patients are not routinely reviewed. This study confirmed that patients expect post-operative follow-up. A nurse-led telephone review service is acceptable to patients, cost-effective and reduces the number of unnecessary outpatient reviews.

Prophylactic post-operative radiotherapy prevents heterotopic ossification following traumatic acetabular fracture

International Nuclear Information System (INIS)

Meyer, Joseph T.; Hixson, William C.; Jennelle, Richard L. S.; Alonso, Jorge E.; Raben, David; Spencer, Sharon S.; Kim, Robert Y.

1996-01-01

(6))) of patients receiving 1000 cGy/5 fxs developed heterotopic ossification, while 7% ((2(26))) and 0% ((0(2))) receiving 700 cGy/1 fx and 800 cGy/1 fx developed heterotopic ossification, respectively. In patients with and without heterotopic ossification, the mean injury-to-radiation interval was 23.2 and 7.8 days and the surgery-to-radiation interval was 6.6 and 2.2 days, respectively. Conclusion: Prophylactic post-operative radiotherapy following traumatic acetabular fracture significantly reduces the incidence of heterotopic ossification. Radiation dose, surgery-to-radiation interval, and as yet unrecognized, injury-to-radiation interval are related to the development of heterotopic ossification

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

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Knight, Jason S.; Meng, He; Coit, Patrick; Yalavarthi, Srilakshmi; Sule, Gautam; Gandhi, Alex A.; Grenn, Robert C.; Mazza, Levi F.; Ali, Ramadan A.; Renauer, Paul; Wren, Jonathan D.; Bockenstedt, Paula L.; Wang, Hui; Eitzman, Daniel T.; Sawalha, Amr H.

2017-01-01

Antiphospholipid antibodies, present in one-third of lupus patients, increase the risk of thrombosis. We recently reported a key role for neutrophils — neutrophil extracellular traps (NETs), in particular — in the thrombotic events that define antiphospholipid syndrome (APS). To further elucidate the role of neutrophils in APS, we performed a comprehensive transcriptome analysis of neutrophils isolated from patients with primary APS. Moreover, APS-associated venous thrombosis was modeled by treating mice with IgG prepared from APS patients, followed by partial restriction of blood flow through the inferior vena cava. In patients, APS neutrophils demonstrated a proinflammatory signature with overexpression of genes relevant to IFN signaling, cellular defense, and intercellular adhesion. For in vivo studies, we focused on P-selectin glycoprotein ligand-1 (PSGL-1), a key adhesion molecule overexpressed in APS neutrophils. The introduction of APS IgG (as compared with control IgG) markedly potentiated thrombosis in WT mice, but not PSGL-1–KOs. PSGL-1 deficiency was also associated with reduced leukocyte vessel wall adhesion and NET formation. The thrombosis phenotype was restored in PSGL-1–deficient mice by infusion of WT neutrophils, while an anti–PSGL-1 monoclonal antibody inhibited APS IgG–mediated thrombosis in WT mice. PSGL-1 represents a potential therapeutic target in APS. PMID:28931754

Urinary tract infections and post-operative fever in percutaneous nephrolithotomy.

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Gutierrez, Jorge; Smith, Arthur; Geavlete, Petrisor; Shah, Hemendra; Kural, Ali Riza; de Sio, Marco; Amón Sesmero, José H; Hoznek, András; de la Rosette, Jean

2013-10-01

To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre-operative urine samples and who received antibiotic prophylaxis were included. Pre-operative bladder urine culture and post-operative fever (>38.5°C) were assessed. Relationship between various patient and operative factors and occurrence of post-operative fever was assessed using logistic regression analyses. Eight hundred and sixty-five (16.2%) patients had a positive urine culture; Escherichia coli was the most common micro-organism found in urine of the 350 patients (6.5%). Of the patients with negative pre-operative urine cultures, 8.8% developed a fever post-PCNL, in contrast to 18.2% of patients with positive urine cultures. Fever developed more often among the patients whose urine cultures consisted of Gram-negative micro-organisms (19.4-23.8%) versus those with Gram-positive micro-organisms (9.7-14.5%). Multivariate analysis indicated that a positive urine culture (odds ratio [OR] = 2.12, CI [1.69-2.65]), staghorn calculus (OR = 1.59, CI [1.28-1.96]), pre-operative nephrostomy (OR = 1.61, CI [1.19-2.17]), lower patient age (OR for each year of 0.99, CI [0.99-1.00]), and diabetes (OR = 1.38, CI [1.05-1.81]) all increased the risk of post-operative fever. Limitations include the use of fever as a predictor of systemic infection. Approximately 10% of PCNL-treated patients developed fever in the post-operative period despite receiving antibiotic prophylaxis. Risk of post-operative fever increased in the presence of a positive urine bacterial culture, diabetes, staghorn calculi, and a pre-operative nephrostomy.

Thermo-responsive in-situ forming hydrogels as barriers to prevent post-operative peritendinous adhesion.

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Chou, Pang-Yun; Chen, Shih-Heng; Chen, Chih-Hao; Chen, Shih-Hsien; Fong, Yi Teng; Chen, Jyh-Ping

2017-11-01

In this study, we aimed to assess whether thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) could prevent post-operative peritendinous adhesion. The clinical advantages of the thermo-responsive hydrogels are acting as barrier material to block penetration of fibroblasts, providing mobility and flexibility during application and enabling injection through a small opening to fill spaces of any shape after surgery. The thermo-responsiveness of hydrogels was determined to ensure their clinic uses. By grafting hydrophilic biopolymers chitosan (CS) and hyaluronic acid (HA) to PNIPAM, the copolymer hydrogels show enhanced water retention and lubrication, while reduced volume shrinkage during phase transition. In cell culture experiments, the thermo-responsive hydrogel has good biocompatibility and reduces fibroblast penetration. In animal experiments, the effectiveness of preventing post-operative peritendinous adhesion was studied in a rabbit deep flexor tendon model. From gross examination, histology, bending angles of joints, tendon gliding excursion and pull-out force, HA-CS-PNIPAM (HACPN) was confirmed to be the best barrier material to prevent post-operative peritendinous adhesion compared to PNIPAM and CS-PNIPAM (CPN) hydrogels and a commercial barrier film Seprafilm®. There was no significant difference in the breaking strength of HACPN-treated tendons and spontaneously healed ones, indicating HACPN hydrogel application did not interfere with normal tendon healing. We conclude that HACPN hydrogel can provide the best functional outcomes to significantly prevent post-operative tendon adhesion in vivo. We prepared thermo-responsive in-situ forming hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) to prevent post-operative peritendinous adhesion. The injectable barrier hydrogel could have better anti-adhesive properties than current commercial products by acting as barrier material to block penetration of fibroblasts

Complement Activation Induces Neutrophil Adhesion and Neutrophil-Platelet Aggregate Formation on Vascular Endothelial Cells

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Magdalena Riedl

2017-01-01

Discussion: Therefore, our findings of (i neutrophils adhering to complement-activated endothelial cells, (ii the formation of neutrophil-platelet aggregates on endothelial cells, and (iii the ability of aHUS serum to induce similar effects identify a possible role for neutrophils in aHUS manifestation.

Platelet serotonin promotes the recruitment of neutrophils to sites of acute inflammation in mice

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Suidan, Georgette L.; Demers, Melanie; Herr, Nadine; Carbo, Carla; Brill, Alexander; Cifuni, Stephen M.; Mauler, Maximilian; Cicko, Sanja; Bader, Michael; Idzko, Marco; Bode, Christoph

2013-01-01

The majority of peripheral serotonin is stored in platelets, which secrete it on activation. Serotonin releases Weibel-Palade bodies (WPBs) and we asked whether absence of platelet serotonin affects neutrophil recruitment in inflammatory responses. Tryptophan hydroxylase (Tph)1–deficient mice, lacking non-neuronal serotonin, showed mild leukocytosis compared with wild-type (WT), primarily driven by an elevated neutrophil count. Despite this, 50% fewer leukocytes rolled on unstimulated mesenteric venous endothelium of Tph1−/− mice. The velocity of rolling leukocytes was higher in Tph1−/− mice, indicating fewer selectin-mediated interactions with endothelium. Stimulation of endothelium with histamine, a secretagogue of WPBs, or injection of serotonin normalized the rolling in Tph1−/− mice. Diminished rolling in Tph1−/− mice resulted in reduced firm adhesion of leukocytes after lipopolysaccharide treatment. Blocking platelet serotonin uptake with fluoxetine in WT mice reduced serum serotonin by > 80% and similarly reduced leukocyte rolling and adhesion. Four hours after inflammatory stimulation, neutrophil extravasation into lung, peritoneum, and skin wounds was reduced in Tph1−/− mice, whereas in vitro neutrophil chemotaxis was independent of serotonin. Survival of lipopolysaccharide-induced endotoxic shock was improved in Tph1−/− mice. In conclusion, platelet serotonin promotes the recruitment of neutrophils in acute inflammation, supporting an important role for platelet serotonin in innate immunity. PMID:23243271

Cathepsin G-dependent modulation of platelet thrombus formation in vivo by blood neutrophils.

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Nauder Faraday

Full Text Available Neutrophils are consistently associated with arterial thrombotic morbidity in human clinical studies but the causal basis for this association is unclear. We tested the hypothesis that neutrophils modulate platelet activation and thrombus formation in vivo in a cathepsin G-dependent manner. Neutrophils enhanced aggregation of human platelets in vitro in dose-dependent fashion and this effect was diminished by pharmacologic inhibition of cathepsin G activity and knockdown of cathepsin G expression. Tail bleeding time in the mouse was prolonged by a cathepsin G inhibitor and in cathepsin G knockout mice, and formation of neutrophil-platelet conjugates in blood that was shed from transected tails was reduced in the absence of cathepsin G. Bleeding time was highly correlated with blood neutrophil count in wildtype but not cathepsin G deficient mice. In the presence of elevated blood neutrophil counts, the anti-thrombotic effect of cathepsin G inhibition was greater than that of aspirin and additive to it when administered in combination. Both pharmacologic inhibition of cathepsin G and its congenital absence prolonged the time for platelet thrombus to form in ferric chloride-injured mouse mesenteric arterioles. In a vaso-occlusive model of ischemic stroke, inhibition of cathepsin G and its congenital absence improved cerebral blood flow, reduced histologic brain injury, and improved neurobehavioral outcome. These experiments demonstrate that neutrophil cathepsin G is a physiologic modulator of platelet thrombus formation in vivo and has potential as a target for novel anti-thrombotic therapies.

Safety relevant failure mechanisms in the post-operational phase

International Nuclear Information System (INIS)

Mayer, Gerhard; Stiller, Jan Christopher; Roemer, Sarah

2017-03-01

When the 13"t"h amendment of the Atomic Energy Act came into force, eight Germ an nuclear power plant units had their power operating licences revoked and are now in the so-called post operation phase. Of the remaining nuclear power plants, one have by now also entered the post operation phase, with those left in operation bound for entering this phase sometime between now and the end of 2022. Therefore, failure mechanisms that are particularly relevant for post operation were to be identified and described in the frame of the present project. To do so, three major steps were taken: Firstly, recent national and international pertinent literature was evaluated to obtain indications of failure mechanisms in the post operation phase. It turned out that most of the national and international literature deals with the general procedure of the transition from power operation to decommissioning and dismantling. However, there were also some documents providing detailed indications of possible failure mechanisms in post operation. This includes e.g. the release of radioactive materials caused by the drop of containers, chemical impacts on systems important to safety in connection with decontamination work, and corrosion in connection with the storage of the core in the spent fuel pool, with the latter leading to the jamming of the fuel assemblies in the storage racks and a possible reduction of coolant circulation. In a second step, three safety analyses of pressurised water reactors prepared by the respective plant operators were evaluated to identify failure mechanisms based on systems engineering. The failure mechanisms that were found here include e.g. faults in the boric acid concentration of the reactor coolant, damage to the equipment airlock upon the unloading of Castor casks, leakages in connection with primary system decontamination, and the drop of packages holding radioactive residual materials or waste with subsequent mobilisation of radioactive aerosols

Human neutrophils in auto-immunity.

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Thieblemont, Nathalie; Wright, Helen L; Edwards, Steven W; Witko-Sarsat, Véronique

2016-04-01

Human neutrophils have great capacity to cause tissue damage in inflammatory diseases via their inappropriate activation to release reactive oxygen species (ROS), proteases and other tissue-damaging molecules. Furthermore, activated neutrophils can release a wide variety of cytokines and chemokines that can regulate almost every element of the immune system. In addition to these important immuno-regulatory processes, activated neutrophils can also release, expose or generate neoepitopes that have the potential to break immune tolerance and result in the generation of autoantibodies, that characterise a number of human auto-immune diseases. For example, in vasculitis, anti-neutrophil cytoplasmic antibodies (ANCA) that are directed against proteinase 3 or myeloperoxidase are neutrophil-derived autoantigens and activated neutrophils are the main effector cells of vascular damage. In other auto-immune diseases, these neutrophil-derived neoepitopes may arise from a number of processes that include release of granule enzymes and ROS, changes in the properties of components of their plasma membrane as a result of activation or apoptosis, and via the release of Neutrophil Extracellular Traps (NETs). NETs are extracellular structures that contain chromatin that is decorated with granule enzymes (including citrullinated proteins) that can act as neo-epitopes to generate auto-immunity. This review therefore describes the processes that can result in neutrophil-mediated auto-immunity, and the role of neutrophils in the molecular pathologies of auto-immune diseases such as vasculitis, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We discuss the potential role of NETs in these processes and some of the debate in the literature regarding the role of this phenomenon in microbial killing, cell death and auto-immunity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia.

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Tiidus, Peter M; Deller, Mirada; Bombardier, Eric; Gül, Mustafa; Liu, X Linda

2005-01-01

This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO), a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD) and beta-glucuronidase (betaGLU), as markers of muscle damage. Significant elevations of MPO, G6PD and betaGLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and betaGLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

Estrogen supplementation failed to attenuate biochemical indices of neutrophil infiltration or damage in rat skeletal muscles following ischemia

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PETER M TIIDUS

2005-01-01

Full Text Available This study examined the effects of estrogen supplementation on markers of neutrophil infiltration and damage in skeletal muscle of rats following ischemia. Male and female gonad-intact rats, with or without 14 days of estrogen supplementation were subjected to two hours of hind-limb ischemia and sacrificed at 24, 48 or 72 hours post-ischemia. Control animals were sacrificed without ischemia. Plantaris and red and white gastrocneimus muscles were removed and assayed for myeloperoxidase (MPO, a marker of neutrophil infiltration, and glucose-6-phosphate dehydrogenase (G6PD and ß-glucuronidase (GLU, as markers of muscle damage. Significant elevations of MPO, G6PD and GLU activities were observed at various time points post-ischemia. No systematic differences between genders were noted in any of the measures. Estrogen supplementation in both male and female animals failed to significantly attenuate post-ischemia increases in MPO, G6PD and GLU activities in any of the muscles studied and in some cases accentuated activities of some of these measures. Unlike previous findings following exercise in skeletal muscle, this study failed to demonstrate estrogen-induced attenuation of indices of neutrophil infiltration or damage in skeletal muscles of rats up to 72 hours following ischemia. This demonstrates that estrogen may not consistently attenuate neutrophil infiltration and that a number of variables including damage modality, tissue or estrogen level may influence this.

Heterogeneity of neutrophil antibodies in patients with primary Sjögren's syndrome.

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Lamour, A; Le Corre, R; Pennec, Y L; Cartron, J; Youinou, P

1995-11-01

Our aims were to determine the prevalence of neutrophil antibodies in patients with primary Sjögren's syndrome (pSS), identify their target antigen(s), and evaluate their functional significance. Neutrophil antibodies were detected using an indirect immunofluorescence (IIIF) test and an enzyme-linked immunosorbent assay (ELISA), using recombinant human Fc-gamma receptor (Fc gamma RIIIb) as a capture agent. Luminol-dependent chemiluminescence was then measured by an established technique. Antibodies to neutrophils were detected in 30 of 66 patients (45%) and categorized on the basis of positivity for the two assays: IIF+/ELISA+ (group A: five patients), IIF+/ELISA- (group B: five patients), and IFF-/ELISA+ (group C: 20 patients). All positive sera contained antibodies directed to the neutrophil specific Fc gamma RIIIb, and none of them bound to NAnull neutrophils. The titer of neutrophil-reactive antibodies (groups A and B) showed no correlation with the neutrophil count, but these autoantibodies did reduce the cell ability to generate a respiratory burst. Thus, neutrophil antibodies are common in patients with pSS. Their main target appears to be Fc gamma RIII, and this may partly account for the dysfunction in Fc gamma R-mediated clearance by the reticuloendothelial system reported in these patients.

Effectiveness of benzocaine in reducing deep cavity restoration and post-extraction stress in dental patients

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Khalid H. Al-Samadani

2015-11-01

Full Text Available Objectives: To investigate the effectiveness of topical anesthetic, 20% benzocaine in relieving pain and stress in patients following deep cavity restoration and extraction of teeth under local anesthesia (LA. Methods: A prospective clinical trial was conducted from October 2014 until April 2015 at Taibah University, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. Forty-five patients were included in the 20% benzocaine group, and 46 in the normal saline group. Evaluation of the dental stress was made pre-operatively and immediately post-operative treatment using the visual analogue scale (VAS. Furthermore, discomfort of the injections were recorded by the patients after each treatment on standard 100 mm VAS, tagged at the endpoints with “no pain” (0 mm and “unbearable pain” (100 mm. Results: There were statistically significant differences between the mean stress scores for patients in the benzocaine and normal saline groups post-operatively (p=0.002. There were significant differences between the mean pain scores for patients in the post buccal injection (p=0.001, post palatal injection (p=0.01, and the post inferior alveolar nerve block groups (p=0.02. Buccal, palatal, and inferior alveolar nerve block injections were more painful for patients in the normal saline group than the benzocaine group. Conclusion: This investigation has demonstrated that post-operative stress associated with deep cavity restoration and dental extractions under LA can be reduced by the application of topical anesthetic (20% benzocaine at the operative site for intra-oral injections.

Alcohol Consumption Increases Post-Operative Infection but Not Mortality: A Systematic Review and Meta-Analysis.

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Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue

2015-12-01

Alcohol consumption causes multiple comorbidities with potentially negative outcome after operations. The aims are to study the association between alcohol consumption and post-operative non-surgical site infections and mortality and to determine the impact of peri-operative interventions. MEDLINE, Embase, and The Cochrane Library were searched systematically. Observational studies reporting patients with a defined amount of alcohol consumption and randomized controlled trials (RCTs) aimed at reducing outcomes were included. Meta-analyses were performed separately for observational studies and RCTs. Thirteen observational studies and five RCTs were identified. Meta-analyses of observational studies showed more infections in those consuming more than two units of alcohol per day compared with drinking less in both unadjusted and adjusted data. No association between alcohol consumption and mortality was found. Meta-analyses of RCTs showed that interventions reduce infections but not mortality in patients with alcohol abuse. Consumption of more than two units of alcohol per day increases post-operative non-surgical site infections. Alcohol-refraining interventions in patients with high daily alcohol consumption appear to reduce infections. The impact in patients with lesser intake is unknown. Further studies are needed.

Does Injection of Lidocaine with 1/100000 Epinephrine Immediately before Lateral Osteotomy Reduce Post-Operative Periorbital Edema and Ecchymosis in Rhinoplasty?

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mansoor zojajy

2014-06-01

Full Text Available Background: Postoperative periorbital edema and ecchymosis are common after rhinoplasty. We studied the effect of local injection of Lidocaine/Adrenaline immediately before osteotomy on prevention of post-operative periorbital edema and ecchymosis in rhinoplasty.Materials and Methods: Thirty healthy candidates for rhinoplasty were enrolled in the self-controlled clinical trial study. Lidocaine/Adrenaline solution injected randomly to one side just prior to the lateral osteotomy. The opposite side used as a control. The degree of edema/ecchymosis on both sides was compared on the 1st, 2nd and 7th day postoperatively.Results: Mean of severity of edema, 24 hours after operation was 3in both sides, (Mann-whitney U; p=0.829. Mean of severity of edema, 48 hours after operation was 2 in both sides (Mann-whitney U; p=0.867 and it was 1 in both sides 7 days after operation (Mann-whitney U; p=0.756.There was no significant difference between two sides. Mean of severity of ecchymosis, 24 hours after operation was 3 in both sides (Mann-whitney U; p=0.692. Mean of severity of ecchymosis, 48 hours after operation was 2 in both sides (Mann-whitney U; p=0.655 and it was 1 in both sides 7 days after operation (Mann-whitney U; p=0.873. There was no significant difference between two sides.Conclusion: local injection of Lidocaine/Adrenaline solution immediately before lateral osteotomy could not reduce postoperative edema and ecchymosis in rhinoplasty.

Post-operative pain control after tonsillectomy: dexametasone vs tramadol.

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Topal, Kubra; Aktan, Bulent; Sakat, Muhammed Sedat; Kilic, Korhan; Gozeler, Mustafa Sitki

2017-06-01

Tramadol was found to be more effective than dexamethasone in post-operative pain control, with long-lasting relief of pain. This study aimed to compare the effects of pre-operative local injections of tramadol and dexamethasone on post-operative pain, nausea and vomiting in patients who underwent tonsillectomy. Sixty patients between 3-13 years of age who were planned for tonsillectomy were included in the study. Patients were divided into three groups. Group 1 was the control group. Patients in Group 2 received 0.3 mg/kg Dexamethasone and Group 3 received 0.1 mg/kg Tramadol injection to the peritonsillary space just before the operation. Patients were evaluated for nausea, vomiting, and pain. When the control and the dexamethasone groups were compared; there were statistically significant differences in pain scores at post-operative 15 and 30 min, whereas there was no statistically significant difference in pain scores at other hours. When the control and tramadol groups were compared, there was a statistically significant difference in pain scores at all intervals. When tramadol and dexamethasone groups were compared, there was no statistically significant difference in pain scores at post-operative 15 and 30 min, 1 and 2 h, whereas there was a statistically significant difference in pain scores at post-operative 6 and 24 h.

Role of β1 Integrin in Tissue Homing of Neutrophils During Sepsis

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Sarangi, Pranita P.; Hyun, Young-Min; Lerman, Yelena V.; Pietropaoli, Anthony P.; Kim, Minsoo

2012-01-01

Aberrant activation of neutrophils during sepsis results in the widespread release of pro-inflammatory mediators, leading to multi-organ system failure and death. However, aberrant activation of neutrophils during sepsis results in the widespread release of harmful inflammatory mediators causing host tissue injuries that can lead to multi organ system failure and death. One of the pivotal components of neutrophil migration during inflammation is the expression of surface integrins. In this study, we show that administration of a cyclic analog of RGD peptide (Arg-Gly-Asp) significantly reduced the number of tissue-invading neutrophils and the degree of sepsis-induced lethality in mice as compared to control peptide. Secondly, β1 integrin (CD29) was highly up-regulated on the neutrophils isolated from both septic patients and animals. Finally, conditional genetic ablation of β1 integrin from granulocytes also improved survival and bacterial clearance in septic animals Thus, our results indicate that expression of β1 integrin is important for modulating neutrophil trafficking during sepsis, and that therapeutics designed against β1 integrins may be beneficial. PMID:22683734

Doxycycline induced photodamage to human neutrophils and tryptophan

International Nuclear Information System (INIS)

Sandberg, S.; Glette, J.; Hopen, G.; Solberg, C.O.

1984-01-01

Neutrophil function were studied following irradiation (340-380 nm) of the cells in the presence of 22 μM doxycycline. At increasing light fluence the locomotion, chemiluminescence and glucose oxidation (by the hexose monophosphate shunt) of the neutrophils steadily decreased. The photodamage increased with increasing preincubation temperature and time and was enhanced in D 2 O, reduced in azide and abolished in anaerobiosis. Superoxide dismutase, catalase or mannitol did not influence the photodamage. Photooxidation of tryptophan in the presence of doxycycline was increased 9-10-fold in D 2 O and nearly abolished in the presence of 0.25 mM NaN 3 , indicating that singlet oxygen is the most important reactive oxygen species in the doxycycline-induced photodamage. The results may explain some of the features of tetracycline-induced photosensitivity and why other authors have obtained diverging results when studying the influence of tetracyclines on neutrophil functions. (author)

Post-operative pain following coblation or monopolar electrocautery tonsillectomy in children: a prospective, single-blinded, randomised comparison.

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Parker, N P; Walner, D L

2011-10-01

To compare post-operative pain following tonsillectomy by either coblation or monopolar electrocautery in children. A parallel-designed, prospective, single-blinded, randomised trial. Ambulatory surgical facility. Eighty otherwise healthy paediatric patients undergoing coblation or electrocautery tonsillectomy by a fellowship-trained paediatric otolaryngologist. (i) The number of post-operative days with severe pain based on subjective qualification by the caretaker, (ii) post-operative days with pain rated ≥ 5 on a scale of 1-10, (iii) post-operative days requiring oral paracetamol/acetaminophen with codeine solution and (iv) post-operative days until resumption of a regular diet were assessed and recorded daily using a post-operative pain survey as a form of daily diary that was returned at the 2-week follow-up visit. Patients were consecutively enrolled into two groups of 40 patients. Average ages were 5.2 years for coblation tonsillectomy and 6.0 years for electrocautery tonsillectomy. The average number of post-operative days with severe pain was 4.2 for coblation and 5.9 for electrocautery (P = 0.006), days rating pain ≥ 5 were 3.6 for coblation and 4.8 for electrocautery (P = 0.037), days of codeine use were 2.5 for coblation and 2.9 for electrocautery (P = 0.324), and days until resumption of a regular diet were 5.2 for coblation and 6.2 for electrocautery (0.329). Coblation tonsillectomy may reduce post-operative pain and the time until resumption of a regular diet compared to electrocautery tonsillectomy. © 2011 Blackwell Publishing Ltd.

Obesity is associated with more activated neutrophils in African American male youth.

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Xu, X; Su, S; Wang, X; Barnes, V; De Miguel, C; Ownby, D; Pollock, J; Snieder, H; Chen, W; Wang, X

2015-01-01

There is emerging evidence suggesting the role of peripheral blood leukocytes in the pathogenesis of obesity and related diseases. However, few studies have taken a genome-wide approach to investigating gene expression profiles in peripheral leukocytes between obese and lean individuals with the consideration of obesity-related shifts in leukocyte types. We conducted this study in 95 African Americans (AAs) of both genders (age 14-20 years, 46 lean and 49 obese). Complete blood count with differential test (CBC) was performed in whole blood. Genome-wide gene expression analysis was obtained using the Illumina HumanHT-12 V4 Beadchip with RNA extracted from peripheral leukocytes. Out of the 95 participants, 64 had neutrophils stored. The validation study was based on real-time PCR with RNA extracted from purified neutrophils. CBC test suggested that, in males, obesity was associated with increased neutrophil percentage (P=0.03). Genome-wide gene expression analysis showed that, in males, the majority of the most differentially expressed genes were related to neutrophil activation. Validation of the gene expression levels of ELANE (neutrophil elastase) and MPO (myeloperoxidase) in purified neutrophils demonstrated that the expression of these two genes--important biomarkers of neutrophils activation--were significantly elevated in obese males (P=0.01 and P=0.02, respectively). The identification of increased neutrophil percentage and activation in obese AA males suggests that neutrophils have an essential role in the pathogenesis of obesity-related disease. Further functional and mechanistic studies on neutrophils may contribute to the development of novel intervention strategies reducing the burden associated with obesity-related health problems.

Optimal ex vivo expansion of neutrophils from PBSC CD34+ cells by a combination of SCF, Flt3-L and G-CSF and its inhibition by further addition of TPO

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Turner Marc L

2007-10-01

by number, morphology and function (respiratory burst activity. Conclusion Given that platelet transfusion support is available for autologous PBSC transplantation but granulocyte transfusion is generally lacking, and that multilineage expanded PBSC do not reduce thrombocytopenia, we suggest that instead of multilineage expansion selective neutrophil expansion based on this relatively simple cytokine combination might be prioritized for development for clinical use as an adjunct to unmanipulated PBSC transplantation to reduce or abrogate post-transplant neutropenia.

Post-operative urinary retention in a general surgical population

DEFF Research Database (Denmark)

Dreijer, Bjørn; Møller, Morten H; Bartholdy, Jens

2011-01-01

Post-operative urine retention is a frequent and serious complication. The aims of this study were to evaluate the prevalence of post-operative urinary retention in a general surgical population and to identify the perioperative risk factors for developing this condition....

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

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Kamoshida, Go; Kikuchi-Ueda, Takane; Nishida, Satoshi; Tansho-Nagakawa, Shigeru; Ubagai, Tsuneyuki; Ono, Yasuo

2018-01-01

Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs), has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA), and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections. PMID:29467765

Pathogenic Bacterium Acinetobacter baumannii Inhibits the Formation of Neutrophil Extracellular Traps by Suppressing Neutrophil Adhesion

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Go Kamoshida

2018-02-01

Full Text Available Hospital-acquired infections caused by Acinetobacter baumannii have become problematic because of high rates of drug resistance. A. baumannii is usually harmless, but it may cause infectious diseases in an immunocompromised host. Although neutrophils are the key players of the initial immune response against bacterial infection, their interactions with A. baumannii remain largely unknown. A new biological defense mechanism, termed neutrophil extracellular traps (NETs, has been attracting attention. NETs play a critical role in bacterial killing by bacterial trapping and inactivation. Many pathogenic bacteria have been reported to induce NET formation, while an inhibitory effect on NET formation is rarely reported. In the present study, to assess the inhibition of NET formation by A. baumannii, bacteria and human neutrophils were cocultured in the presence of phorbol 12-myristate 13-acetate (PMA, and NET formation was evaluated. NETs were rarely observed during the coculture despite neutrophil PMA stimulation. Furthermore, A. baumannii prolonged the lifespan of neutrophils by inhibiting NET formation. The inhibition of NET formation by other bacteria was also investigated. The inhibitory effect was only apparent with live A. baumannii cells. Finally, to elucidate the mechanism of this inhibition, neutrophil adhesion was examined. A. baumannii suppressed the adhesion ability of neutrophils, thereby inhibiting PMA-induced NET formation. This suppression of cell adhesion was partly due to suppression of the surface expression of CD11a in neutrophils. The current study constitutes the first report on the inhibition of NET formation by a pathogenic bacterium, A. baumannii, and prolonging the neutrophil lifespan. This novel pathogenicity to inhibit NET formation, thereby escaping host immune responses might contribute to a development of new treatment strategies for A. baumannii infections.

Post Operative Cognitive Dysfunction (POCD in Geriatric Population

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Rajesh MC

2015-10-01

Full Text Available Post-operative mental dysfunction and confusion in aged patients is a well recognized entity. Commonly known as post-operative delirium and cognitive dysfunction (POCD, these are important for any peri-operative physician dealing with geriatric population. The incidence is more in older patients with pre-existing impairment. Impact of POCD is grave. This can result in poor rehabilitation outcome and increased hospital stay. Incidence ranges from 15-50% with ˂5% for cataract surgery and as high as 60% after hip replacement procedures.

The routine use of post-operative drains in thyroid surgery: an outdated concept.

LENUS (Irish Health Repository)

Prichard, R S

2010-01-01

The use of surgical drains in patients undergoing thyroid surgery is standard surgical teaching. Life-threatening complications, arising from post-operative haematomas, mandates their utilization. There is increasing evidence to suggest that this is an outdated practice. This paper determines whether thyroid surgery can be safely performed without the routine use of drains. A retrospective review of patients undergoing thyroid surgery, over a three year period was performed and post-operative complications documented. One hundred and four thyroidectomies were performed. 63 (60.6%) patients had a partial thyroidectomy, 27 (25.9%) had a total thyroidectomy and 14 (13.5%) had a sub-total thyroidectomy. Suction drains were not inserted in any patient. A cervical haematoma did not develop in any patient in this series and no patient required re-operation. There is no evidence to suggest the routine use of surgical drains following uncomplicated thyroid surgery reduces the rate of haematoma formation or re-operation rates and indeed is now unwarranted.

Neutrophil Extracellular Traps in Ulcerative Colitis

DEFF Research Database (Denmark)

Bjerg Bennike, Tue; Carlsen, Thomas Gelsing; Ellingsen, Torkell

2015-01-01

microscopy and confocal microscopy. RESULTS: We identified and quantified 5711 different proteins with proteomics. The abundance of the proteins calprotectin and lactotransferrin in the tissue correlated with the degree of tissue inflammation as determined by histology. However, fecal calprotectin did...... not correlate. Forty-six proteins were measured with a statistically significant differences in abundances between the UC colon tissue and controls. Eleven of the proteins with increased abundances in the UC biopsies were associated with neutrophils and neutrophil extracellular traps. The findings were...... validated by microscopy, where an increased abundance of neutrophils and the presence of neutrophil extracellular traps by extracellular DNA present in the UC colon tissue were confirmed. CONCLUSIONS: Neutrophils, induced neutrophil extracellular traps, and several proteins that play a part in innate...

IFN-γ protects from lethal IL-17 mediated viral encephalomyelitis independent of neutrophils

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Savarin Carine

2012-05-01

Full Text Available Abstract Background The interplay between IFN-γ, IL-17 and neutrophils during CNS inflammatory disease is complex due to cross-regulatory factors affecting both positive and negative feedback loops. These interactions have hindered the ability to distinguish the relative contributions of neutrophils, Th1 and Th17 cell-derived effector molecules from secondary mediators to tissue damage and morbidity. Methods Encephalitis induced by a gliatropic murine coronavirus was used as a model to assess the direct contributions of neutrophils, IFN-γ and IL-17 to virus-induced mortality. CNS inflammatory conditions were selectively manipulated by adoptive transfer of virus-primed wild-type (WT or IFN-γ deficient (GKO memory CD4+ T cells into infected SCID mice, coupled with antibody-mediated neutrophil depletion and cytokine blockade. Results Transfer of GKO memory CD4+ T cells into infected SCID mice induced rapid mortality compared to recipients of WT memory CD4+ T cells, despite similar virus control and demyelination. In contrast to recipients of WT CD4+ T cells, extensive neutrophil infiltration and IL-17 expression within the CNS in recipients of GKO CD4+ T cells provided a model to directly assess their contribution(s to disease. Recipients of WT CD4+ T cells depleted of IFN-γ did not express IL-17 and were spared from mortality despite abundant CNS neutrophil infiltration, indicating that mortality was not mediated by excessive CNS neutrophil accumulation. By contrast, IL-17 depletion rescued recipients of GKO CD4+ T cells from rapid mortality without diminishing neutrophils or reducing GM-CSF, associated with pathogenic Th17 cells in CNS autoimmune models. Furthermore, co-transfer of WT and GKO CD4+ T cells prolonged survival in an IFN-γ dependent manner, although IL-17 transcription was not reduced. Conclusions These data demonstrate that IL-17 mediates detrimental clinical consequences in an IFN-γ-deprived environment, independent of

Neutrophils: potential therapeutic targets in tularemia?

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Lee-Ann H Allen

2013-12-01

Full Text Available The central role of neutrophils in innate immunity and host defense has long been recognized, and the ability of these cells to efficiently engulf and kill invading bacteria has been extensively studied, as has the role of neutrophil apoptosis in resolution of the inflammatory response. In the past few years additional immunoregulatory properties of neutrophils were discovered, and it is now clear that these cells play a much greater role in control of the immune response than was previously appreciated. In this regard, it is noteworthy that Francisella tularensis is one of relatively few pathogens that can successfully parasitize neutrophils as well as macrophages, DC and epithelial cells. Herein we will review the mechanisms used by F. tularensis to evade elimination by neutrophils. We will also reprise effects of this pathogen on neutrophil migration and lifespan as compared with other infectious and inflammatory disease states. In addition, we will discuss the evidence which suggests that neutrophils contribute to disease progression rather than effective defense during tularemia, and consider whether manipulation of neutrophil migration or turnover may be suitable adjunctive therapeutic strategies.

Biochemical changes in neutrophils of cervical cancer patients treated with 60Co

International Nuclear Information System (INIS)

Krishnamurthy, Vijayalakshmi; Gunalan, Gayathri; Haridas, Sumathy; Thangamani, Vanitha

2008-01-01

Cervical carcinoma is the second most common malignancy of the female genital tract in India. The highest incidence occurs at Chennai. This study was conducted on 30 women with biopsy-proved squamous cell carcinoma of the cervix of stage IIb. The neutrophil count increased significantly in cancer patients compared to control subjects. Total protein, glycogen and total lipid increased in neutrophils of cervical cancer patients. The level of cholestrol, triglycerides and fatty acids increased significantly in neutrophils of such patients compared to control subjects. The activity of alkaline phosphatase increased significantly in cervical cancer patients. Upon treatment with cobalt-60, these changes were brought to near-normal levels. This study highlights the impairment in the neutrophil function in cervical cancer patients, which may lead to reduced immune status. (author)

Disentangling the effects of tocilizumab on neutrophil survival and function.

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Gaber, Timo; Hahne, Martin; Strehl, Cindy; Hoff, Paula; Dörffel, Yvonne; Feist, Eugen; Burmester, Gerd-Rüdiger; Buttgereit, Frank

2016-06-01

The synovial tissue in rheumatoid arthritis (RA) represents a hypoxic environment with up-regulated pro-inflammatory cytokines and cellular infiltrates including neutrophils. Although inhibition of the interleukin (IL)6 receptor pathway by tocilizumab is a potent treatment option for RA, it may also cause adverse effects such as an occasionally high-grade neutropenia. We analysed the impact of tocilizumab on survival, mediator secretion, oxidative burst, phagocytosis and energy availability of high-dose toll-like receptor (TLR)2/4-stimulated neutrophils (to mimic an arthritis flare) under normoxic versus hypoxic conditions. Human neutrophils were purified, pre-treated with varying doses of tocilizumab, dexamethasone or human IgG1 and high-dose-stimulated with lipopolysaccharide (LPS) alone-triggering TLR2/4-, LPS plus IL6, or left unstimulated. Cells were then incubated under normoxic (18 % O2) or hypoxic (1 % O2) conditions and subsequently analysed. Neutrophil survival and energy availability were significantly decreased by tocilizumab in a dose-dependent manner in high-dose TLR2/4-stimulated cells, but to a greater extent under normoxia as compared to hypoxia. We also found high-dose LPS-stimulated oxidative burst and phagocytosis of neutrophils to be higher under hypoxic versus normoxic conditions, but this difference was reduced by tocilizumab. Finally, we observed that tocilizumab affected neutrophil mediator secretion as a function of oxygen availability. Tocilizumab is known for both beneficial effects and a higher incidence of neutropenia when treating RA patients. Our results suggest that both effects can at least in part be explained by a reduction in neutrophil survival, a dose-dependent inhibition of hypoxia-induced NADPH oxidase-mediated oxidative burst and phagocytosis of infiltrating hypoxic neutrophils and an alteration of mediator secretion.

Sepsis Induces a Dysregulated Neutrophil Phenotype That Is Associated with Increased Mortality

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Jaimin M. Patel

2018-01-01

Full Text Available Background. Neutrophil dysfunction in sepsis has been implicated in the pathogenesis of multiorgan failure; however, the role of neutrophil extracellular traps (NETs remains uncertain. We aimed to determine the sequential changes in ex vivo NETosis and its relationship with mortality in patients with sepsis and severe sepsis. Methods. This was a prospective observational cohort study enrolling 21 healthy age-matched controls and 39 sepsis and 60 severe sepsis patients from acute admissions to two UK hospitals. Patients had sequential bloods for the ex vivo assessment of NETosis in response to phorbol-myristate acetate (PMA using a fluorometric technique and chemotaxis using time-lapse video microscopy. Continuous data was tested for normality, with appropriate parametric and nonparametric tests, whilst categorical data was analysed using a chi-squared test. Correlations were performed using Spearman’s rho. Results. Ex vivo NETosis was reduced in patients with severe sepsis, compared to patients with sepsis and controls (p=0.002. PMA NETosis from patients with septic shock was reduced further (p<0.001 compared to controls. The degree of metabolic acidosis correlated with reduced NETosis (p<0.001, and this was replicated when neutrophils from healthy donors were incubated in acidotic media. Reduced NETosis at baseline was associated with an increased 30-day (p=0.002 and 90-day mortality (p=0.014 in sepsis patients. These findings were accompanied by defects in neutrophil migration and delayed apoptosis. Resolution of sepsis was not associated with the return to baseline levels of NETosis or migration. Conclusions. Sepsis induces significant changes in neutrophil function with the degree of dysfunction corresponding to the severity of the septic insult which persists beyond physiological recovery from sepsis. The changes induced lead to the failure to effectively contain and eliminate the invading pathogens and contribute to sepsis

Influence of a Shorter Duration of Post-Operative Antibiotic Prophylaxis on Infectious Complications in Patients Undergoing Elective Liver Resection.

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Sakoda, Masahiko; Iino, Satoshi; Mataki, Yuko; Kawasaki, Yota; Kurahara, Hiroshi; Maemura, Kosei; Ueno, Shinichi; Natsugoe, Shoji

Antibiotic prophylaxis has been recommended to reduce post-operative infectious complications. Discontinuation of post-operative antibiotic administration within 24 hours of operation is currently recommended. Many surgeons, however, conventionally tend to extend the duration of prophylactic antibiotic use. In this study, we performed a retrospective analysis to assess the efficacy of extended post-operative antibiotic use in patients who underwent elective liver resection. A total of 208 consecutive patients who underwent liver resection without biliary reconstruction were investigated. Patients were divided into two groups according to the duration of post-operative antibiotic use: Only once after the operation (the post-operative day [POD] 0 group) and until three days after the operation (the POD 3 group). Post-operative complications in the two groups were analyzed and compared. Incisional surgical site infections (SSIs) were observed in 5% of the POD 0 group and 3% of the POD 3 group (p = 0.517). Organ/space SSIs were observed in 2% of the POD 0 group and 3% of the POD 3 group (p = 0.694). Overall infectious complications including SSIs and remote site infections were observed in 12% of the POD 0 group and 11% of the POD 3 group. Multi-variable analyses revealed that the short-term post-operative antibiotic regimen did not confer additional risk for infectious complications. In elective liver resection, the administration of prophylactic antibiotics on the operative day alone appears to be sufficient, because no additional benefit in the incidence of post-operative infectious complications was conferred on patients given antibiotic agents for three days.

Effect of sevoflurane on human neutrophil apoptosis.

LENUS (Irish Health Repository)

Tyther, R

2012-02-03

BACKGROUND AND OBJECTIVE: Both chronic occupational exposure to volatile anaesthetic agents and acute in vitro exposure of neutrophils to isoflurane have been shown to inhibit the rate of apoptosis of human neutrophils. It is possible that inhibition of neutrophil apoptosis arises through delaying mitochondrial membrane potential collapse. We assessed mitochondrial depolarization and apoptosis in unexposed neutrophils and neutrophils exposed to sevoflurane in vivo. METHODS: A total of 20 mL venous blood was withdrawn pre- and postinduction of anaesthesia, the neutrophils isolated and maintained in culture. At 1, 12 and 24 h in culture, the percentage of neutrophil apoptosis was assessed by dual staining with annexin V-FITC and propidium iodide. Mitochondrial depolarization was measured using the dual emission styryl dye JC-1. RESULTS: Apoptosis was significantly inhibited in neutrophils exposed to sevoflurane in vivo at 24 (exposed: 38 (12)% versus control: 28 (11)%, P = 0.001), but not at 1 or 12 h, in culture. Mitochondrial depolarization was not delayed in neutrophils exposed to sevoflurane. CONCLUSIONS: The most important findings are that sevoflurane inhibits neutrophil apoptosis in vivo and that inhibition is not mediated primarily by an effect on mitochondrial depolarization.

Neutrophil programming dynamics and its disease relevance.

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Ran, Taojing; Geng, Shuo; Li, Liwu

2017-11-01

Neutrophils are traditionally considered as first responders to infection and provide antimicrobial host defense. However, recent advances indicate that neutrophils are also critically involved in the modulation of host immune environments by dynamically adopting distinct functional states. Functionally diverse neutrophil subsets are increasingly recognized as critical components mediating host pathophysiology. Despite its emerging significance, molecular mechanisms as well as functional relevance of dynamically programmed neutrophils remain to be better defined. The increasing complexity of neutrophil functions may require integrative studies that address programming dynamics of neutrophils and their pathophysiological relevance. This review aims to provide an update on the emerging topics of neutrophil programming dynamics as well as their functional relevance in diseases.

Decreased activity of neutrophils in the presence of diferuloylmethane (curcumin) involves protein kinase C inhibition.

Science.gov (United States)

Jancinová, Viera; Perecko, Tomás; Nosál, Radomír; Kostálová, Daniela; Bauerová, Katarína; Drábiková, Katarína

2009-06-10

Diferuloylmethane (curcumin) has been shown to act beneficially in arthritis, particularly through downregulated expression of proinflammatory cytokines and collagenase as well as through the modulated activities of T lymphocytes and macrophages. In this study its impact on activated neutrophils was investigated both in vitro and in experimental arthritis. Formation of reactive oxygen species in neutrophils was recorded on the basis of luminol- or isoluminol-enhanced chemiluminescence. Phosphorylation of neutrophil protein kinases C alpha and beta II was assessed by Western blotting, using phosphospecific antibodies. Adjuvant arthritis was induced in Lewis rats by heat-killed Mycobacterium butyricum. Diferuloylmethane or methotrexate was administered over a period of 28 days after arthritis induction. Under in vitro conditions, diferuloylmethane (1-100 microM) reduced dose-dependently oxidant formation both at extra- and intracellular level and it effectively reduced protein kinase C activation. Adjuvant arthritis was accompanied by an increased number of neutrophils in blood and by a more pronounced spontaneous as well as PMA (phorbol myristate acetate) stimulated chemiluminescence. Whereas the arthritis-related alterations in neutrophil count and in spontaneous chemiluminescence were not modified by diferuloylmethane, the increased reactivity of neutrophils to PMA was less evident in diferuloylmethane-treated animals. The effects of diferuloylmethane were comparable with those of methotrexate. Diferuloylmethane was found to be a potent inhibitor of neutrophil functions both in vitro and in experimental arthritis. As neutrophils are considered to be cells with the greatest capacity to inflict damage within diseased joints, the observed effects could represent a further mechanism involved in the antirheumatic activity of diferuloylmethane.

Dry period management and optimization of post-partum reproductive management in dairy cattle.

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Gumen, A; Keskin, A; Yilmazbas-Mecitoglu, G; Karakaya, E; Wiltbank, Mc

2011-09-01

Dry period and early post-partum management are decisive factors for fertility in lactating dairy cows. Previous studies have shown that decreased dry matter intake (DMI) and increased non-esterified fatty acids (NEFA) negatively affect fertility and subsequent milk production. The traditional dry period decreases DMI prior to parturition, resulting in a decrease in energy intake. A negative energy balance increases NEFA concentration, and increased NEFA may impair the immune system, especially by decreasing neutrophil function prior to parturition. Earlier studies have shown that post-partum health disorders, including retained placenta and metritis, were correlated with periparturient neutrophil function. In addition, decreased DMI is also linked to a reduced body condition score (BCS) in dairy cows. These events in the periparturient period negatively affect fertility. Some manipulation, such as shortening the dry period, may be a solution to increased DMI in the periparturient period, preventing post-partum disorders and subsequent fertility issues. This article aims to explain the effects of shortening the dry period on reproduction and early post-partum treatments to improve fertility. In addition, timed artificial insemination protocols will be discussed for use during the post-partum period to improve fertility in dairy cows. © 2011 Blackwell Verlag GmbH.

Urinary tract infections and post-operative fever in percutaneous nephrolithotomy

NARCIS (Netherlands)

Gutierrez, Jorge; Smith, Arthur; Geavlete, Petrisor; Shah, Hemendra; Kural, Ali Riza; de Sio, Marco; Amón Sesmero, José H.; Hoznek, András; de la Rosette, Jean

2013-01-01

To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre-operative urine samples and who

Dynamic interactions of neutrophils and biofilms

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Josefine Hirschfeld

2014-12-01

Full Text Available Background: The majority of microbial infections in humans are biofilm-associated and difficult to treat, as biofilms are highly resistant to antimicrobial agents and protect themselves from external threats in various ways. Biofilms are tenaciously attached to surfaces and impede the ability of host defense molecules and cells to penetrate them. On the other hand, some biofilms are beneficial for the host and contain protective microorganisms. Microbes in biofilms express pathogen-associated molecular patterns and epitopes that can be recognized by innate immune cells and opsonins, leading to activation of neutrophils and other leukocytes. Neutrophils are part of the first line of defense and have multiple antimicrobial strategies allowing them to attack pathogenic biofilms. Objective/design: In this paper, interaction modes of neutrophils with biofilms are reviewed. Antimicrobial strategies of neutrophils and the counteractions of the biofilm communities, with special attention to oral biofilms, are presented. Moreover, possible adverse effects of neutrophil activity and their biofilm-promoting side effects are discussed. Results/conclusion: Biofilms are partially, but not entirely, protected against neutrophil assault, which include the processes of phagocytosis, degranulation, and formation of neutrophil extracellular traps. However, virulence factors of microorganisms, microbial composition, and properties of the extracellular matrix determine whether a biofilm and subsequent microbial spread can be controlled by neutrophils and other host defense factors. Besides, neutrophils may inadvertently contribute to the physical and ecological stability of biofilms by promoting selection of more resistant strains. Moreover, neutrophil enzymes can degrade collagen and other proteins and, as a result, cause harm to the host tissues. These parameters could be crucial factors in the onset of periodontal inflammation and the subsequent tissue breakdown.

Biomaterial associated impairment of local neutrophil function.

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Kaplan, S S; Basford, R E; Kormos, R L; Hardesty, R L; Simmons, R L; Mora, E M; Cardona, M; Griffith, B L

1990-01-01

The effect of biomaterials on neutrophil function was studied in vitro to determine if these materials activated neutrophils and to determine the subsequent response of these neutrophils to further stimulation. Two biomaterials--polyurethane, a commonly used substance, and Velcro pile (used in the Jarvik 7 heart)--were evaluated. Two control substances, polyethylene and serum-coated polystyrene, were used for comparison. Neutrophil superoxide release was measured following incubation with these materials for 10, 30, and 120 min in the absence of additional stimulation and after stimulation with formylmethionylleucylphenylalanine (fMLP) or phorbol myristate acetate (PMA). The authors observed that the incubation of neutrophils on both polyurethane and Velcro resulted in substantially increased superoxide release that was greater after the 10 min than after the 30 or 120 min association. These activated neutrophils exhibited a poor additional response to fMLP but responded well to PMA. The effect of implantation of the Novacor left ventricular assist device on peripheral blood neutrophil function was also evaluated. The peripheral blood neutrophils exhibited normal superoxide release and chemotaxis. These studies suggest that biomaterials may have a profound local effect on neutrophils, which may predispose the patient to periprosthetic infection, but that the reactivity of circulating neutrophils is unimpaired.

Neutrophils Compromise Retinal Pigment Epithelial Barrier Integrity

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Jiehao Zhou

2010-01-01

Full Text Available We hypothesized that neutrophils and their secreted factors mediate breakdown of the integrity of the outer blood-retina-barrier by degrading the apical tight junctions of the retinal pigment epithelium (RPE. The effect of activated neutrophils or neutrophil cell lysate on apparent permeability of bovine RPE-Choroid explants was evaluated by measuring [H] mannitol flux in a modified Ussing chamber. The expression of matrix metalloproteinase- (MMP- 9 in murine peritoneal neutrophils, and the effects of neutrophils on RPE tight-junction protein expression were assessed by confocal microscopy and western blot. Our results revealed that basolateral incubation of explants with neutrophils decreased occludin and ZO-1 expression at 1 and 3 hours and increased the permeability of bovine RPE-Choroid explants by >3-fold (P<.05. Similarly, basolateral incubation of explants with neutrophil lysate decreased ZO-1 expression at 1 and 3 hours (P<.05 and increased permeability of explants by 75%. Further, we found that neutrophils prominently express MMP-9 and that incubation of explants with neutrophils in the presence of anti-MMP-9 antibody inhibited the increase in permeability. These data suggest that neutrophil-derived MMP-9 may play an important role in disrupting the integrity of the outer blood-retina barrier.

Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study

Science.gov (United States)

Muñoz, Manuel; Gómez-Ramírez, Susana; Martín-Montañez, Elisa; Naveira, Enrique; Seara, Javier; Pavía, José

2014-01-01

Background Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20–50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective. Materials and methods Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis. Results Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2–2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (−25.5 to 62.1 €/patient for iron sucrose, and −51.1 to 64.4 €/patient for ferric carboxymaltose). Discussion In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method. PMID:24120595

Post-operative sleep disturbance: causes, factors and effects on outcome

DEFF Research Database (Denmark)

Rosenberg, J; Rosenberg-Adamsen, S; Kehlet, H

1995-01-01

Post-operative sleep disturbance, with suppression of rapid eye movement sleep and slow wave sleep followed by a subsequent rebound, seems to be related to the magnitude of trauma and thereby to the surgical stress response. In this context, cortisol, autonomic stimulation, and certain cytokines...... may lead to abnormal sleep. Furthermore, the environment, pain and the administration of analgesics seem to be important factors in the precipitation of sleep abnormalities. Post-operative sleep disturbance may contribute to the development of episodic hypoxaemia, haemodynamic instability and altered...... mental status, all of which have an influence on post-operative morbidity and mortality. Prevention or reduction of the post-operative sleep disturbance may be achieved by minimizing surgical trauma, changing the conventional nursing procedures, avoiding opioids and treating pain with non...

Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

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Endalew Yizengaw

2016-11-01

Full Text Available Immunologically, active visceral leishmaniasis (VL is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood.In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites.Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL.

Cytoplasmic lipid bodies of human neutrophilic leukocytes

International Nuclear Information System (INIS)

Weller, P.F.; Ackerman, S.J.; Nicholson-Weller, A.; Dvorak, A.M.

1989-01-01

The morphology and function of cytoplasmic lipid bodies in human neutrophils were evaluated. By transmission electron microscopy, neutrophil lipid bodies were cytoplasmic inclusions, usually several microns in diameter, that occasionally coalesced to attain a diameter up to 7 microM. Neutrophil lipid bodies were not enveloped by membrane but were often surrounded by a more electron-dense shell at their periphery. Normal peripheral blood neutrophils contained an average of approximately one lipid body per cell. Lipid bodies appeared in greater numbers in neutrophils from inflammatory lesions. Perturbation of neutrophils during conventional methods of cell isolation and purification modestly increased lipid body numbers in neutrophils, whereas incubation of neutrophils with 1 microM oleic acid rapidly induced lipid body formation over 30 to 60 minutes. After granulocytes were incubated for 2 hours with 3H-fatty acids, including arachidonic, oleic, and palmitic acids, electron microscopic autoradiography demonstrated that lipid bodies represented the predominant intracellular sites of localization of each of the three 3H-fatty acids. There was lesser labeling noted in the perinuclear cisterna, but not in cell membranes. Virtually all of each of the three 3H-fatty acids incorporated by the neutrophils were esterified into chromatographically resolved classes of neutral lipids or phospholipids. These findings indicate that cytoplasmic lipid bodies are more prominent in neutrophils in vivo engaged in inflammatory responses and that these organelles in human neutrophils function as sites of deposition of esterified, incorporated fatty acids

fMLP-Induced IL-8 Release Is Dependent on NADPH Oxidase in Human Neutrophils

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María A. Hidalgo

2015-01-01

Full Text Available N-Formyl-methionyl-leucyl-phenylalanine (fMLP and platelet-activating factor (PAF induce similar intracellular signalling profiles; but only fMLP induces interleukin-8 (IL-8 release and nicotinamide adenine dinucleotide phosphate reduced (NADPH oxidase activity in neutrophils. Because the role of ROS on IL-8 release in neutrophils is until now controversial, we assessed if NADPH oxidase is involved in the IL-8 secretions and PI3K/Akt, MAPK, and NF-κB pathways activity induced by fMLP. Neutrophils were obtained from healthy volunteers. IL-8 was measured by ELISA, IL-8 mRNA by qPCR, and ROS production by luminol-amplified chemiluminescence, reduction of ferricytochrome c, and FACS. Intracellular pH changes were detected by spectrofluorescence. ERK1/2, p38 MAPK, and Akt phosphorylation were analysed by immunoblotting and NF-κB was analysed by immunocytochemistry. Hydroxy-3-methoxyaceto-phenone (HMAP, diphenyleneiodonium (DPI, and siRNA Nox2 reduced the ROS and IL-8 release in neutrophils treated with fMLP. HMAP, DPI, and amiloride (a Na+/H+ exchanger inhibitor inhibited the Akt phosphorylation and did not affect the p38 MAPK and ERK1/2 activity. DPI and HMAP reduced NF-κB translocation induced by fMLP. We showed that IL-8 release induced by fMLP is dependent on NADPH oxidase, and ROS could play a redundant role in cell signalling, ultimately activating the PI3K/Akt and NF-κB pathways in neutrophils.

Tamoxifen induces apoptotic neutrophil efferocytosis in horses.

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Olave, C; Morales, N; Uberti, B; Henriquez, C; Sarmiento, J; Ortloff, A; Folch, H; Moran, G

2018-03-01

Macrophages and neutrophils are important cellular components in the process of acute inflammation and its subsequent resolution, and evidence increasingly suggests that they play important functions during the resolution of chronic, adaptive inflammatory processes. Exacerbated neutrophil activity can be harmful to surrounding tissues; this is important in a range of diseases, including allergic asthma and chronic obstructive pulmonary disease in humans, and equine asthma (also known as recurrent airway obstruction (RAO). Tamoxifen (TX) is a non-steroidal estrogen receptor modulator with effects on cell growth and survival. Previous studies showed that TX treatment in horses with induced acute pulmonary inflammation promoted early apoptosis of blood and BALF neutrophils, reduction of BALF neutrophils, and improvement in animals' clinical status. The aim of this study was to describe if TX induces in vitro efferocytosis of neutrophils by alveolar macrophages. Efferocytosis assay, myeloperoxidase (MPO) detection and translocation phosphatidylserine (PS) were performed on neutrophils isolated from peripheral blood samples from five healthy horses. In in vitro samples from heathy horses, TX treatment increases the phenomenon of efferocytosis of peripheral neutrophils by alveolar macrophages. Similar increases in supernatant MPO concentration and PS translocation were observed in TX-treated neutrophils, compared to control cells. In conclusion, these results confirm that tamoxifen has a direct effect on equine peripheral blood neutrophils, through stimulation of the engulfment of apoptotic neutrophils by alveolar macrophages.

Mitochondria in neutrophil apoptosis

NARCIS (Netherlands)

van Raam, B. J.; Verhoeven, A. J.; Kuijpers, T. W.

2006-01-01

Central in the regulation of the short life span of neutrophils are their mitochondria. These organelles hardly contribute to the energy status of neutrophils but play a vital role in the apoptotic process. Not only do the mitochondria contain cytotoxic proteins that are released during apoptosis

Neutrophil Responses to Sterile Implant Materials.

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Siddharth Jhunjhunwala

Full Text Available In vivo implantation of sterile materials and devices results in a foreign body immune response leading to fibrosis of implanted material. Neutrophils, one of the first immune cells to be recruited to implantation sites, have been suggested to contribute to the establishment of the inflammatory microenvironment that initiates the fibrotic response. However, the precise numbers and roles of neutrophils in response to implanted devices remains unclear. Using a mouse model of peritoneal microcapsule implantation, we show 30-500 fold increased neutrophil presence in the peritoneal exudates in response to implants. We demonstrate that these neutrophils secrete increased amounts of a variety of inflammatory cytokines and chemokines. Further, we observe that they participate in the foreign body response through the formation of neutrophil extracellular traps (NETs on implant surfaces. Our results provide new insight into neutrophil function during a foreign body response to peritoneal implants which has implications for the development of biologically compatible medical devices.

Neutrophil migration under normal and sepsis conditions.

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Lerman, Yelena V; Kim, Minsoo

2015-01-01

Neutrophil migration is critical for pathogen clearance and host survival during severe sepsis. Interaction of neutrophil adhesion receptors with ligands on endothelial cells results in firm adhesion of the circulating neutrophils, followed by neutrophil activation and directed migration to sites of infection through the basement membrane and interstitial extracellular matrix. Proteolytic enzymes and reactive oxygen species are produced and released by neutrophils in response to a variety of inflammatory stimuli. Although these mediators are important for host defense, they also promote tissue damage. Excessive neutrophil migration during the early stages of sepsis may lead to an exaggerated inflammatory response with associated tissue damage and subsequent organ dysfunction. On the other hand, dysregulation of migration and insufficient migratory response that occurs during the latter stages of severe sepsis contributes to neutrophils' inability to contain and control infection and impaired wound healing. This review discusses the major steps and associated molecules involved in the balance of neutrophil trafficking, the precise regulation of which during sepsis spells life or death for the host.

Mixed species biofilms of Fusobacterium necrophorum and Porphyromonas levii impair the oxidative response of bovine neutrophils in vitro.

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Lockhart, Joey S; Buret, Andre G; Ceri, Howard; Storey, Douglas G; Anderson, Stefanie J; Morck, Douglas W

2017-10-01

Biofilms composed of anaerobic bacteria can result in persistent infections and chronic inflammation. Host immune cells have difficulties clearing biofilm-related infections and this can result in tissue damage. Neutrophils are a vital component of the innate immune system and help clear biofilms. The comparative neutrophilic response to biofilms versus planktonic bacteria remains incompletely understood, particularly in the context of mixed infections. The objective of this study was to generate mixed species anaerobic bacterial biofilms composed of two opportunistic pathogens, Fusobacterium necrophorum and Porphyromonas levii, and evaluate neutrophil responses to extracellular fractions from both biofilms and planktonic cell co-cultures of the same bacteria. Purified bovine neutrophils exposed to culture supernatants from mixed species planktonic bacteria showed elevated oxidative activity compared to neutrophils exposed to biofilms composed of the same bacteria. Bacterial lipopolysaccharide plays a significant role in the stimulation of neutrophils; biofilms produced substantially more lipopolysaccharide than planktonic bacteria under these experimental conditions. Removal of lipopolysaccharide significantly reduced neutrophil oxidative response to culture supernatants of planktonic bacteria. Oxidative responses to LPS-removed biofilm supernatants and LPS-removed planktonic cell supernatants were similar. The limited neutrophil response to biofilm bacteria observed in this study supports the reduced ability of the innate immune system to eradicate biofilm-associated infections. Lipopolysaccharide is likely important in neutrophil response; however, the presence of other extracellular, immune modifying molecules in the bacterial media also appears to be important in altering neutrophil function. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Post-operative analgesia in case of ano-rectal diseases].

Science.gov (United States)

Rossitto, Maurizio; Pantè, Sebastiano; Manfrè, Antonino; Ciccolo, Antonio

2009-01-01

The aim of the study was that to evaluate the post-operative pain in case of ano-rectal diseases wether treated by ketorolac, or buprenorphine or tramadol. The intensity of post-operative pain was evaluated in 60 patients with hemorrhoidal diseases, fistulae, abscesses and anal neoplasms, divided into three homogenous groups and treated with intramuscular ketorolac (Group I), transdermal buprenorphine (Group II) and tramadol in elastomeric pump (Group III). The average index of the visual analogue scale, as mean to evaluate the intensity of the post-operative pain, was 1,85 in the first group, 1,20 in the second one and 1,40 in the third group. In patients treated with transdermal buprenorphine or with tramadol in elastomeric pump there has been a more quick psycho-physical recovery than in those treated with ketorolac; the management of elastomeric pump represents however for patients cause of concern while the transdermal system is a kind of rational and comfortable way of treatment of the pain, with the advantage of being non-invasive. Better compliance and lower operating costs have given the preference to the use of transdermal buprenorphine for the treatment of diseases of the post-operative pain in the diseases of the anal canal.

Association between elevated pre-operative glycosylated hemoglobin and post-operative infections after non-emergent surgery

OpenAIRE

Blankush, Joseph M.; Leitman, I. Michael; Soleiman, Aron; Tran, Trung

2016-01-01

Background: A chronic state of impaired glucose metabolism affects multiple components of the immune system, possibly leading to an increased incidence of post-operative infections. Such infections increase morbidity, length of stay, and overall cost. This study evaluates the correlation between elevated pre-operative glycosylated hemoglobin (HbA1c) and post-operative infections. Study design: Adult patients undergoing non-emergent procedures across all surgical subspecialties from January...

The control of neutrophil chemotaxis by inhibitors of cathepsin G and chymotrypsin.

Science.gov (United States)

Lomas, D A; Stone, S R; Llewellyn-Jones, C; Keogan, M T; Wang, Z M; Rubin, H; Carrell, R W; Stockley, R A

1995-10-06

Neutrophil chemotaxis plays an important role in the inflammatory response and when excessive or persistent may augment tissue damage. The effects of inhibitors indicated the involvement of one or more serine proteinases in human neutrophil migration and shape change in response to a chemoattractant. Monospecific antibodies, chloromethylketone inhibitors, and reactive-site mutants of alpha 1-antitrypsin and alpha 1-antichymotrypsin were used to probe the specificity of the proteinases involved in chemotaxis. Antibodies specific for cathepsin G inhibited chemotaxis. Moreover, rapid inhibitors of cathepsin G and alpha-chymotrypsin suppressed neutrophil chemotaxis to the chemoattractants N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) and zymosan-activated serum in multiple blind well assays and to fMLP in migration assays under agarose. The concentrations of antichymotrypsin mutants that reduced chemotaxis by 50% would inactivate free cathepsin G with a half-life of 1.5-3 s, whereas the concentrations of chloromethylketones required to produce a similar inhibition of chemotaxis would inactivate cathepsin G with a half-life of 345 s. These data suggest different modes of action for these two classes of inhibitors. Indeed the chloromethylketone inhibitors of cathepsin G (Z-Gly-Leu-Phe-CMK) and to a lesser extent of chymotrypsin (Cbz-Gly-Gly-Phe-CMK) mediated their effect by preventing a shape change in the purified neutrophils exposed to fMLP. Antichymotrypsin did not affect shape change in response to fMLP even at concentrations that were able to reduce neutrophil chemotaxis by 50%. These results support the involvement of cell surface proteinases in the control of cell migration and show that antichymotrypsin and chloromethylketones have differing modes of action. This opens the possibility for the rational design of anti-inflammatory agents targeted at neutrophil membrane enzymes.

Pathogenesis of post-irradiation infection. 2. Role of neutrophils in the defence of irradiated rats against Yersinia enterocolitica

International Nuclear Information System (INIS)

Bazin, Herve; Platteau, Bernadette; Bakour, Rabah; Janssens, Michele; Wauters, Georges

1982-01-01

Wistar R inbred rats showed a substantial mortality when they were given Yersinia enterocolitica eight days after a 6.5 Gy total body irradiation. The possibility to abolish the high susceptibility of these irradiated rats to Yersinia enterocolitica by intravenous injections of isogenic neutrophils is presented: irradiated rats injected with 7 to 10.10 7 isogenic neutrophils, by the intravenous route, just before or after the administration of Yersinia enterocolitica, were not susceptible. On the contrary, control irradiated rats, not transfused, were killed by the same bacterial challenge [fr

Pathogenesis of post-irradiation infection. 2. Role of neutrophils in the defence of irradiated rats against Yersinia enterocolitica

Energy Technology Data Exchange (ETDEWEB)

Bazin, H.; Platteau, B.; Bakour, R.; Janssens, M.; Wauters, G. (Universite de Louvain, Bruxelles (Belgium))

1982-07-01

Wistar R inbred rats showed a substantial mortality when they were given Yersinia enterocolitica eight days after a 6.5 Gy total body irradiation. The possibility to abolish the high susceptibility of these irradiated rats to Yersinia enterocolitica by intravenous injections of isogenic neutrophils is presented: irradiated rats injected with 7 to 10.10/sup 7/ isogenic neutrophils, by the intravenous route, just before or after the administration of Yersinia enterocolitica, were not susceptible. On the contrary, control irradiated rats, not transfused, were killed by the same bacterial challenge.

Choice reaction time in patients with post-operative cognitive dysfunction

DEFF Research Database (Denmark)

Steinmetz, J.; Rasmussen, L.S.

2008-01-01

BACKGROUND: Post-operative cognitive dysfunction (POCD) is detected by administration of a neuropsychological test battery. Reaction time testing is at present not included as a standard test. Choice reaction time (CRT) data from the first International Study of Post-operative Cognitive Dysfunction...... in nine countries. CRT was measured 52 times using the four boxes test. Patients performed the test before surgery (n=1083), at 1 week (n=926) and at 3 months (n=852) post-operatively. CRT for the individual patient was determined as the median time of correct responses. The usefulness of the CRT...... had a significantly longer CRT. ROC curves revealed that a reaction time of 813 ms was the most appropriate cut-off at 1 week and 762 ms at 3 months but the positive predictive value for POCD was low: 34.4% and 14.7%, respectively. CONCLUSIONS: Post-operative cognitive dysfunction is associated...

What Drive the Damage to Post-Merger Operating Performance?

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Soegiharto Soegiharto

2010-05-01

Full Text Available This study examines whether bidders’ post-merger operat-ing performance are affected by their CEO behavior, premiumspaid to the target firms, the period of mergers, the method ofpayment, the industry of merged firms, capital liquidity, andtheir pre-merger operating performance. Testing the U.S. suc-cessful merger and acquisition data for the period of 1990s, thisstudy finds that in-wave mergers, intra-industry mergers, thepayment of lower premiums, and better pre-merger operatingperformance drive the bidders to produce better post-mergeroperating performance. Three measures of CEO behavior—themain predictor scrutinezed in this study—are proposed andexamined, and the results demonstrate that the effects of thesemeasures on post-merger operating performance are mixed,suggesting that each of the behavioral measures designed in thisstudy may capture CEO behavior in different ways. Keywords: capital liquidity; CEO overconfidence; merger waves, method of pay-ment operating performance

Targeting Neutrophilic Inflammation Using Polymersome-Mediated Cellular Delivery.

Science.gov (United States)

Robertson, James D; Ward, Jon R; Avila-Olias, Milagros; Battaglia, Giuseppe; Renshaw, Stephen A

2017-05-01

Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In this study, we deliver therapeutic compounds to neutrophils using biocompatible, nanometer-sized synthetic vesicles, or polymersomes, which are internalized by binding to scavenger receptors and subsequently escape the early endosome through a pH-triggered disassembly mechanism. This allows polymersomes to deliver molecules into the cell cytosol of neutrophils without causing cellular activation. After optimizing polymersome size, we show that polymersomes can deliver the cyclin-dependent kinase inhibitor (R)-roscovitine into human neutrophils to promote apoptosis in vitro. Finally, using a transgenic zebrafish model, we show that encapsulated (R)-roscovitine can speed up inflammation resolution in vivo more efficiently than the free drug. These results show that polymersomes are effective intracellular carriers for drug delivery into neutrophils. This has important consequences for the study of neutrophil biology and the development of neutrophil-targeted therapeutics. Copyright © 2017 The Authors.

Neutrophil Reverse Migration Becomes Transparent with Zebrafish

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Taylor W. Starnes

2012-01-01

Full Text Available The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.

Crucial involvement of tumor-associated neutrophils in the regulation of chronic colitis-associated carcinogenesis in mice.

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Kun Shang

Full Text Available Ulcerative colitis (UC is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC. However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM, followed by repeated dextran sulfate sodium (DSS ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP-9 and neutrophil elastase (NE, accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2-CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer.

Crucial Involvement of Tumor-Associated Neutrophils in the Regulation of Chronic Colitis-Associated Carcinogenesis in Mice

Science.gov (United States)

Wang, Chen; Wang, Zhen; Gu, Hong-Yu; Du, Xiang; Zhou, Xiao-Yan; Zheng, Chun-Lei; Chi, Ya-Yun; Mukaida, Naofumi; Li, Ying-Yi

2012-01-01

Ulcerative colitis (UC) is a major form of chronic inflammation that can frequently progress to colon cancer. Several studies have demonstrated massive infiltration of neutrophils and macrophages into the lamina propria and submucosa in the progression of UC-associated colon carcinogenesis. Macrophages contribute to the development of colitis-associated colon cancer (CAC). However, the role of neutrophils is not well understood. To better understand the involvement of tumor-associated neutrophils (TANs) in the regulation of CAC, we used a mouse CAC model produced by administering azoxymethane (AOM), followed by repeated dextran sulfate sodium (DSS) ingestion. This causes severe colonic inflammation and subsequent development of multiple tumors in mice colon. We observed that colorectal mucosal inflammation became increasingly severe with AOM and DSS treatment. Macrophages infiltrated the lamina propria and submucosa, together with a marked increase in neutrophil infiltration. The chemokine CXCL2 increased in the lamina propria and submucosal regions of the colons of the treated mice, together with the infiltration of neutrophils expressing CXCR2, a specific receptor for CXCL2. This process was followed by neoplastic transformation. After AOM and DSS treatment, the mice showed enhanced production of metalloproteinase (MMP)-9 and neutrophil elastase (NE), accompanied by excessive vessel generation and cell proliferation. Moreover, CXCL2 promoted neutrophil recruitment and induced neutrophils to express MMP-9 and NE in vitro. Furthermore, administration of neutrophil-neutralizing antibodies after the last DSS cycle markedly reduced the number and size of tumors and decreased the expression of CXCR2, CXCL2, MMP-9, and NE. These observations indicate a crucial role for TANs in the initiation and progression of CAC and suggest that the CXCL2–CXCR2 axis might be useful in reducing the risk of UC-associated colon cancer. PMID:23272179

Anti-Inflammatory benefits of antibiotic-induced neutrophil apoptosis: tulathromycin induces caspase-3-dependent neutrophil programmed cell death and inhibits NF-kappaB signaling and CXCL8 transcription.

Science.gov (United States)

Fischer, Carrie D; Beatty, Jennifer K; Zvaigzne, Cheryl G; Morck, Douglas W; Lucas, Merlyn J; Buret, A G

2011-01-01

Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 × 10(7) CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B(4) in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IκBα, nuclear translocation of NF-κB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which

Comparison of the effect of pre- and post-operative physical therapy versus post-operative physical therapy alone on pain and recovery of function after total knee arthroplasty

OpenAIRE

Alghadir, Ahmad; Iqbal, Zaheen Ahmed; Anwer, Shahnawaz

2016-01-01

[Purpose] The aim of the present study was to compare the effect of pre-operative and post-operative physical therapy versus post-operative physical therapy alone on pain and recovery of function after total knee arthroplasty. [Subjects and Methods] Fifty patients (18 males and 32 females) ranging in age from 48 to 80?years (mean 63.28, SD 9.44) participated in a 6-week two-arm randomized rater-blinded trial. One group received pre- and post-operative physical therapy whereas the other group ...

Soluble CD40 ligand stimulates CD40-dependent activation of the β2 integrin Mac-1 and protein kinase C zeda (PKCζ in neutrophils: implications for neutrophil-platelet interactions and neutrophil oxidative burst.

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Rong Jin

Full Text Available Recent work has revealed an essential involvement of soluble CD40L (sCD40L in inflammation and vascular disease. Activated platelets are the major source of sCD40L, which has been implicated in platelet and leukocyte activation, although its exact functional impact on leukocyte-platelet interactions and the underlying mechanisms remain undefined. We aimed to determine the impact and the mechanisms of sCD40L on neutrophils. We studied neutrophil interactions with activated, surface-adherent platelets as a model for leukocyte recruitment to the sites of injury. Our data show that CD40L contributes to neutrophil firm adhesion to and transmigration across activated surface-adherent platelets, possibly through two potential mechanisms. One involves the direct interaction of ligand-receptor (CD40L-CD40, i.e., platelet surface CD40L interaction with neutrophil CD40; another involves an indirect mechanism, i.e. soluble CD40L stimulates activation of the leukocyte-specific β2 integrin Mac-1 in neutrophils and thereby further promotes neutrophil adhesion and migration. Activation of the integrin Mac-1 is known to be critical for mediating neutrophil adhesion and migration. sCD40L activated Mac-1 in neutrophils and enhanced neutrophil-platelet interactions in wild-type neutrophils, but failed to elicit such responses in CD40-deficient neutrophils. Furthermore, our data show that the protein kinase C zeta (PKCζ is critically required for sCD40L-induced Mac-1 activation and neutrophil adhesive function. sCD40L strongly stimulated the focal clustering of Mac-1 (CD11b and the colocalization of Mac-1 with PKCζ in wild-type neutrophils, but had minimal effect in CD40-deficient neutrophils. Blocking PKCζ completely inhibited sCD40L-induced neutrophil firm adhesion. Moreover, sCD40L strongly stimulates neutrophil oxidative burst via CD40-dependent activation of PI3K/NF-KB, but independent of Mac-1 and PKCζ. These findings may contribute to a better

Prediction of post-operative pain after a laparoscopic tubal ligation procedure

DEFF Research Database (Denmark)

Rudin, A.; Wolner-Hanssen, P.; Hellbom, M.

2008-01-01

ligation procedure. METHODS: Assessments of anxiety, mood, psychological vulnerability and pre-operative pain were made before surgery using the State-Trait Anxiety Inventory (STAI), the Hospital Anxiety Depression Scale (HADS), a psychological vulnerability test and the Short-Form McGill Pain......BACKGROUND: Pre-operative identification of reliable predictors of post-operative pain may lead to improved pain management strategies. We investigated the correlation between pre-operative pain, psychometric variables, response to heat stimuli and post-operative pain following a laparoscopic tubal...... Questionnaire (SF-MPQ), respectively. Pre-operative assessments of thermal thresholds and pain response to randomized series of heat stimuli (1 s, 44-48 degrees C) were made with quantitative sensory testing technique. Post-operative pain intensity was evaluated daily by a visual analogue scale during rest...

Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.

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Massimo Conese

Full Text Available In seeking more specific biomarkers of the cystic fibrosis (CF lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1, hydrogen voltage-gated channel 1 (HVCN1, and β-arrestin 1 (ARRB1. The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils

Evaluation of genome-wide expression profiles of blood and sputum neutrophils in cystic fibrosis patients before and after antibiotic therapy.

Science.gov (United States)

Conese, Massimo; Castellani, Stefano; Lepore, Silvia; Palumbo, Orazio; Manca, Antonio; Santostasi, Teresa; Polizzi, Angela Maria; Copetti, Massimiliano; Di Gioia, Sante; Casavola, Valeria; Guerra, Lorenzo; Diana, Anna; Montemurro, Pasqualina; Mariggiò, Maria Addolorata; Gallo, Crescenzio; Maffione, Angela Bruna; Carella, Massimo

2014-01-01

In seeking more specific biomarkers of the cystic fibrosis (CF) lung inflammatory disease that would be sensitive to antibiotic therapy, we sought to evaluate the gene expression profiles of neutrophils in CF patients before treatment in comparison with non-CF healthy individuals and after antibiotic treatment. Genes involved in neutrophil-mediated inflammation, i.e. chemotaxis, respiratory burst, apoptosis, and granule exocytosis, were the targets of this study. Microarray analysis was carried out in blood and airway neutrophils from CF patients and in control subjects. A fold change (log) threshold of 1.4 and a cut-off of p<0.05 were utilized to identify significant genes. Community networks and principal component analysis were used to distinguish the groups of controls, pre- and post-therapy patients. Control subjects and CF patients before therapy were readily separated, whereas a clear distinction between patients before and after antibiotic therapy was not possible. Blood neutrophils before therapy presented 269 genes down-regulated and 56 up-regulated as compared with control subjects. Comparison between the same patients before and after therapy showed instead 44 genes down-regulated and 72 up-regulated. Three genes appeared to be sensitive to therapy and returned to "healthy" condition: phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), hydrogen voltage-gated channel 1 (HVCN1), and β-arrestin 1 (ARRB1). The up-regulation of these genes after therapy were confirmed by real time PCR. In airway neutrophils, 1029 genes were differentially expressed post- vs pre-therapy. Of these, 30 genes were up-regulated and 75 down-regulated following antibiotic treatment. However, biological plausibility determined that only down-regulated genes belonged to the gene classes studied for blood neutrophils. Finally, it was observed that commonly expressed genes showed a greater variability in airway neutrophils than that found in blood neutrophils, both before and

Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection

International Nuclear Information System (INIS)

Ramsay, Stuart C.; Maggs, Jacqueline A.; Ketheesan, Natkunam; Norton, Robert; LaBrooy, Justin

2005-01-01

Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid ( 99m Tc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99m Tc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor

Urinary tract infections and post-operative fever in percutaneous nephrolithotomy

DEFF Research Database (Denmark)

Gutierrez, Jorge; Smith, Arthur; Geavlete, Petrisor

2013-01-01

PURPOSE: To review the incidence of UTIs, post-operative fever, and risk factors for post-operative fever in PCNL patients. MATERIALS AND METHODS: Between 2007 and 2009, consecutive PCNL patients were enrolled from 96 centers participating in the PCNL Global Study. Only data from patients with pre...

Targeting Neutrophilic Inflammation using Polymersome-Mediated Cellular Delivery

OpenAIRE

Robertson, J.D.; Ward, J.R.; Avila-Olias, M.; Battaglia, G.; Renshaw, S.A.

2017-01-01

Neutrophils are key effector cells in inflammation and play an important role in neutralizing invading pathogens. During inflammation resolution, neutrophils undergo apoptosis before they are removed by macrophages, but if apoptosis is delayed, neutrophils can cause extensive tissue damage and chronic disease. Promotion of neutrophil apoptosis is a potential therapeutic approach for treating persistent inflammation, yet neutrophils have proven difficult cells to manipulate experimentally. In ...

Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide.

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Sumioka, Ryuichi; Nakata, Masanobu; Okahashi, Nobuo; Li, Yixuan; Wada, Satoshi; Yamaguchi, Masaya; Sumitomo, Tomoko; Hayashi, Mikako; Kawabata, Shigetada

2017-01-01

Streptococcus is the dominant bacterial genus in the human oral cavity and a leading cause of infective endocarditis. Streptococcus sanguinis belongs to the mitis group of streptococci and produces hydrogen peroxide (H2O2) by the action of SpxB, a pyruvate oxidase. In this study, we investigated the involvement of SpxB in survival of S. sanguinis in human blood and whether bacterial H2O2 exhibits cytotoxicity against human neutrophils. Results of a bactericidal test with human whole blood revealed that the spxB mutation in S. sanguinis is detrimental to its survival in blood. When S. sanguinis strains were exposed to isolated neutrophils, the bacterial survival rate was significantly decreased by spxB deletion. Furthermore, human neutrophils exposed to the S. sanguinis wild-type strain, in contrast to those exposed to an spxB mutant strain, underwent cell death with chromatin de-condensation and release of web-like extracellular DNA, reflecting induction of neutrophil extracellular traps (NETs). Since reactive oxygen species-mediated NET induction requires citrullination of arginine residues in histone proteins and subsequent chromatin de-condensation, we examined citrullination levels of histone in infected neutrophils. It is important to note that the citrullinated histone H3 was readily detected in neutrophils infected with the wild-type strain, as compared to infection with the spxB mutant strain. Moreover, decomposition of streptococcal H2O2 with catalase reduced NET induction. These results suggest that H2O2 produced by S. sanguinis provokes cell death of neutrophils and NET formation, thus potentially affecting bacterial survival in the bloodstream.

Streptococcus sanguinis induces neutrophil cell death by production of hydrogen peroxide.

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Ryuichi Sumioka

Full Text Available Streptococcus is the dominant bacterial genus in the human oral cavity and a leading cause of infective endocarditis. Streptococcus sanguinis belongs to the mitis group of streptococci and produces hydrogen peroxide (H2O2 by the action of SpxB, a pyruvate oxidase. In this study, we investigated the involvement of SpxB in survival of S. sanguinis in human blood and whether bacterial H2O2 exhibits cytotoxicity against human neutrophils. Results of a bactericidal test with human whole blood revealed that the spxB mutation in S. sanguinis is detrimental to its survival in blood. When S. sanguinis strains were exposed to isolated neutrophils, the bacterial survival rate was significantly decreased by spxB deletion. Furthermore, human neutrophils exposed to the S. sanguinis wild-type strain, in contrast to those exposed to an spxB mutant strain, underwent cell death with chromatin de-condensation and release of web-like extracellular DNA, reflecting induction of neutrophil extracellular traps (NETs. Since reactive oxygen species-mediated NET induction requires citrullination of arginine residues in histone proteins and subsequent chromatin de-condensation, we examined citrullination levels of histone in infected neutrophils. It is important to note that the citrullinated histone H3 was readily detected in neutrophils infected with the wild-type strain, as compared to infection with the spxB mutant strain. Moreover, decomposition of streptococcal H2O2 with catalase reduced NET induction. These results suggest that H2O2 produced by S. sanguinis provokes cell death of neutrophils and NET formation, thus potentially affecting bacterial survival in the bloodstream.

GROUP B STREPTOCOCCUS CIRCUMVENTS NEUTROPHILS AND NEUTROPHIL EXTRACELLULAR TRAPS DURING AMNIOTIC CAVITY INVASION AND PRETERM LABOR

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Boldenow, Erica; Gendrin, Claire; Ngo, Lisa; Bierle, Craig; Vornhagen, Jay; Coleman, Michelle; Merillat, Sean; Armistead, Blair; Whidbey, Christopher; Alishetti, Varchita; Santana-Ufret, Veronica; Ogle, Jason; Gough, Michael; Srinouanprachanh, Sengkeo; MacDonald, James W; Bammler, Theo K; Bansal, Aasthaa; Liggitt, H. Denny; Rajagopal, Lakshmi; Waldorf, Kristina M Adams

2016-01-01

Preterm birth is a leading cause of neonatal morbidity and mortality. Although microbial invasion of the amniotic cavity (MIAC) is associated with the majority of early preterm births, the temporal events that occur during MIAC and preterm labor are not known. Group B Streptococci (GBS) are β-hemolytic, gram-positive bacteria, which commonly colonize the vagina but have been recovered from the amniotic fluid in preterm birth cases. To understand temporal events that occur during MIAC, we utilized a unique chronically catheterized nonhuman primate model that closely emulates human pregnancy. This model allows monitoring of uterine contractions, timing of MIAC and immune responses during pregnancy-associated infections. Here, we show that adverse outcomes such as preterm labor, MIAC, and fetal sepsis were observed more frequently during infection with hemolytic GBS when compared to nonhemolytic GBS. Although MIAC was associated with systematic progression in chorioamnionitis beginning with chorionic vasculitis and progressing to neutrophilic infiltration, the ability of the GBS hemolytic pigment toxin to induce neutrophil cell death and subvert killing by neutrophil extracellular traps (NETs) in placental membranes in vivo facilitated MIAC and fetal injury. Furthermore, compared to maternal neutrophils, fetal neutrophils exhibit decreased neutrophil elastase activity and impaired phagocytic functions to GBS. Collectively, our studies demonstrate how a unique bacterial hemolytic lipid toxin enables GBS to circumvent neutrophils and NETs in placental membranes to induce fetal injury and preterm labor. PMID:27819066

Study of Bacteriology of Post-Operative Wound Infection

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Neelam Abdulrauf Bagwan

2014-07-01

Full Text Available Background: While many patients are admitted to hospital for treatment of infections, some acquire infection during their stay in the hospital. These infections are called as nosocomial infections. Surgical site infection or post operative wound infection is one of them. It is defined as infection of previously sterile tissue incised to gain exposure for operating deeper spaces operatively exposed or organs manipulated by a surgeon. It is one of the feared complications of surgery as it increases morbidity as well as cost of medical care. Aims and Objectives: Study was conducted to find out incidence of surgical site infection rate in surgical ward, evaluate various factors contributing to infection and to identify causative pathogens and their antibiogram patterns. Material and Methods: All clean and clean contaminated operative cases admitted in surgery ward in study period of 18 months were included. Preoperative, operative and postoperative management protocols of the cases were recorded in detail. Results: A total of 1082 operated cases were studied among which 59 infected cases were found. Surgical Site Infection (SSI rate was 5.45%. E. coli and Staphylococcus aureus were the commonest pathogen isolated from the infected wound. 50 % were Methicillin Resistant Staphylococcus Aureus (MRSA among them and 50% of rd Enterobacteriaceae group were resistant to 3 generation Cephalosporins. Conclusion: Surgical site infection rate of a hospital can be reduced easily by following proper pre-operative protocol for the patients. Those patients with surgical site infection can be treated effectively by following the antibiotic policy as provided by the Department of Microbiology.

Differential Effect of Viable Versus Necrotic Neutrophils on Mycobacterium tuberculosis Growth and Cytokine Induction in Whole Blood

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David M. Lowe

2018-04-01

Full Text Available Neutrophils exert both positive and negative influences on the host response to tuberculosis, but the mechanisms by which these differential effects are mediated are unknown. We studied the impact of live and dead neutrophils on the control of Mycobacterium tuberculosis using a whole blood bioluminescence-based assay, and assayed supernatant cytokine concentrations using Luminex™ technology and ELISA. CD15+ granulocyte depletion from blood prior to infection with M. tuberculosis-lux impaired control of mycobacteria by 96 h, with a greater effect than depletion of CD4+, CD8+, or CD14+ cells (p < 0.001. Augmentation of blood with viable granulocytes significantly improved control of mycobacteria by 96 h (p = 0.001, but augmentation with necrotic granulocytes had the opposite effect (p = 0.01. Both augmentations decreased supernatant concentrations of tumor necrosis factor and interleukin (IL-12 p40/p70, but necrotic granulocyte augmentation also increased concentrations of IL-10, G-CSF, GM-CSF, and CCL2. Necrotic neutrophil augmentation reduced phagocytosis of FITC-labeled M. bovis BCG by all phagocytes, whereas viable neutrophil augmentation specifically reduced early uptake by CD14+ cells. The immunosuppressive effect of dead neutrophils required necrotic debris rather than supernatant. We conclude that viable neutrophils enhance control of M. tuberculosis in blood, but necrotic neutrophils have the opposite effect—the latter associated with induction of IL-10, growth factors, and chemoattractants. Our findings suggest a mechanism by which necrotic neutrophils may exert detrimental effects on the host response in active tuberculosis.

Effect of adductor-canal-blockade on established, severe post-operative pain after total knee arthroplasty

DEFF Research Database (Denmark)

Jaeger, P; Grevstad, Ulrik; Henningsen, Maja

2012-01-01

In this proof-of-concept study, we investigated the effect of the predominantly sensory adductor-canal-blockade on established pain in the early post-operative period after total knee arthroplasty (TKA). We hypothesised that the adductor-canal-blockade would reduce pain during flexion of the knee...... (primary end point) and at rest, as well as reducing morphine consumption and morphine-related side effects (secondary outcomes) compared with placebo....

Sexy again: the renaissance of neutrophils in psoriasis.

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Schön, Michael P; Broekaert, Sigrid M C; Erpenbeck, Luise

2017-04-01

Notwithstanding their prominent presence in psoriatic skin, the functional role of neutrophilic granulocytes still remains somewhat enigmatic. Sparked by exciting scientific discoveries regarding neutrophil functions within the last years, the interest in these short-lived cells of the innate immune system has been boosted recently. While it had been known for some time that neutrophils produce and respond to a number of inflammatory mediators, recent research has linked neutrophils with the pathogenic functions of IL-17, possibly in conjunction with the formation of NETs (neutrophil extracellular traps). Antipsoriatic therapies exert their effects, at least in part, through interference with neutrophils. Neutrophils also appear to connect psoriasis with comorbid diseases. However, directly tampering with neutrophil functions is not trivial as evinced by the failure of therapeutic approaches targeting redundantly regulated cellular communication networks. It has also become apparent that neutrophils link important pathogenic functions of the innate and the adaptive immune system and that they are intricately involved in regulatory networks underlying the pathophysiology of psoriasis. In order to advocate intensified research into the role of this interesting cell population, we here highlight some features of neutrophils and put them into perspective with our current view of the pathophysiology of psoriasis. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ensemble models of neutrophil trafficking in severe sepsis.

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Sang Ok Song

Full Text Available A hallmark of severe sepsis is systemic inflammation which activates leukocytes and can result in their misdirection. This leads to both impaired migration to the locus of infection and increased infiltration into healthy tissues. In order to better understand the pathophysiologic mechanisms involved, we developed a coarse-grained phenomenological model of the acute inflammatory response in CLP (cecal ligation and puncture-induced sepsis in rats. This model incorporates distinct neutrophil kinetic responses to the inflammatory stimulus and the dynamic interactions between components of a compartmentalized inflammatory response. Ensembles of model parameter sets consistent with experimental observations were statistically generated using a Markov-Chain Monte Carlo sampling. Prediction uncertainty in the model states was quantified over the resulting ensemble parameter sets. Forward simulation of the parameter ensembles successfully captured experimental features and predicted that systemically activated circulating neutrophils display impaired migration to the tissue and neutrophil sequestration in the lung, consequently contributing to tissue damage and mortality. Principal component and multiple regression analyses of the parameter ensembles estimated from survivor and non-survivor cohorts provide insight into pathologic mechanisms dictating outcome in sepsis. Furthermore, the model was extended to incorporate hypothetical mechanisms by which immune modulation using extracorporeal blood purification results in improved outcome in septic rats. Simulations identified a sub-population (about 18% of the treated population that benefited from blood purification. Survivors displayed enhanced neutrophil migration to tissue and reduced sequestration of lung neutrophils, contributing to improved outcome. The model ensemble presented herein provides a platform for generating and testing hypotheses in silico, as well as motivating further experimental

Cost-effectiveness of Crohn’s disease post-operative care

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Wright, Emily K; Kamm, Michael A; Dr Cruz, Peter; Hamilton, Amy L; Ritchie, Kathryn J; Bell, Sally J; Brown, Steven J; Connell, William R; Desmond, Paul V; Liew, Danny

2016-01-01

AIM: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn’s disease following intestinal resection. METHODS: In the “POCER” study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo. RESULTS: Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented. CONCLUSION: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated. PMID:27076772

National audit of post-operative management in spinal surgery

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Dicken Ben

2006-05-01

Full Text Available Abstract Background There is some evidence from a Cochrane review that rehabilitation following spinal surgery may be beneficial. Methods We conducted a survey of current post-operative practice amongst spinal surgeons in the United Kingdom in 2002 to determine whether such interventions are being included routinely in the post-operative management of spinal patients. The survey included all surgeons who were members of either the British Association of Spinal Surgeons (BASS or the Society for Back Pain Research. Data on the characteristics of each surgeon and his or her current pattern of practice and post-operative care were collected via a reply-paid postal questionnaire. Results Usable responses were provided by 57% of the 89 surgeons included in the survey. Most surgeons (79% had a routine post-operative management regime, but only 35% had a written set of instructions that they gave to their patients concerning this. Over half (55% of surgeons do not send their patients for any physiotherapy after discharge, with an average of less than two sessions of treatment organised by those that refer for physiotherapy at all. Restrictions on lifting, sitting and driving showed considerable inconsistency both between surgeons and also within the recommendations given by individual surgeons. Conclusion Demonstrable inconsistencies within and between spinal surgeons in their approaches to post-operative management can be interpreted as evidence of continuing and significant uncertainty across the sub-speciality as to what does constitute best care in these areas of practice. Conducting further large, rigorous, randomised controlled trials would be the best method for obtaining definitive answers to these questions.

Neutrophil chemotactic activity in bronchoalveolar lavage fluid of patients with AIDS-associated Pneumocystis carinii pneumonia

DEFF Research Database (Denmark)

Benfield, T L; Kharazmi, A; Larsen, C G

1997-01-01

been shown to confer a poor prognosis in PCP. We therefore investigated the potential of BAL fluid from 17 patients with PCP to induce neutrophil chemotaxis. BAL fluid from patients induced considerable neutrophil chemotactic activity compared to normal controls. Elevated levels of IL-8 were detected...... in patient samples as compared to controls. A specific anti-IL-8 antibody significantly reduced chemotactic activity of patient samples by more than 50%. In conclusion, IL-8 appears to be a significant participant of neutrophil chemotaxis in AIDS-associated PCP, and may participate in the recruitment...

Neutrophils in Cancer: Two Sides of the Same Coin.

Science.gov (United States)

Uribe-Querol, Eileen; Rosales, Carlos

2015-01-01

Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs) have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Efficacy of post-operative radiotherapy in the treatment of breast cancer

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Api, P; Corcione, S; Magnoni, G

1985-01-01

A clinical evaluation regarding the efficacy of post-operative radiotherapy in 294 patients with breast cancer is presented. In the author's opinion post-operative radiotherapy is fundamental in the treatment of this tumor. 21 refs.

Hepatic Warm Ischemia-Reperfusion-Induced Increase in Pulmonary Capillary Filtration Is Ameliorated by Administration of a Multidrug Resistance-Associated Protein 1 Inhibitor and Leukotriene D4 Antagonist (MK-571) Through Reducing Neutrophil Infiltration and Pulmonary Inflammation and Oxidative Stress in Rats.

Science.gov (United States)

Yeh, D Y-W; Yang, Y-C; Wang, J-J

2015-05-01

Hepatopulmonary syndrome (HPS) is the major complication subsequent to liver ischemia and reperfusion (I/R) injury after resection or transplantation of liver. Hallmarks of HPS include increases in pulmonary leukotrienes and neutrophil recruitment and infiltrating across capillaries. We aimed to investigate the protective efficacy of MK-571, a multidrug resistance-associated protein 1 inhibitor and leukotriene D4 agonist, against hepatic I/R injury-associated change in capillary filtration. Eighteen Sprague-Dawley male rats were evenly divided into a sham-operated group, a hepatic I/R group, and an MK-571-treated I/R group. MK-571 was administered intraperitoneally 15 min before hepatic ischemia and every 12 hours during reperfusion. Ischemia was conducted by occluding the hepatic artery and portal vein for 30 min, followed by removing the clamps and closing the incision. Forty-eight hours after hepatic ischemia, we assessed the pulmonary capillary filtration coefficient (Kfc) through the use of in vitro-isolated, perfused rat lung preparation. We also measured the lung wet-to-dry weight ratio (W/D) and protein concentration in broncho-alveolar lavage fluid (PCBAL). Lung inflammation and oxidative stress were evaluated by use of tissue tumor necrosis factor (TNF)-α and malondialdehyde levels and lavage differential macrophage and neutrophil cell count. Hepatic I/R injury markedly increased Kfc, W/D, PCBAL, tissue TNF-α level, and differential neutrophil cell count (P < .05). MK-571 treatment reduced neutrophil infiltration and lung inflammation and improved pulmonary capillary filtration, collectively suggesting lung protection. Treatment with MK-571 before and during hepatic ischemia and reperfusion protects lung against pulmonary capillary barrier function impairment through decreasing pulmonary lung inflammation and lavage neutrophils. Copyright © 2015 Elsevier Inc. All rights reserved.

Regulation of neutrophil senescence by microRNAs.

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Jon R Ward

2011-01-01

Full Text Available Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease.

Neutrophils in Cancer: Two Sides of the Same Coin

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Eileen Uribe-Querol

2015-01-01

Full Text Available Neutrophils are the most abundant leukocytes in blood and are considered to be the first line of defense during inflammation and infections. In addition, neutrophils are also found infiltrating many types of tumors. Tumor-associated neutrophils (TANs have relevant roles in malignant disease. Indeed neutrophils may be potent antitumor effector cells. However, increasing clinical evidence shows TANs correlate with poor prognosis. The tumor microenvironment controls neutrophil recruitment and in turn TANs help tumor progression. Hence, TANs can be beneficial or detrimental to the host. It is the purpose of this review to highlight these two sides of the neutrophil coin in cancer and to describe recent studies that provide some light on the mechanisms for neutrophil recruitment to the tumor, for neutrophils supporting tumor progression, and for neutrophil activation to enhance their antitumor functions.

Radiation-induced muscositis and neutrophil granulocytes in oral mucosa; Strahleninduzierte Mukositis und neutrophile Granulozyten in der Mundschleimhaut

Energy Technology Data Exchange (ETDEWEB)

Schmidberger, H.; Rave-Fraenk, M.; Kim, S.; Hille, A.; Pradier, O.; Hess, C.F. [Klinik fuer Strahlentherapie und Radioonkologie, Univ. Goettingen (Germany)

2003-10-01

Background: Chemotherapy-induced mucositis can be related to a decrease in oral neutrophils. We tested the relationship between radiation-induced mucositis and oral neutrophil counts. Patients and Methods: Oral neutrophil counts were obtained for ten patients with head and neck cancer who received radiotherapy of the pharynx and oral cavity. Four patients received additional chemotherapy (5-FU, Mitomycin). Counts were obtained before and during treatment; four healthy volunteers were included in the study as well. For evaluation, a quantitative mouth rinse assay, including neutrophil-staining with acridin-orange, was applied. Results: We observed large inter-individual variations with respect to neutrophil counts for patients and control persons (Table 1). During treatment (irradiation or chemoirradiation), large intra-individual variations were seen additionally (Figure 1). We found a correlation between neutrophil counts and clinical reaction grade. Neutrophil counts increased with increasing mucositis (Figure 2). This increase was more pronounced for patients treated with chemoirradiation compared to radiation alone. Treatment breaks at weekends had no clear influence on neutrophil counts. Conclusions: We observed a weak correlation between neutrophil counts and clinical reaction grade. However, the variations in neutrophil counts are too large to utilize this parameter as a surrogate for clinical mucositis grading. The assumption that a decrease in oral neutrophils is associated with radiation-induced mucositis was clearly negated. (orig.) [German] Hintergrund: Die chemotherapieinduzierte Mukositis kann mit einer Verarmung der Mundschleimhaut an neutrophilen Granulozyten vergesellschaftet sein. Wir ueberprueften den Zusammenhang zwischen der radiogenen Mukositis und der Anzahl neutrophiler Granulozyten. Patienten und Methoden: Bei zehn Patienten mit Tumoren der Kopf-Hals-Region, die sich einer Strahlentherapie unterzogen, wurde die Anzahl enoraler neutrophiler

Improved recovery of functionally active eosinophils and neutrophils using novel immunomagnetic technology.

Science.gov (United States)

Son, Kiho; Mukherjee, Manali; McIntyre, Brendan A S; Eguez, Jose C; Radford, Katherine; LaVigne, Nicola; Ethier, Caroline; Davoine, Francis; Janssen, Luke; Lacy, Paige; Nair, Parameswaran

2017-10-01

Clinically relevant and reliable reports derived from in vitro research are dependent on the choice of cell isolation protocols adopted between different laboratories. Peripheral blood eosinophils are conventionally isolated using density-gradient centrifugation followed by immunomagnetic selection (positive/negative) while neutrophils follow a more simplified dextran-sedimentation methodology. With the increasing sophistication of molecular techniques, methods are now available that promise protocols with reduced user-manipulations, improved efficiency, and better yield without compromising the purity of enriched cell populations. These recent techniques utilize immunomagnetic particles with multiple specificities against differential cell surface markers to negatively select non-target cells from whole blood, greatly reducing the cost/time taken to isolate granulocytes. Herein, we compare the yield efficiencies, purity and baseline activation states of eosinophils/neutrophils isolated using one of these newer protocols that use immunomagnetic beads (MACSxpress isolation) vs. the standard isolation procedures. The study shows that the MACSxpress method consistently allowed higher yields per mL of peripheral blood compared to conventional methods (Peosinophils (95.0±1.7%) and neutrophils (94.2±10.1%) assessed by two methods: Wright's staining and flow cytometry. In addition, enumeration of CD63 + (marker for eosinophil activation) and CD66b + (marker for neutrophil activation) cells within freshly isolated granulocytes, respectively, confirmed that conventional protocols using density-gradient centrifugation caused cellular activation of the granulocytes at baseline compared to the MACSxpress method. In conclusion, MACSxpress isolation kits were found to be superior to conventional techniques for consistent purifications of eosinophils and neutrophils that were suitable for activation assays involving degranulation markers. Copyright © 2017 Elsevier B.V. All

5 CFR 831.631 - Post-retirement election of fully reduced annuity or partially reduced annuity to provide a...

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2010-01-01

... annuity or partially reduced annuity to provide a current spouse annuity. 831.631 Section 831.631...) RETIREMENT Survivor Annuities Post-Retirement Elections § 831.631 Post-retirement election of fully reduced annuity or partially reduced annuity to provide a current spouse annuity. (a) Except as provided in...

Delayed diagnosis of post-surgical pyoderma gangrenosum: A multicenter case series and review of literature

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Rawaa Almukhtar

Full Text Available Introduction: Pyoderma gangrenosum is a chronic neutrophilic dermatosis which can occur following trauma or surgery and can mimic infection. Surgical intervention can lead to progression of disease. Presentation of cases: This case series describes 3 cases of post-surgical pyoderma gangrenosum with delayed diagnosis from two large medical centers. Discussion: Epidemiology, pathogenesis, clinical and histopathologic presentation, and management of post-surgical pyoderma gangrenosum are discussed with a review of the literature. Conclusion: Post-surgical pyoderma gangrenosum (PSPG can mimic ulcerative disorders including bacterial infection. The diagnosis should be suspected in post-operative wounds with negative bacterial cultures which progress despite broad-spectrum antibiotics and surgical debridement. Recognizing the clinical features of PSPG is fundamental to prevent severe destruction and deformity. Keywords: Post-surgical, Pyoderma gangrenosum, Necrotizing fasciitis, Case report

Neutrophils in Tuberculosis: Heterogeneity Shapes the Way?

Science.gov (United States)

2017-01-01

Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease. PMID:28626346

5 CFR 831.632 - Post-retirement election of fully reduced annuity or partially reduced annuity to provide a...

Science.gov (United States)

2010-01-01

... annuity or partially reduced annuity to provide a former spouse annuity. 831.632 Section 831.632...) RETIREMENT Survivor Annuities Post-Retirement Elections § 831.632 Post-retirement election of fully reduced annuity or partially reduced annuity to provide a former spouse annuity. (a)(1) Except as provided in...

Hepatobiliary transporter expression and post-operative jaundice in patients undergoing partial hepatectomy.

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Bernhardt, Gerwin A; Zollner, Gernot; Cerwenka, Herwig; Kornprat, Peter; Fickert, Peter; Bacher, Heinz; Werkgartner, Georg; Müller, Gabriele; Zatloukal, Kurt; Mischinger, Hans-Jörg; Trauner, Michael

2012-01-01

Post-operative hyperbilirubinaemia in patients undergoing liver resections is associated with high morbidity and mortality. Apart from different known factors responsible for the development of post-operative jaundice, little is known about the role of hepatobiliary transport systems in the pathogenesis of post-operative jaundice in humans after liver resection. Two liver tissue samples were taken from 14 patients undergoing liver resection before and after Pringle manoeuvre. Patients were retrospectively divided into two groups according to post-operative bilirubin serum levels. The two groups were analysed comparing the results of hepatobiliary transporter [Na-taurocholate cotransporter (NTCP); multidrug resistance gene/phospholipid export pump(MDR3); bile salt export pump (BSEP); canalicular bile salt export pump (MRP2)], heat shock protein 70 (HSP70) expression as well as the results of routinely taken post-operative liver chemistry tests. Patients with low post-operative bilirubin had lower levels of NTCP, MDR3 and BSEP mRNA compared to those with high bilirubin after Pringle manoeuvre. HSP70 levels were significantly higher after ischaemia-reperfusion (IR) injury in both groups resulting in 4.5-fold median increase. Baseline median mRNA expression of all four transporters prior to Pringle manoeuvre tended to be lower in the low bilirubin group whereas expression of HSP70 was higher in the low bilirubin group compared to the high bilirubin group. Higher mRNA levels of HSP70 in the low bilirubin group could indicate a possible protective effect of high HSP70 levels against IR injury. Although the exact role of hepatobiliary transport systems in the development of post-operative hyper bilirubinemia is not yet completely understood, this study provides new insights into the molecular aspects of post-operative jaundice after liver surgery. © 2011 John Wiley & Sons A/S.

Topical versus intravenous tranexamic acid as a blood conservation intervention for reduction of post-operative bleeding in hemiarthroplasty.

Science.gov (United States)

Emara, Walid Mohamed; Moez, Khaled K; Elkhouly, Abeer H

2014-01-01

This study was performed to test the effectiveness of topical tranexamic acid (TXA) in reducing blood loss in pelvic hemiarthoplasty surgeries compared with intravenous TXA, regarding the incidence of thromboembolic complications (deep vein thrombosis [DVT], pulmonary embolism (PE) and cerebrovascular stroke [CVS]). After obtaining institutional ethical approval 60 patients divided into three groups. Group A: Received intravenous TXA Group B: Received topical TXA Group C: Control group (placebo saline). All patients were received general anesthesia and post-operative bleeding, immediate and 24 h post-operatively, hemoglobin concentration, hematocrit, platelets and coagulation profile (prothrombin time, activated partial thromboplastin time and international normalized ratio) baseline, immediate and 24 h post-operatively. Thromboelastography was recorded baseline, immediate and 24 h post-operatively. Incidence of DVT, PE and CVS was recorded. There was statistical significant elevation hemoglobin concentration and hematocrit in both Groups A and B, significant increase in blood loss in Group C, significant increase in number of patients receiving blood in Group C, there was a significant decrease in "r" and "k" times and a significant increase in maximum amplitude and α-angle in Group A, statistically significant increase in the incidence of thromboembolic events in the form of DVT, PE and CVS in Group A. Topical TXA is effective in decreasing post-operative blood loss with possible side-effects of this route of administration.

Post-operative pain treatment in Denmark from 2000 to 2009

DEFF Research Database (Denmark)

Nielsen, P R; Christensen, P A; Meyhoff, C S

2012-01-01

In Denmark, the first acute pain service (APS) was introduced in 1993. An important objective became to facilitate implementation of accelerated post-operative rehabilitation programmes (ACC) in selected procedures in abdominal, gynaecological and orthopaedic surgery. Therefore......, it is of considerable interest to study the association between the developments of post-operative pain management and the ACC by sequential analyses from 2000 to 2009....

Pilot prospective study of post-surgery sleep and EEG predictors of post-operative delirium.

Science.gov (United States)

Evans, Joanna L; Nadler, Jacob W; Preud'homme, Xavier A; Fang, Eric; Daughtry, Rommie L; Chapman, Joseph B; Attarian, David; Wellman, Samuel; Krystal, Andrew D

2017-08-01

Delirium is a common post-operative complication associated with significant costs, morbidity, and mortality. We sought sleep/EEG predictors of delirium present prior to delirium symptoms to facilitate developing and targeting therapies. Continuous EEG data were obtained in 12 patients post-orthopedic surgery from the day of surgery until delirium assessment on post-operative day 2 (POD2). Diminished total sleep time (r=-0.68; pdelirium severity. Patients experiencing delirium slept 2.4h less and took 2h longer to fall asleep. Greater waking EEG delta power (r=0.84; pdelirium severity. Loss of sleep on night1 post-surgery is an early predictor of subsequent delirium. EEG Delta Power alterations in waking and sleep appear to be later indicators of impending delirium. Further work is needed to evaluate reproducibility/generalizability and assess whether sleep loss contributes to causing delirium. This first study to prospectively collect continuous EEG data for an extended period prior to delirium onset identified EEG-derived indices that predict subsequent delirium that could aid in developing and targeting therapies. Copyright © 2017. Published by Elsevier B.V.

Activation of bovine neutrophils by Brucella spp.

Science.gov (United States)

Keleher, Lauren L; Skyberg, Jerod A

2016-09-01

Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of whole-body X-radiation on the neutrophils of the peripheral blood of the primate Cebus apella (weeping capuchin)

International Nuclear Information System (INIS)

Egami, Mizue Imoto; Silva, Maria Regina Regis; Paiva, Elias Rodrigues de; Segreto, Camilo; Diniz, Lilian Munao

1994-01-01

The effects of ionizing radiation on the neutrophils of Primate Cebus apella were studied after whole-body x-radiation to a single exposure of 25.8 m C/kg (100 R 0, Wright's stained preparations showed changes in the nucleus and the cytoplasm of neutrophils at 1,3 and 6 days after irradiation. during this period of time, the cytochemical methods revealed a considerable variation in the pattern of distribution of glycogen, sudanophilic and myeloperoxidase positive granules. Under these same experimental conditions the number of caryoschizes increased on the first and third day. On the ninetieth day post exposure, the morphological and cytochemical appearances of neutrophils as well as the number of caryoschized were similar to the controls. (author)

Gene transfer and expression in human neutrophils. The phox homology domain of p47phox translocates to the plasma membrane but not to the membrane of mature phagosomes

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Brzezinska Agnieszka A

2006-12-01

Full Text Available Abstract Background Neutrophils are non-dividing cells with poor survival after isolation. Consequently, exogenous gene expression in neutrophils is challenging. We report here the transfection of genes and expression of active proteins in human primary peripheral neutrophils using nucleofection. Results Exogenous gene expression in human neutrophils was achieved 2 h post-transfection. We show that neutrophils transfected by nucleofection are functional cells, able to respond to soluble and particulate stimuli. They conserved the ability to undergo physiological processes including phagocytosis. Using this technique, we were able to show that the phox homology (PX domain of p47phox localizes to the plasma membrane in human neutrophils. We also show that RhoB, but not the PX domain of p47phox, is translocated to the membrane of mature phagosomes. Conclusion We demonstrated that cDNA transfer and expression of exogenous protein in human neutrophils is compatible with cell viability and is no longer a limitation for the study of protein function in human neutrophils.

The complex interplay between neutrophils and cancer.

Science.gov (United States)

Rakic, Andrea; Beaudry, Paul; Mahoney, Douglas J

2018-03-01

Neutrophils are the most abundant type of white blood cell, and are an essential component of the innate immune system. They characteristically arrive rapidly at sites of infection and injury, and release a variety of cytokines and toxic molecules to eliminate pathogens and elicit an acute inflammatory response. Research into the function of neutrophils in cancer suggest they have divergent roles. Indeed, while most studies have found neutrophils to be associated with cancer progression, others have also documented anticancer effects. In this review, we describe the investigations into neutrophil populations that have been implicated in promoting tumor growth and metastasis as well those demonstrating antitumor functions. The collective research suggests a complex role for neutrophils in cancer biology, which raises the prospect of their targeting for the treatment of cancer.

Pathophysiology of neutrophil-mediated extracellular redox reactions.

Science.gov (United States)

Jaganjac, Morana; Cipak, Ana; Schaur, Rudolf Joerg; Zarkovic, Neven

2016-01-01

Neutrophil granulocyte leukocytes (neutrophils) play fundamental role in the innate immune response. In the presence of adequate stimuli, neutrophils release excessive amount of reactive oxygen species (ROS) that may induce cell and tissue injury. Oxidative burst of neutrophils acts as a double-edged sword. It may contribute to the pathology of atherosclerosis and brain injury but is also necessary in resolving infections. Moreover, neutrophil-derived ROS may also have both a tumor promoting and tumor suppressing role. ROS have a specific activities and diffusion distance, which is related to their short lifetime. Therefore, the manner in which ROS will act depends on the cells targeted and the intra- and extracellular levels of individual ROS, which can further cause production of reactive aldehydes like 4-hydroxynonenal (HNE) that act as a second messengers of ROS. In this review we discuss the influence of neutrophil mediated extracellular redox reactions in ischemia reperfusion injury, transplant rejection and chronic diseases (atherosclerosis, inflammatory bowel diseases and cancer). At the end a brief overview of cellular mechanisms to maintain ROS homeostasis is given.

Localization and Functionality of the Inflammasome in Neutrophils

DEFF Research Database (Denmark)

Bakele, Martina; Joos, Melanie; Burdi, Sofia

2014-01-01

Neutrophils represent the major fraction of circulating immune cells and are rapidly recruited to sites of infection and inflammation. The inflammasome is a multiprotein complex that regulates the generation of IL-1 family proteins. The precise subcellular localization and functionality...... of the inflammasome in human neutrophils are poorly defined. Here we demonstrate that highly purified human neutrophils express key components of the NOD-like receptor family, pyrin domain containing 3 (NLRP3), and absent in melanoma 2 (AIM2) inflammasomes, particularly apoptosis-associated speck-like protein...... and released as protein, highly purified neutrophils neither expressed nor released IL-1α at baseline or upon stimulation. Upon inflammasome activation, highly purified neutrophils released substantially lower levels of IL-1β protein compared with partially purified neutrophils. Serine proteases and caspases...

Sevoflurane impairs post-operative olfactory memory but preserves olfactory function.

Science.gov (United States)

Kostopanagiotou, Georgia; Kalimeris, Konstantinos; Kesidis, Kyriakos; Matsota, Paraskevi; Dima, Cleanthi; Economou, Maria; Papageorgiou, Charalambos

2011-01-01

The effect of anaesthesia on olfaction has not been systematically studied. Our aim is to compare the effects of general and regional anaesthesia on olfactory acuity and memory in the immediate post-operative period. Sixty adult patients with the American Society of Anesthesiologists I and II status scheduled for elective minor surgery were included. Exclusion criteria were smoking, alcoholism, psychiatric disease and recent or past airway infection with resulting hyposmia. Patients were randomly allocated to one of three groups (in the analysis, n = 16 in each group): epidural anaesthesia (group E), general anaesthesia with propofol (group P) and general anaesthesia with sevoflurane (group S) of 40-120 min duration. The evening before surgery, at 0.5 and at 3 h post-operatively olfactory acuity and memory were tested, along with blood sampling to measure plasma melatonin and oxytocin levels. Olfactory acuity was tested with successive dilutions of n-butyl-alcohol, and olfactory memory (interpretation of odours) with the University of Pennsylvania Smell Identification Test. Patient characteristics did not differ between groups. Olfactory acuity was intact in all patients, before and after anaesthesia. Olfactory memory deteriorated in group S compared to groups P and E at both post-operative time-points. This was accompanied by a significant post-operative reduction of plasma melatonin levels in group S. Oxytocin levels remained constant in all groups. Our results manifest a specific effect of sevoflurane on olfactory memory, not observed with neuraxial or total intravenous anaesthesia. The misinterpretation of odours in the immediate post-operative period by sevoflurane could be mediated by the decreased levels of melatonin.

Enrofloxacin enhances the formation of neutrophil extracellular traps in bovine granulocytes

Science.gov (United States)

Jerjomiceva, Natalja; Seri, Hisham; Völlger, Lena; Wang, Yanming; Zeitouni, Nathalie; Naim, Hassan Y.; von Köckritz-Blickwede, Maren

2014-01-01

Several antibiotics are known for their ability to accumulate in neutrophils and thereby modulate the antimicrobial functions of those cells. This manuscript demonstrates for the first time that an antibiotic, namely the fluoroquinolone enrofloxacin, enhances the formation of bovine neutrophil extracellular traps (NETs). When pharmacologically inactivating NADPH oxidase or peptidylarginine deiminase-4, enrofloxacin-induced NET-formation was distinctly reduced. Additionally, when treating the cells with cytochalasin D or nocodazole, the enrofloxacin-mediated NET-induction was abolished, indicating that besides oxidative burst and histone citrullination also the actin and microtubule polymerization are involved in this process. PMID:24642685

Evaluation of post-operative prophylactic irradiation for carcinoma of the esophagus

International Nuclear Information System (INIS)

Mafune, Ken-ichi; Tanaka, Yoichi; Fujita, Kichishiro; Sakura, Mizuyoshi

1987-01-01

Of 147 patients with carcinoma of the esophagus resected at Saitama Cancer Center Hospital for 10 years, 98 cases were studied to evaluate post-operative prophylactic irradiation. The total dose of irradiation was up to 4,000 ∼ 5,000 rads of Linac X-ray and the irradiated field was T-shaped covering the upper mediastinal and bilateral cervical regions. The prognosis of the post-operative irradiated group (56 cases) was significantly better than that of the control group (42 cases) (p < 0.01). This study resulted in a five-year survival rate of 34.2 percent for patients in the post-operative irradiated group, compared to 16.7 percent for those in the control group. Further detailed comparative studies revealed similar results. Cancer recurrence occurred at the irradiated fields in 8 cases (14.3 %), though in 15 cases (35.7 %) of the control group. This suggested the local suppressive effect of the post-operative irradiation to the cancer recurrence. (author)

Age is the work of art? Impact of neutrophil and organism age on neutrophil extracellular trap formation.

Science.gov (United States)

Ortmann, Weronika; Kolaczkowska, Elzbieta

2018-03-01

Neutrophil extracellular traps or NETs are released by highly activated neutrophils in response to infectious agents, sterile inflammation, autoimmune stimuli and cancer. In the cells, the nuclear envelop disintegrates and decondensation of chromatin occurs that depends on peptidylarginine deiminase 4 (PAD4) and neutrophil elastase (NE). Subsequently, proteins from neutrophil granules (e.g., NE, lactoferrin and myeloperoxidase) and the nucleus (histones) bind to decondensed DNA and the whole structure is ejected from the cell. The DNA decorated with potent antimicrobials and proteases can act to contain dissemination of infection and in sterile inflammation NETs were shown to degrade cytokines and chemokines via serine proteases. On the other hand, overproduction of NETs, or their inadequate removal and prolonged presence in vasculature or tissues, can lead to bystander damage or even initiation of diseases. Considering the pros and cons of NET formation, it is of relevance if the stage of neutrophil maturation (immature, mature and senescent cells) affects the capacity to produce NETs as the cells of different age-related phenotypes dominate in given (pathological) conditions. Moreover, the immune system of neonates and elderly individuals is weaker than in adulthood. Is the same pattern followed when it comes to NETs? The overall importance of individual and neutrophil age on the capacity to release NETs is reviewed in detail and the significance of these facts is discussed.

Is peri-operative cortisol secretion related to post-operative cognitive dysfunction?

NARCIS (Netherlands)

Rasmussen, L.S.; O'Brien, J.T.; Silverstein, J.H.; Johnson, T.; Siersma, V.D.; Canet, J.; Jolles, J.; Hanning, C.D.; Kuipers, H.M.; Abildstrom, H.; Papaioannou, A.; Raeder, J.; Yli-Hankala, A.; Sneyd, J.R.; Munoz, L.; Moller, J.T.

2005-01-01

Background: The pattern of cortisol secretion is influenced by surgery. As cortisol can adversely affect neuronal function, this may be an important factor in the development of post-operative cognitive dysfunction (POCD). We hypothesized that the incidence of POCD would be related to changes in

Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

Science.gov (United States)

Pazos, Michael A; Lanter, Bernard B; Yonker, Lael M; Eaton, Alex D; Pirzai, Waheed; Gronert, Karsten; Bonventre, Joseph V; Hurley, Bryan P

2017-08-01

Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3), initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4). We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2) activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

Pseudomonas aeruginosa ExoU augments neutrophil transepithelial migration.

Directory of Open Access Journals (Sweden)

Michael A Pazos

2017-08-01

Full Text Available Excessive neutrophil infiltration of the lungs is a common contributor to immune-related pathology in many pulmonary disease states. In response to pathogenic infection, airway epithelial cells produce hepoxilin A3 (HXA3, initiating neutrophil transepithelial migration. Migrated neutrophils amplify this recruitment by producing a secondary gradient of leukotriene B4 (LTB4. We sought to determine whether this two-step eicosanoid chemoattractant mechanism could be exploited by the pathogen Pseudomonas aeruginosa. ExoU, a P. aeruginosa cytotoxin, exhibits phospholipase A2 (PLA2 activity in eukaryotic hosts, an enzyme critical for generation of certain eicosanoids. Using in vitro and in vivo models of neutrophil transepithelial migration, we evaluated the impact of ExoU expression on eicosanoid generation and function. We conclude that ExoU, by virtue of its PLA2 activity, augments and compensates for endogenous host neutrophil cPLA2α function, leading to enhanced transepithelial migration. This suggests that ExoU expression in P. aeruginosa can circumvent immune regulation at key signaling checkpoints in the neutrophil, resulting in exacerbated neutrophil recruitment.

Representation of functions as the Post-Widder inversion operator of generalized functions

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R. P. Manandhar

1984-01-01

Full Text Available A study is made of the Post-Widder inversion operator to a class of generalized functions in the sense of distributional convergence. Necessary and sufficient conditions are proved for a given function to have the representation as the rth operate of the Post-Widder inversion operator of generalized functions. Some representation theorems are also proved. Certain results concerning the testing function space and its dual are established. A fundamental theorem regarding the existence of the real inversion operator (1.6 with r=0 is proved in section 4. A classical inversion theory for the Post-Widder inversion operator with a few other theorems which are fundamental to the representation theory is also developed in this paper.

In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model.

Science.gov (United States)

Filio-Rodríguez, Georgina; Estrada-García, Iris; Arce-Paredes, Patricia; Moreno-Altamirano, María M; Islas-Trujillo, Sergio; Ponce-Regalado, M Dolores; Rojas-Espinosa, Oscar

2017-10-01

In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism. Guinea pigs were intradermally inoculated with M. tuberculosis H37Rv, and the production of NETs was investigated at several time points thereafter. NETs were detected as early as 30 min post-inoculation and were clearly evident by 4 h post-inoculation. NETs produced in vivo contained DNA, myeloperoxidase, elastase, histones, ROS and acid-fast bacilli. Viable and heat-killed M. tuberculosis, as well as Mycobacterium bovis BCG were efficient NET inducers, as were unilamellar liposomes prepared with lipids from M. tuberculosis. In vitro, guinea pig neutrophils also produced NETs in response to M. tuberculosis. However, neither the in vivo nor the in vitro-produced NETs were able to kill M. tuberculosis. Nevertheless, in vivo, neutrophils might propitiate recruitment and activation of more efficient microbicidal cells.

Cryptococcus neoformans modulates extracellular killing by neutrophils

Directory of Open Access Journals (Sweden)

Asfia eQureshi

2011-09-01

Full Text Available We recently established a key role for host sphingomyelin synthase (SMS in the regulation of the killing activity of neutrophils against Cryptococcus neoformans. In this work, we studied the effect of C. neoformans on the killing activity of neutrophils and whether SMS would still be a player against C. neoformans in immunocompromised mice lacking T and NK cells (Tgε26 mice. To this end, we analyzed whether C. neoformans would have any effect on neutrophil survival and killing in vitro and in vivo. We show that unlike C. albicans, neither the presence nor the capsule size of C. neoformans cells have any effect on neutrophil viability. Interestingly, melanized C. neoformans cells totally abrogated the killing activity of neutrophils. Next, we monitored how exposure of neutrophils to C. neoformans cells would interfere with any further killing activity of the medium and found that pre-incubation with live but not heat-killed fungal cells significantly inhibits further killing activity of the medium. We next studied whether activation of SMS at the site of C. neoformans infection is dependent on T and NK cells. Using matrix-assisted laser desorption-ionization (MALDI tissue imaging in infected lung we found that similarly to previous observations in the isogenic wild type CBA/J mice, SM 16:0 levels are significantly elevated at the site of infection in mice lacking T and NK cells but only at early time points. This study highlights that C. neoformans may negatively regulate the killing activity of neutrophils and that SMS activation in neutrophils appears to be partially independent of T and/or NK cells.

Assessment and validation of CT scanogram to compare per-operative and post-operative mechanical axis after navigated total knee replacement

Science.gov (United States)

Jain, Sunil

2008-01-01

Our objective was to assess and validate low-dose computed tomography (CT) scanogram as a post-operative imaging modality to measure the mechanical axis after navigated total knee replacement. A prospective study was performed to compare intra-operative and post-operative mechanical axis after navigated total knee replacements. All consecutive patients who underwent navigated total knee replacement between May and December 2006 were included. The intra-operative final axis was recorded, and post-operatively a CT scanogram of lower limbs was performed. The mechanical axis was measured and compared against the intra-operative measurement. There were 15 patients ranging in age from 57 to 80 (average 70) years. The average final intra-operative axis was 0.56° varus (4° varus to 1.5° valgus) and post-operative CT scanogram axis was 0.52° varus (3.1° varus to 1.8° valgus). The average deviation from final axes to CT scanogram axes was 0.12° valgus with a correlation coefficient of 0.9. Our study suggests that CT scanogram is an imaging modality with reasonable accuracy for measuring mechanical axis despite significantly low radiation. It also confirms a high level of correlation between intra-operative and post-operative mechanical axis after navigated total knee replacement. PMID:18696064

Contribution of neutrophils to acute lung injury.

Science.gov (United States)

Grommes, Jochen; Soehnlein, Oliver

2011-01-01

Treatment of acute lung injury (ALI) and its most severe form, acute respiratory distress syndrome (ARDS), remain unsolved problems of intensive care medicine. ALI/ARDS are characterized by lung edema due to increased permeability of the alveolar-capillary barrier and subsequent impairment of arterial oxygenation. Lung edema, endothelial and epithelial injury are accompanied by an influx of neutrophils into the interstitium and broncheoalveolar space. Hence, activation and recruitment of neutrophils are regarded to play a key role in progression of ALI/ARDS. Neutrophils are the first cells to be recruited to the site of inflammation and have a potent antimicrobial armour that includes oxidants, proteinases and cationic peptides. Under pathological circumstances, however, unregulated release of these microbicidal compounds into the extracellular space paradoxically can damage host tissues. This review focuses on the mechanisms of neutrophil recruitment into the lung and on the contribution of neutrophils to tissue damage in ALI.

Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

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Jitka Y. Sagiv

2015-02-01

Full Text Available Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs. LDNs consist of both immature myeloid-derived suppressor cells (MDSCs and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

Legionella phosphatase hydrolyzes phosphatidylinositol 4,5-bisphosphate and inosital triphosphate in human neutrophils

International Nuclear Information System (INIS)

Dowling, J.N.; Saha, A.K.; Glew, R.H.

1987-01-01

Legionella are facultative intracellular bacterial pathogens which multiply in host phagocytes. L. micdadei cells contain an acid phosphatase (ACP) that blocks superoxide anion production by human neutrophils stimulated with the formylated peptide, fMLP. The possibility that ACP acts by interefering with polyphosphoinositide metabolism and the production of the intracellular second messenger, inositol triphosphate (IP 3 ) was explored. When neutrophil phosphoinositides were labeled with 32 P, incubation of the cells with ACP caused an 85% loss of the labeled phosphatidylinositol-4,5-bisphosphate (PIP 2 ) over 2 h. Treatment of [ 3 H]inositol-labeled neutrophils with ACP for 30 min resulted in a 20% decrease of labeled PIP 2 . Following fMLP stimulation, the fractional reduction in PIP 2 and the fractional increase in IP 3 was the same in ACP-treated and untreated neutrophils, but the total quantity of IP 3 was reduced by ACP pre-treatment. The reduction in IP 3 generated following fMLP stimulation seems to be due primarily to the decreased amount of PIP 2 available for hydrolysis. However, some loss of IP 3 due to direct hydrolysis by ACP cannot be ruled out. The Legionella phosphatase may compromise neutrophil response to the bacteria by hydrolyzing PIP 2 , the prognitor of IP 3 , and by hydrolyzing IP 3 itself

Effect of induced subclinical hypocalcemia on physiological responses and neutrophil function in dairy cows.

Science.gov (United States)

Martinez, N; Sinedino, L D P; Bisinotto, R S; Ribeiro, E S; Gomes, G C; Lima, F S; Greco, L F; Risco, C A; Galvão, K N; Taylor-Rodriguez, D; Driver, J P; Thatcher, W W; Santos, J E P

2014-02-01

The objectives were to study the effects of induced subclinical hypocalcemia [SCH, blood ionized Ca (iCa(2+)) dairy cows. Ten nonpregnant, nonlactating Holstein cows were blocked by lactation and assigned randomly to a normocalcemic (NC; intravenous infusion of 0.9% NaCl i.v. plus 43 g of oral Ca, as Ca sulfate and Ca chloride, at -1 and 11h) or an induced SCH [SCHI, 5% ethylene glycol tetraacetic acid (EGTA), a selective iCa(2+) chelator, intravenous infusion] treatment for 24h, using a crossover design. The sequence of treatments was either NC-SCHI or SCHI-NC, with a 6-d washout period. Ionized Ca was evaluated before, hourly during the infusion period, and at 48 and 72 h, to monitor concentrations and adjust the rate of infusion, maintaining blood iCa(2+) insulin in plasma, and urinary excretion of Ca. Total and differential leukocyte count in blood was also performed. The concentration of cytosolic iCa(2+) in neutrophils and lymphocytes was quantified and neutrophil function was assayed in vitro. Infusion of a 5% EGTA solution successfully induced SCH in all SCHI cows, resulting in decreased blood iCa(2+) concentrations throughout the 24-h treatment period (0.77 ± 0.01 vs. 1.26 ± 0.01 mM iCa(2+)). Induction of SCH reduced dry matter intake on the day of infusion (5.3 ± 0.8 vs. 9.1 ± 0.8 kg/d) and rumen contractions (1.9 ± 0.2 vs. 2.7 ± 0.2 contractions/2 min) for the last 12h of infusion. Cows in SCHI had decreased plasma insulin concentration (1.44 ± 0.23 vs. 2.32 ± 0.23 ng/mL) evident between 6 and 18 h after the beginning of the infusion, accompanied by increased concentrations of glucose (4.40 ± 0.04 vs. 4.17 ± 0.04 mM). Plasma nonesterified fatty acids concentration was greater for SCHI than NC cows (0.110 ± 0.019 vs. 0.061 ± 0.014 mM). Neutrophils of cows in SCHI had a faster decrease in cytosolic iCa(2+) after stimulation with ionomycin (9.9 ± 1.0 vs. 13.6 ± 1.4 Fluo-4:Fura Red post-end ratio) in vitro. Furthermore, induction of SCH reduced

Angiogenic activity of bFGF and VEGF suppressed by proteolytic cleavage by neutrophil elastase

International Nuclear Information System (INIS)

Ai, Shingo; Cheng Xianwu; Inoue, Aiko; Nakamura, Kae; Okumura, Kenji; Iguchi, Akihisa; Murohara, Toyoaki; Kuzuya, Masafumi

2007-01-01

Neutrophil elastase (NE), a serine protease released from the azurophil granules of activated neutrophil, proteolytically cleaves multiple cytokines, and cell surface proteins. In the present study, we examined whether NE affects the biological abilities of angiogenic growth factors such as basic-fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). NE degraded bFGF and VEGF in a time- and concentration-dependent manner, and these degradations were suppressed by sivelestat, a synthetic inhibitor of NE. The bFGF- or VEGF-mediated proliferative activity of human umbilical vein endothelial cells was inhibited by NE, and the activity was recovered by sivelestat. Furthermore, NE reduced the bFGF- or VEGF-induced tubulogenic response of the mice aortas, ex vivo angiogenesis assay, and these effects were also recovered by sivelestat. Neutrophil-derived NE degraded potent angiogenic factors, resulting in loss of their angiogenic activity. These findings provide additional insight into the role played by neutrophils in the angiogenesis process at sites of inflammation

Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

DEFF Research Database (Denmark)

Sørensen, A L; Hey, A S; Kharazmi, A

1994-01-01

In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

Hidden truth of circulating neutrophils (polymorphonuclear neutrophil function in periodontally healthy smoker subjects

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Chitra Agarwal

2016-01-01

Full Text Available Context: Tobacco smoking is considered to be a major risk factor associated with periodontal disease. Smoking exerts a major effect on the protective elements of the immune response, resulting in an increase in the extent and severity of periodontal destruction. Aims: The aim of the present study was to assess viability and phagocytic function of neutrophils in circulating blood of the smokers and nonsmokers who are periodontally healthy. Settings and Design: Two hundred subjects in the mean range of 20–30 years of age were included in the study population. It was a retrospective study carried out for 6 months. Materials and Methods: Two hundred subjects were divided into four groups: 50 nonsmokers, 50 light smokers (15 cigarettes/day. Full mouth plaque index, sulcus bleeding index, and probing depths were measured. Percentage viability of circulating neutrophils and average number of phagocytosed Candida albicans were recorded. Statistical Analysis Used: Means and standard deviations were calculated from data obtained within the groups. Comparison between the smokers and nonsmokers was performed by Kruskal–Wallis ANOVA analysis. Comparison between smoker groups was performed using Mann–Whitney–Wilcoxon test. Results: Percentage viability of neutrophils was significantly less in heavy smokers (66.9 ± 4.0, moderate (76.6 ± 4.2, light smokers (83.1 ± 2.5 as compared to nonsmokers (92.3 ± 2.6 (P < 0.01. The ability of neutrophils to phagocytose, i.e., mean particle number was significantly less in light smokers (3.5 ± 0.5, moderate smokers (2.3 ± 0.5, and heavy smokers (1.4 ± 0.5 compared to nonsmokers (4.9 ± 0.7 (P < 0.01 with evidence of dose-response effect. Conclusions: Smoking significantly affects neutrophils viability and phagocytic function in periodontally healthy population.

An evaluation of intra-operative and post-operative blood loss in ...

African Journals Online (AJOL)

Background: Total knee replacement is a rewarding and reliable procedure, producing a lasting relief to severe knee pains. However, significant blood loss usually in the post-operative period may be a challenge, necessitating prompt restoration of circulating blood volume to minimize morbidity and mortality. The aim of this ...

Mitigating Hillslope Erosion After Post-fire Salvage Logging Operations

Science.gov (United States)

Robichaud, P. R.; Bone, E. D.; Brown, R. E.

2017-12-01

In the past decades, wildfires around the world have continued to increase in size, severity, and cost. Major concerns after wildfires are the increased runoff and erosion due to loss of the protective forest floor layer, loss of water storage, and creation of water repellent soil conditions. Salvage logging is often a post-fire forest management action to recoup the economic loss of the burned timber, yet concerns arise on the impacts of this activity on water quality. Recently, several studies have been conducted to determine the effect of salvage logging on hillslope erosion. Logging skid trails have been cited as being the cause of high erosion during and after salvage operations. We investigated the impacts of adding operational logging slash to skid trails to reduce hillslope erosion after salvage operations on the 2015 North Star Fire, Washington. We implemented well-designed rapid response approach to compare slash treatment effectiveness by monitoring sediment yield and runoff response from hillslopes with a concentrated flow (rill) experiment. Various runoff amounts are incrementally added to 4 m hillslope plots with and without slash treatments. Our initial results suggest that adding logging slash increased ground cover significantly which contributed to an order of magnitude decrease in hillslope erosion. Integrating erosion mitigation strategies into salvage logging operations should be commonplace when hillslope erosion is a concern.

Biomaterial-induced alterations of neutrophil superoxide production.

Science.gov (United States)

Kaplan, S S; Basford, R E; Mora, E; Jeong, M H; Simmons, R L

1992-08-01

Because periprosthetic infection remains a vexing problem for patients receiving implanted devices, we evaluated the effect of several materials on neutrophil free radical production. Human peripheral blood neutrophils were incubated with several sterile, lipopolysaccharide (LPS)-free biomaterials used in surgically implantable prosthetic devices: polyurethane, woven dacron, and velcro. Free radical formation as the superoxide (O2-) anion was evaluated by cytochrome c reduction in neutrophils that were exposed to the materials and then removed and in neutrophils allowed to remain in association with the materials. Neutrophils exposed to polyurethane or woven dacron for 30 or 60 min and then removed consistently exhibited an enhanced release of O2- after simulation via receptor engagement with formyl methionyl-leucyl-phenylalanine. Enhanced reactivity to stimulation via protein kinase C with phorbol myristate acetate, however, was not consistently observed. The cells evaluated for O2- release during continuous association with the biomaterials showed enhanced metabolic activity during short periods of association (especially with polyurethane and woven dacron). Although O2- release by neutrophils in association with these materials decreased with longer periods of incubation, it was not obliterated. These studies, therefore, show that several commonly used biomaterials activate neutrophils soon after exposure and that this activated state diminishes with prolonged exposure but nevertheless remains measurable. The diminishing level of activity with prolonged exposure, however, suggests that ultimately a depletion of reactivity may occur and may result in increased susceptibility to periprosthetic infection.

Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

Science.gov (United States)

Song, Hyun-Ouk; Ryu, Jae-Sook

2013-08-01

Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

The effect of pre-operative optimization on post-operative outcome in Crohn's disease resections

DEFF Research Database (Denmark)

El-Hussuna, Alaa; Iesalnieks, Igors; Horesh, Nir

2017-01-01

BACKGROUND: The timing of surgical intervention in Crohn's disease (CD) may depend on pre-operative optimization (PO) which includes different interventions to decrease the risk for unfavourable post-operative outcome. The objective of this study was to investigate the effect of multi-model PO on...

Advanced Role of Neutrophils in Common Respiratory Diseases

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Jinping Liu

2017-01-01

Full Text Available Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD, pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

Is the Time of administration of misoprostol of value? The uterotonic effect of misoprostol given pre- and post-operative after elective cesarean section

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Ahmed H. Abd-Ellah

2014-03-01

Conclusion: Pre-operative rectally administrated misoprostol appears to be more effective than post-operative rectally administrated misoprostol in reducing blood loss, and in decreasing the need for other uterotonic drugs in cesarean section delivery.

Characterization of Yersinia pestis Interactions with Human Neutrophils In vitro

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Sophia C. Dudte

2017-08-01

Full Text Available Yersinia pestis is a gram-negative, zoonotic, bacterial pathogen, and the causative agent of plague. The bubonic form of plague occurs subsequent to deposition of bacteria in the skin by the bite of an infected flea. Neutrophils are recruited to the site of infection within the first few hours and interactions between neutrophils and Y. pestis have been demonstrated in vivo. In contrast to macrophages, neutrophils have been considered non-permissive to Y. pestis intracellular survival. Several studies have shown killing of the vast majority of Y. pestis ingested by human neutrophils. However, survival of 10–15% of Y. pestis after phagocytosis by neutrophils is consistently observed. Furthermore, these surviving bacteria eventually replicate within and escape from the neutrophils. We set out to further characterize the interactions between Y. pestis and human neutrophils by (1 determining the effects of known Y. pestis virulence factors on bacterial survival after uptake by neutrophils, (2 examining the mechanisms employed by the neutrophil to kill the majority of intracellular Y. pestis, (3 determining the activation phenotype of Y. pestis-infected neutrophils, and (4 characterizing the Y. pestis-containing phagosome in neutrophils. We infected human neutrophils in vitro with Y. pestis and assayed bacterial survival and uptake. Deletion of the caf1 gene responsible for F1 capsule production resulted in significantly increased uptake of Y. pestis. Surprisingly, while the two-component regulator PhoPQ system is important for survival of Y. pestis within neutrophils, pre-induction of this system prior to infection did not increase bacterial survival. We used an IPTG-inducible mCherry construct to distinguish viable from non-viable intracellular bacteria and determined the association of the Y. pestis-containing phagosome with neutrophil NADPH-oxidase and markers of primary, secondary and tertiary granules. Additionally, we show that inhibition of

Outcome of peri-anal surgeries without use of prophylactic antibiotics, in terms of post operative wound infection

International Nuclear Information System (INIS)

Asif, M.; Mirza, A.A.; Saeed, A.

2017-01-01

To determine the outcome of perianal surgeries without use of antibiotics in terms of post operative infection. Study Design: Descriptive study. Place and Duration of study: Department of general surgery, Pakistan Atomic Energy Commission General Hospital, from Jan 2014 to Jun 2015. Material and Methods: All patients, both male and female admitted for hemorrhoidectomy, fistulectomy and lateral internal sphincterotomy for Anal Fissure with minimum 02 months follow-up were included in the study through non probability consecutive sampling technique. The selected patients were not administered any antibiotics pre or postoperatively. All these patients were followed up for any post-operative surgical site infection up to 02 months. Patients were advised only to take pyodine sitz bath regularly. Results: One hundred and eighty two patients were selected for the study. Patients mean age was 48.0 +- 11.4 years. 68.68% were male and 31.3% were female patients. In our study most frequent clinical presentation was hemorrhoids (37.9.0%), followed by anal fissure (33.5%). Least frequent clinical presentation was of anal fistula (28.57%). None of the patients developed surgical site infection post operatively. Conclusions: In our study we found that there was no additional beneficial role of prophylactic antibiotics in perianal surgeries Perianal surgeries can safely be performed without the use pre or post-operative antibiotics there by significantly reducing health care expenses. (author)

Neutrophil extracellular trap formation in supragingival biofilms.

Science.gov (United States)

Hirschfeld, Josefine; Dommisch, Henrik; Skora, Philipp; Horvath, Gabor; Latz, Eicke; Hoerauf, Achim; Waller, Tobias; Kawai, Toshihisa; Jepsen, Søren; Deschner, James; Bekeredjian-Ding, Isabelle

2015-01-01

Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1β and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter

Reducing elevator energy use: A comparison of posted feedback and reduced elevator convenience

Science.gov (United States)

Houten, Ron Van; Nau, Paul A.; Merrigan, Michael

1981-01-01

The effects of two different procedures for reducing elevator energy use were assessed using a multiple-baseline design. In the first procedure, feedback about the amount of energy consumed by the elevators each week was posted on each elevator door. Later, signs advocating the use of stairs to save energy and improve health were posted next to the feedback signs. In the second procedure, the time required to travel between floors was increased by adding a delay to the elevator door closing mechanisms. Results indicated that neither feedback alone nor feedback plus educational signs reduced the amount of energy consumed by the elevators. However, use of the door delay reduced consumption by one-third in all elevators. A second experiment replicated the effect of the door delay on energy consumption and, in addition, demonstrated that the door delay also produced a reduction in the number of persons using the elevator. The second experiment also showed that, following an initial period during which a full delay was in effect, a gradual reduction of the delay interval resulted in continued energy conservation. Reduced convenience as a general strategy for energy conservation is discussed. PMID:16795648

Potent inhibition of human neutrophil activations by bractelactone, a novel chalcone from Fissistigma bracteolatum

Energy Technology Data Exchange (ETDEWEB)

Wu, Yang-Chang [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 404, Taiwan (China); Sureshbabu, Munisamy; Fang, Yao-Ching; Wu, Yi-Hsiu [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Lan, Yu-Hsuan [School of Pharmacy, China Medical University, Taichung 404, Taiwan (China); Chang, Fang-Rong [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Ya-Wen [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Hwang, Tsong-Long, E-mail: htl@mail.cgu.edu.tw [Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan (China)

2013-02-01

Fissistigma bracteolatum is widely used in traditional medicine to treat inflammatory diseases. However, its active components and mechanisms of action remain unclear. In this study, (3Z)-6,7-dihydroxy-4-methoxy-3-(phenylmethylidene)-5-(3-phenylpropanoyl) -1-benzofuran-2(3H) (bractelactone), a novel chalcone from F. bracteolatum, showed potent inhibitory effects against superoxide anion (O{sub 2}{sup ·−}) production, elastase release, and CD11b expression in formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP)-induced human neutrophils. However, bractelactone showed only weak inhibition of phorbol myristate acetate-caused O{sub 2}{sup ·−} production. The peak cytosolic calcium concentration ([Ca{sup 2+}]{sub i}) was unaltered by bractelactone in FMLP-induced neutrophils, but the decay time of [Ca{sup 2+}]{sub i} was significantly shortened. In a calcium-free solution, changes in [Ca{sup 2+}]{sub i} caused by the addition of extracellular Ca{sup 2+} were inhibited by bractelactone in FMLP-activated cells. In addition, bractelactone did not alter the phosphorylation of p38 MAPK, ERK, JNK, or AKT or the concentration of cAMP. These results suggest that bractelactone selectively inhibits store-operated calcium entry (SOCE). In agreement with this concept, bractelactone suppressed sustained [Ca{sup 2+}]{sub i} changes in thapsigargin-activated neutrophils. Furthermore, bractelactone did not alter FMLP-induced formation of inositol 1,4,5-triphosphate. Taken together, our results demonstrate that the anti-inflammatory effects of bractelactone, an active ingredient of F. bracteolatum, in human neutrophils are through the selective inhibition of SOCE. Highlights: ► Bractelactone isolated from Fissistigma bracteolatum. ► Bractelactone inhibited FMLP-induced human neutrophil activations. ► Bractelactone had no effect on IP3 formation. ► Bractelactone did not alter MAPKs, AKT, and cAMP pathways. ► Bractelactone inhibited store-operated calcium entry.

A Journey to Zero: Reduction of Post-Operative Cesarean Surgical Site Infections over a Five-Year Period

OpenAIRE

Hickson, Evelyn; Harris, Jeanette; Brett, David

2015-01-01

Background: Surgical site infections (SSI) are a substantial concern for cesarean deliveries in which a surgical site complication is most unwelcome for a mother with a new infant. Steps taken pre- and post-operatively to reduce the number of complications may be of substantial benefit clinically, economically, and psychologically.

Staphylococcus aureus penetrate the interkeratinocyte spaces created by skin-infiltrating neutrophils in a mouse model of impetigo.

Science.gov (United States)

Imanishi, Ichiro; Hattori, Shinpei; Hisatsune, Junzo; Ide, Kaori; Sugai, Motoyuki; Nishifuji, Koji

2017-02-01

Impetigo is a bacterial skin disease characterized by intraepidermal neutrophilic pustules. Previous studies have demonstrated that exfoliative toxin producing staphylococci are isolated in the cutaneous lesions of human and canine impetigo. However, the mechanisms of intraepidermal splitting in impetigo remain poorly understood. To determine how staphylococci penetrate the living epidermis and create intraepidermal pustules in vivo using a mouse model of impetigo. Three Staphylococcus aureus strains harbouring the etb gene and three et gene negative strains were epicutaneously inoculated onto tape-stripped mouse skin. The skin samples were subjected to time course histopathological and immunofluorescence analyses to detect intraepidermal neutrophils and infiltrating staphylococci. To determine the role of neutrophils on intraepidermal bacterial invasion, cyclophosphamide (CPA) was injected intraperitoneally into the mice to cause leucopenia before the inoculation of etb gene positive strains. In mice inoculated with etb gene positive S. aureus, intraepidermal pustules resembling impetigo were detected as early as 4 h post-inoculation (hpi). Neutrophils in the epidermis were detected from 4 hpi, whereas intraepidermal staphylococci was detected from 6 hpi. The dimensions of the intraepidermal clefts created in mice inoculated with etb gene positive strains at 6 hpi were significantly larger than those in mice inoculated with et gene negative strains. In CPA treated mice, staphylococci or neutrophils were not detected in the deep epidermis until 6 hpi. Our findings indicate that intraepidermal neutrophils play an important role in S. aureus invasion into the living epidermis in a mouse model of impetigo. © 2016 ESVD and ACVD.

Candida albicans escapes from mouse neutrophils

DEFF Research Database (Denmark)

Ermert, David; Niemiec, Maria J; Röhm, Marc

2013-01-01

is the most widely used model organism. Neutrophils are essential immune cells to prevent opportunistic mycoses. To explore potential differences between the rodent infection model and the human host, we compared the interactions of C. albicans with neutrophil granulocytes from mice and humans. We revealed...

Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation.

Science.gov (United States)

Alemán, Omar Rafael; Mora, Nancy; Cortes-Vieyra, Ricarda; Uribe-Querol, Eileen; Rosales, Carlos

2016-01-01

Neutrophils (PMN) are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs) to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA) are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

Differential Use of Human Neutrophil Fcγ Receptors for Inducing Neutrophil Extracellular Trap Formation

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Omar Rafael Alemán

2016-01-01

Full Text Available Neutrophils (PMN are the most abundant leukocytes in the blood. PMN migrate from the circulation to sites of infection, where they are responsible for antimicrobial functions. PMN use phagocytosis, degranulation, and formation of neutrophil extracellular traps (NETs to kill microbes. NETs are fibers composed of chromatin and neutrophil-granule proteins. Several pathogens, including bacteria, fungi, and parasites, and also some pharmacological stimuli such as phorbol 12-myristate 13-acetate (PMA are efficient inducers of NETs. Antigen-antibody complexes are also capable of inducing NET formation. However the particular Fcγ receptor involved in triggering this function is a matter of controversy. In order to provide some insight into what Fcγ receptor is responsible for NET formation, each of the two human Fcγ receptors was stimulated individually by specific monoclonal antibodies and NET formation was evaluated. FcγRIIa cross-linking did not promote NET formation. Cross-linking other receptors such as integrins also did not promote NET formation. In contrast FcγRIIIb cross-linking induced NET formation similarly to PMA stimulation. NET formation was dependent on NADPH-oxidase, PKC, and ERK activation. These data show that cross-linking FcγRIIIb is responsible for NET formation by the human neutrophil.

Activated Protein C Attenuates Severe Inflammation by Targeting VLA-3high Neutrophil Subpopulation in Mice.

Science.gov (United States)

Sarangi, Pranita P; Lee, Hyun-Wook; Lerman, Yelena V; Trzeciak, Alissa; Harrower, Eric J; Rezaie, Alireza R; Kim, Minsoo

2017-10-15

The host injury involved in multiorgan system failure during severe inflammation is mediated, in part, by massive infiltration and sequestration of hyperactive neutrophils in the visceral organ. A recombinant form of human activated protein C (rhAPC) has shown cytoprotective and anti-inflammatory functions in some clinical and animal studies, but the direct mechanism is not fully understood. Recently, we reported that, during endotoxemia and severe polymicrobial peritonitis, integrin VLA-3 (CD49c/CD29) is specifically upregulated on hyperinflammatory neutrophils and that targeting the VLA-3 high neutrophil subpopulation improved survival in mice. In this article, we report that rhAPC binds to human neutrophils via integrin VLA-3 (CD49c/CD29) with a higher affinity compared with other Arg-Gly-Asp binding integrins. Similarly, there is preferential binding of activated protein C (PC) to Gr1 high CD11b high VLA-3 high cells isolated from the bone marrow of septic mice. Furthermore, specific binding of rhAPC to human neutrophils via VLA-3 was inhibited by an antagonistic peptide (LXY2). In addition, genetically modified mutant activated PC, with a high affinity for VLA-3, shows significantly improved binding to neutrophils compared with wild-type activated PC and significantly reduced neutrophil infiltration into the lungs of septic mice. These data indicate that variants of activated PC have a stronger affinity for integrin VLA-3, which reveals novel therapeutic possibilities. Copyright © 2017 by The American Association of Immunologists, Inc.

Osthol attenuates neutrophilic oxidative stress and hemorrhagic shock-induced lung injury via inhibition of phosphodiesterase 4.

Science.gov (United States)

Tsai, Yung-Fong; Yu, Huang-Ping; Chung, Pei-Jen; Leu, Yann-Lii; Kuo, Liang-Mou; Chen, Chun-Yu; Hwang, Tsong-Long

2015-12-01

Oxidative stress caused by neutrophils is an important pathogenic factor in trauma/hemorrhagic (T/H)-induced acute lung injury (ALI). Osthol, a natural coumarin found in traditional medicinal plants, has therapeutic potential in various diseases. However, the pharmacological effects of osthol in human neutrophils and its molecular mechanism of action remain elusive. In this study, our data showed that osthol potently inhibited the production of superoxide anion (O2(•-)) and reactive oxidants derived therefrom as well as expression of CD11b in N-formylmethionylleucylphenylalanine (FMLP)-activated human neutrophils. However, osthol inhibited neutrophil degranulation only slightly and it failed to inhibit the activity of subcellular NADPH oxidase. FMLP-induced phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (Akt) was inhibited by osthol. Notably, osthol increased the cAMP concentration and protein kinase A (PKA) activity in activated neutrophils. PKA inhibitors reversed the inhibitory effects of osthol, suggesting that these are mediated through cAMP/PKA-dependent inhibition of ERK and Akt activation. Furthermore, the activity of cAMP-specific phosphodiesterase (PDE) 4, but not PDE3 or PDE7, was significantly reduced by osthol. In addition, osthol reduced myeloperoxidase activity and pulmonary edema in rats subjected to T/H shock. In conclusion, our data suggest that osthol has effective anti-inflammatory activity in human neutrophils through the suppression of PDE4 and protects significantly against T/H shock-induced ALI in rats. Osthol may have potential for future clinical application as a novel adjunct therapy to treat lung inflammation caused by adverse circulatory conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Hypoxia upregulates neutrophil degranulation and potential for tissue injury

Science.gov (United States)

Hoenderdos, Kim; Lodge, Katharine M; Hirst, Robert A; Chen, Cheng; Palazzo, Stefano G C; Emerenciana, Annette; Summers, Charlotte; Angyal, Adri; Porter, Linsey; Juss, Jatinder K; O'Callaghan, Christopher; Chilvers, Edwin R

2016-01-01

Background The inflamed bronchial mucosal surface is a profoundly hypoxic environment. Neutrophilic airway inflammation and neutrophil-derived proteases have been linked to disease progression in conditions such as COPD and cystic fibrosis, but the effects of hypoxia on potentially harmful neutrophil functional responses such as degranulation are unknown. Methods and results Following exposure to hypoxia (0.8% oxygen, 3 kPa for 4 h), neutrophils stimulated with inflammatory agonists (granulocyte-macrophage colony stimulating factor or platelet-activating factor and formylated peptide) displayed a markedly augmented (twofold to sixfold) release of azurophilic (neutrophil elastase, myeloperoxidase), specific (lactoferrin) and gelatinase (matrix metalloproteinase-9) granule contents. Neutrophil supernatants derived under hypoxic but not normoxic conditions induced extensive airway epithelial cell detachment and death, which was prevented by coincubation with the antiprotease α-1 antitrypsin; both normoxic and hypoxic supernatants impaired ciliary function. Surprisingly, the hypoxic upregulation of neutrophil degranulation was not dependent on hypoxia-inducible factor (HIF), nor was it fully reversed by inhibition of phospholipase C signalling. Hypoxia augmented the resting and cytokine-stimulated phosphorylation of AKT, and inhibition of phosphoinositide 3-kinase (PI3K)γ (but not other PI3K isoforms) prevented the hypoxic upregulation of neutrophil elastase release. Conclusion Hypoxia augments neutrophil degranulation and confers enhanced potential for damage to respiratory airway epithelial cells in a HIF-independent but PI3Kγ-dependent fashion. PMID:27581620

Pre- and post-operative values of serum CRP in patients undergoing surgery for brain tumour

International Nuclear Information System (INIS)

Syeda, T.; Rizvi, H.A.; Hashim, A.S.

2014-01-01

Objective: To determine the concentration of C-reactive protein in pre- and post-operative serum samples of brain tumour patients in order to detect the potential risks of post-operative infections. Methods: Serum C-reactive protein was measured on pre- and post-operative Day 1, Day 2 and Day 7 in 18 patients who underwent surgery for brain tumours. The study was performed at the Neurosurgical Ward, Jinnah Postgraduate Medical Centre, Karachi, from May 2007 to April 2008. Mean pre-operative patients and control values were compared using Mann-Whitney or Wilcoxon tests for comparing between pre- and post-operative values. P-value was considered significant at 5.0mg/L but no statistically significant difference was found when compared with healthy controls, with mean 4.4+-6.6 and 0.9+-0.7, respectively. Significantly raised serum concentrations were observed in all post-operative samples when compared with pre-operative samples. Serum CRP concentrations significantly increased post-operatively on Day 1, with mean value of 102.9+-82.0mg/L (p<0.0005), and further increased on Day 2 with mean value of 166.9+-128.1mg/L (p<0.0005), but declined on Day 7, with mean value of 42.7+-63.6mg/L (p<0.005). Conclusion: Pre-operative serum C-reactive protein concentrations of 28% of the patients were elevated, suggesting an association with brain tumours. Post-operative serum concentrations were significantly higher than those noted before the surgery. Absence of a fall of concentration from peak value on post-operative Day 2 or a secondary rise from post-operative Day 7 could be alarming for inter-current infection. (author)

Neutrophil extracellular traps promote deep vein thrombosis in mice

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Brill, A.; Fuchs, T.A.; Savchenko, A.S.; Thomas, G.M.; Martinod, K.; De Meyer, S.F.; Bhandari, A.A.; Wagner, D.D.

2011-01-01

Summary Background Upon activation, neutrophils can release nuclear material known as neutrophil extracellular traps (NETs), which were initially described as a part of antimicrobial defense. Extracellular chromatin was recently reported to be pro-thrombotic in vitro and to accumulate in plasma and thrombi of baboons with experimental deep vein thrombosis (DVT). Objective To explore the source and role of extracellular chromatin in DVT. Methods We used an established murine model of DVT induced by flow restriction (stenosis) in the inferior vena cava (IVC). Results We demonstrate that the levels of extracellular DNA increase in plasma after 6 h IVC stenosis, compared to sham-operated mice. Immunohistochemical staining revealed the presence of Gr-1-positive neutrophils in both red (RBC-rich) and white (platelet-rich) parts of thrombi. Citrullinated histone H3 (CitH3), an element of NETs’ structure, was present only in the red part of thrombi and was frequently associated with the Gr-1 antigen. Immunofluorescent staining of thrombi showed proximity of extracellular CitH3 and von Willebrand factor (VWF), a platelet adhesion molecule crucial for thrombus development in this model. Infusion of Deoxyribonuclease 1 (DNase 1) protected mice from DVT after 6 h and also 48 h IVC stenosis. Infusion of an unfractionated mixture of calf thymus histones increased plasma VWF and promoted DVT early after stenosis application. Conclusions Extracellular chromatin, likely originating from neutrophils, is a structural part of a venous thrombus and both the DNA scaffold and histones appear to contribute to the pathogenesis of DVT in mice. NETs may provide new targets for DVT drug development. PMID:22044575

The tripeptide feG regulates the production of intracellular reactive oxygen species by neutrophils

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Davison Joseph S

2006-06-01

Full Text Available Abstract Background The D-isomeric form of the tripeptide FEG (feG is a potent anti-inflammatory agent that suppresses type I hypersensitivity (IgE-mediated allergic reactions in several animal species. One of feG's primary actions is to inhibit leukocyte activation resulting in loss of their adhesive and migratory properties. Since activation of neutrophils is often associated with an increase in respiratory burst with the generation of reactive oxygen species (ROS, we examined the effect of feG on the respiratory burst in neutrophils of antigen-sensitized rats. A role for protein kinase C (PKC in the actions of feG was evaluated by using selective isoform inhibitors for PKC. Results At 18h after antigen (ovalbumin challenge of sensitized Sprague-Dawley rats a pronounced neutrophilia occurred; a response that was reduced in animals treated with feG (100 μg/kg. With antigen-challenged animals the protein kinase C (PKC activator, PMA, significantly increased intracellular ROS of circulating neutrophils, as determined by flow cytometry using the fluorescent probe dihydrorhodamine-123. This increase was prevented by treatment with feG at the time of antigen challenge. The inhibitor of PKCδ, rottlerin, which effectively prevented intracellular ROS production by circulating neutrophils of animals receiving a naïve antigen, failed to inhibit PMA-stimulated ROS production if the animals were challenged with antigen. feG treatment, however, re-established the inhibitory effects of the PKCδ inhibitor on intracellular ROS production. The extracellular release of superoxide anion, evaluated by measuring the oxidative reduction of cytochrome C, was neither modified by antigen challenge nor feG treatment. However, hispidin, an inhibitor of PKCβ, inhibited the release of superoxide anion from circulating leukocytes in all groups of animals. feG prevented the increased expression of the β1-integrin CD49d on the circulating neutrophils elicited by antigen

Neutrophilic dermatoses in a patient with collagenous colitis

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Didac Barco

2010-01-01

Full Text Available We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.

An oral Hemokine™, α-methylhydrocinnamate, enhances myeloid and neutrophil recovery following irradiation in vivo

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Faller, Douglas V.; Castaneda, Serguei A.; Zhou, Daohong; Vedamony, Merriline; Newburger, Peter E.; White, Gary L.; Kosanke, Stanley; Plett, P. Artur; Orschell, Christie M.; Boosalis, Michael S.; Perrine, Susan P.

2017-01-01

An oral therapeutic which reduces duration of cytopenias and is active following accidental radiation exposures is an unmet need in radiation countermeasures. Alpha methylhydrocinnamate (ST7) prolongs STAT-5 phosphorylation, reduces growth-factor dependency of multi-lineage cell lines, and stimulates erythropoiesis. Here, ST7 and its isomers were studied for their effects on myeloid progenitors and hematopoietic stem cells (HSCs) following radiation, in nonhuman primates, and murine irradiation models. Addition of ST7 or ST7-S increased CFU-GM production by 1.7-fold (p200/mm3 and neutropenia recovered in 6 days with ST7 treatment and 18 days in controls (p<0.05). In lethally-irradiated mice, marrow pathology at 15 days was hypocellular (10% cellularity) in controls, but normal (55–75% cellularity) with complete neutrophil maturation with ST7-S treatment. Following lethal irradiation, ST7, given orally for 4 days, reduced mortality, with 30% survival in ST7-animals vs 8% in controls, (p<0.05). Collectively, the studies indicate that ST7 and ST7-S enhance myeloid recovery post-radiation and merit further evaluation to accelerate hematologic recovery in conditions of radiation-related and other marrow hypoplasias. PMID:27888688

Potential role of recombinant secretory leucoprotease inhibitor in the prevention of neutrophil mediated matrix degradation.

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Llewellyn-Jones, C G; Lomas, D A; Stockley, R A

1994-06-01

Neutrophil elastase is able to degrade connective tissue matrices and is thought to be involved in the pathogenesis of destructive lung diseases. The ability of recombinant secretory leucoprotease inhibitor (rSLPI) to inhibit neutrophil mediated degradation of fibronectin in vitro is demonstrated and its efficacy compared with native alpha-1-proteinase inhibitor (n alpha 1-PI), recombinant alpha-1-proteinase inhibitor (r alpha 1-PI), and the chemical elastase inhibitor ICI 200,355. When preincubated with neutrophils both rSLPI and r alpha 1-PI were effective inhibitors of fibronectin degradation although n alpha 1-PI and ICI 200,355 were less effective. Recombinant SLPI was the most effective inhibitor when the cells were allowed to adhere to fibronectin before the addition of the inhibitors. Preincubation of rSLPI (0.1 mumol/l) with the fibronectin plate resulted in almost total inhibition of fibronectin degradation (reduced to 3.3 (SE 0.9)% of control). Pretreating the fibronectin plate with 1 mumol/l rSLPI, r alpha 1-PI and ICI 200,355 followed by thorough washing before the addition of cells resulted in no inhibition of fibronectin degradation with r alpha 1-PI and the ICI inhibitor, but rSLPI retained its inhibitory effect. This effect could be reduced by adding rSLPI in high pH buffer or 2 mol/1 NaCl. It is postulated that rSLPI binds to fibronectin to form a protective layer which prevents its degradation by neutrophil elastase. It may prove to be the most useful therapeutic agent in the prevention of neutrophil mediated lung damage.

Neutrophil adhesion and chemotaxis depend on substrate mechanics

International Nuclear Information System (INIS)

Jannat, Risat A; Hammer, Daniel A; Robbins, Gregory P; Ricart, Brendon G; Dembo, Micah

2010-01-01

Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K D of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against β 2 -integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

Neutrophil adhesion and chemotaxis depend on substrate mechanics

Energy Technology Data Exchange (ETDEWEB)

Jannat, Risat A; Hammer, Daniel A [Department of Bioengineering, University of Pennsylvania, 240 Skirkanich Hall, 210 South 33rd Street, Philadelphia, PA 19104 (United States); Robbins, Gregory P; Ricart, Brendon G [Department of Chemical and Biomolecular Engineering, University of Pennsylvania, 311A Towne Building, 220 South 33rd Street, Philadelphia, PA 19104 (United States); Dembo, Micah, E-mail: hammer@seas.upenn.ed [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States)

2010-05-19

Neutrophil adhesion to the vasculature and chemotaxis within tissues play critical roles in the inflammatory response to injury and pathogens. Unregulated neutrophil activity has been implicated in the progression of numerous chronic and acute diseases such as rheumatoid arthritis, asthma and sepsis. Cell migration of anchorage-dependent cells is known to depend on both chemical and mechanical interactions. Although neutrophil responses to chemical cues have been well characterized, little is known about the effect of underlying tissue mechanics on neutrophil adhesion and migration. To address this question, we quantified neutrophil migration and traction stresses on compliant hydrogel substrates with varying elasticity in a micromachined gradient chamber in which we could apply either a uniform concentration or a precise gradient of the bacterial chemoattractant fMLP. Neutrophils spread more extensively on substrates of greater stiffness. In addition, increasing the stiffness of the substrate leads to a significant increase in the chemotactic index for each fMLP gradient tested. As the substrate becomes stiffer, neutrophils generate higher traction forces without significant changes in cell speed. These forces are often displayed in pairs and focused in the uropod. Increases in the mean fMLP concentration beyond the K{sub D} of the receptor lead to a decrease in chemotactic index on all surfaces. Blocking with an antibody against {beta}{sub 2}-integrins leads to a significant reduction, but not an elimination, of directed motility on stiff materials, but no change in motility on soft materials, suggesting neutrophils can display both integrin-dependent and integrin-independent motility. These findings are critical for understanding how neutrophil migration may change in different mechanical environments in vivo and can be used to guide the design of migration inhibitors that more efficiently target inflammation.

A Neutrophil Proteomic Signature in Surgical Trauma Wounds

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Sander Bekeschus

2018-03-01

Full Text Available Non-healing wounds continue to be a clinical challenge for patients and medical staff. These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is therefore important to decipher molecular signatures that reflect the macroscopic process of wound healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy after surgical trauma to generate wound-derived protein profiles via global mass spectrometry. We confidently identified 311 proteins in exudates. Among them were expected targets belonging to the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200 post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine trioxidation to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually collected exudates, we confirmed presence of neutrophils and their products, such as microparticles and fragments containing myeloperoxidase and DNA. These data confirmed known and identified less known wound proteins and their PTMs, which may serve as resource for future studies on human wound healing.

Loss of neutrophil polarization in colon carcinoma liver metastases of mice with an inducible, liver-specific IGF-I deficiency.

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Rayes, Roni F; Milette, Simon; Fernandez, Maria Celia; Ham, Boram; Wang, Ni; Bourdeau, France; Perrino, Stephanie; Yakar, Shoshana; Brodt, Pnina

2018-03-20

The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls. However, unlike controls, these neutrophils did not acquire the (anti-inflammatory) tumor-promoting phenotype, as evidenced by retention of high ICAM-1 expression and nitric oxide production and low CXCR4, CCL5, and VEGF expression and arginase production, all characteristic of the (pro-inflammatory) phenotype. This coincided with an increase in apoptotic tumor cells and reduced metastasis. Neutrophils isolated from these mice also had reduced IGF-IR expression levels. These changes were not observed in iLID mice with a short-term (2 days) IGF-I depletion, despite a 70% reduction in their circulating IGF-I levels, indicating that a sustained IGF-I deficiency was necessary to alter the neutrophil phenotype. Similar results were obtained with the highly metastatic Lewis lung carcinoma subline H-59 cells and in mice injected with an IGF-Trap that blocks IGF-IR signaling by reducing ligand bioavailability. Our results implicate the IGF axis in neutrophil polarization and the induction of a pro-metastatic microenvironment in the liver.

Chemotactic Activity on Human Neutrophils to Streptococcus mutans

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Tetiana Haniastuti

2013-07-01

Full Text Available Objective: The aim of this study was to evaluate chemotactic activity o neutrophil to S. mutans. Chemotaxis assay was performed in blind well chambers. Materials and Methods: Hanks balanced salt solution (HBSS containing 106 S. mutans,  108 S. mutans, 10-8 M fMLP, or HBSS alone were placed in the lower wells of the chamber and covered with polycorbonate membrane filter. Neutrophils suspension (2x105 cells was then placed in the upper compartment. After incubation for 60 mins at 37ºC in a humidified atmosphere with 5% CO2, the filters were removed and stained with Giemsa. Result: ANOVA revealed statistically significant differences among groups (p<0.05, indicating that S. mutans induced neutrophils chemotaxis. The number of neutrophils migration in response to 108 S. mutans and 106 S. mutans were signifiantly greater compared to fMLP (p<0.05. Conclusion: S. mutans may activate human neutrophils, resulting in the chemotaxis of the neutrophils.DOI: 10.14693/jdi.v16i2.99

Effect of Isolation Techniques on Viability of Bovine Blood Neutrophils

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P. Sláma

2006-01-01

Full Text Available The effect of selected isolation methods on the viability of neutrophil granulocytes (neutrophils from the blood of healthy Holstein x Bohemian Red Pied crossbred heifers was evaluated. Two methods of neutrophil isolation were used: a neutrophil isolation on the basis of hypotonic erythrocyte lysis (in two variants: after the erythrocyte lysis proper, the cells were centrifuged at either 200 g or 1000 g, and b neutrophil isolation with FACS Lysing Solution as the lysing agent. The viability of the isolated neutrophils was evaluated on the basis of apoptosis and necrosis. The results obtained with flow cytometry (FCM suggest that, from the isolation techniques used, the method based on FACS Lysing Solution impaired the neutrophil viability least. After the application of this method, 5.36 ± 2.15% of neutrophils were apoptotic and 0.51 ± 0.12% were necrotic. In contrast, when the hypotonic erythrocyte lysis was used, the proportion of apoptotic neutrophils amounted to 42.14 ± 7.12% and 49.00 ± 14.70%, respectively, and 41.12 ± 5.55% and 36.91 ± 24.38% respectively of necrotic neutrophils (P < 0.01. This was also confirmed by the light microscopy. After the isolation with FASC Lysing Solution, 1.92 ± 1.74% of neutrophils were apoptotic and 1.05 ± 0.76% were necrotic, as distinct from after the hypotonic erythrocyte lysis where 9.43 ± 3.69% of neutrophils were apoptotic and 12.67 ± 4.74% of necrotic after centrifugation at 200 g, while 12.60 ± 4.35 were apoptotic and 14.96 ± 12.64% were necrotic after centrifugation at 1000 g. It follows from the above-mentioned data that hypotonic lysis is not a suitable method for the isolation of neutrophils, as the method itself markedly affects cell viability.

Prior inpatient admission increases the risk of post-operative infection in hepatobiliary and pancreatic surgery.

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Dong, Zachary M; Chidi, Alexis P; Goswami, Julie; Han, Katrina; Simmons, Richard L; Rosengart, Matthew R; Tsung, Allan

2015-12-01

Hepatobiliary and pancreatic (HPB) operations have a high incidence of post-operative nosocomial infections. The aim of the present study was to determine whether hospitalization up to 1 year before HPB surgery is associated with an increased risk of post-operative infection, surgical-site infection (SSI) and infection resistant to surgical chemoprophylaxis. A retrospective cohort study of patients undergoing HPB surgeries between January 2008 and June 2013 was conducted. A multivariable logistic regression model was used for controlling for potential confounders to determine the association between pre-operative admission and post-operative infection. Of the 1384 patients who met eligibility criteria, 127 (9.18%) experienced a post-operative infection. Pre-operative hospitalization was independently associated with an increased risk of a post-operative infection [adjusted odds ratio (aOR): 1.61, 95% confidence interval [CI]: 1.06-2.46] and SSI (aOR: 1.79, 95% CI: 1.07-2.97). Pre-operative hospitalization was also associated with an increased risk of post-operative infections resistant to standard pre-operative antibiotics (OR: 2.64, 95% CI: 1.06-6.59) and an increased risk of resistant SSIs (OR: 3.99, 95% CI: 1.25-12.73). Pre-operative hospitalization is associated with an increased incidence of post-operative infections, often with organisms that are resistant to surgical chemoprophylaxis. Patients hospitalized up to 1 year before HPB surgery may benefit from extended spectrum chemoprophylaxis. © 2015 International Hepato-Pancreato-Biliary Association.

The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

LENUS (Irish Health Repository)

Hayes, Elaine

2012-02-01

Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

The cystic fibrosis neutrophil: a specialized yet potentially defective cell.

LENUS (Irish Health Repository)

Hayes, Elaine

2011-04-01

Cystic fibrosis (CF) is one of the commonest genetically inherited diseases in the world. It is characterized by recurrent respiratory tract infections eventually leading to respiratory failure. One of the hallmarks of this disease is a persistent and predominantly neutrophil driven inflammation. Neutrophils provide the first line of defence by killing and digesting phagocytosed bacteria and fungi, yet despite advances in our understanding of the molecular and cellular basis of CF, there remains a paradox of why recruited CF neutrophils fail to eradicate bacterial infections in the lung. This review describes mechanisms involved in neutrophil migration, microbial killing and apoptosis leading to inflammatory resolution. We discuss dysregulated neutrophil activity and consider genetic versus inflammatory neutrophil reprogramming in CF and ultimately pharmacological modulation of the CF neutrophil for therapeutic intervention.

Different innate neutrophil responses in controlled and uncontrolled asthma

NARCIS (Netherlands)

Tang, Francesca; Foxley, Gloria; Gibson, Peter; Burgess, Janette; Baines, Katherine; Oliver, Brian

2015-01-01

Introduction: Respiratory viruses are a major cause of asthma exacerbations. Neutrophilic inflammation occurs during infections and is associated with difficult to treat asthma. The role of neutrophils in viral infections and whether neutrophil dysfunction contributes to exacerbation pathogenesis

A prospective randomized clinical study of the influence of primary closure or dressing on post-operative morbidity after mandibular third molar surgery

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Peter E Egbor

2014-01-01

Full Text Available Objective: The aim of the following study is to determine the effect of primary closure or dressing on post-operative morbidity after impacted lower third molar surgery. Materials and Methods: This was a randomized clinical study of 72 patients who had surgical extraction of impacted mandibular third molars. The subjects were divided into two groups of A and B. Group A had total closure (primary closure and Group B had whitehead varnish dressing of the socket. Pain, swelling and trismus were evaluated pre-operatively using visual analogue scale, flexible tape measuring method and inter-incisal distance measurement with Vernier Callipers respectively as well as post-operatively on 1 st , 2 nd , 3 rd , 5 th and 7 th day. Results: The study participants consisted of 27 males and 45 females in a ratio 1:1.7. With a mean age of 24.7 ± 4.9 years (range 19-33 years for Group A and 25.5 ± 4.3 years (range 20-39 years for Group B. Post-operative pain was not significantly affected by the closure techniques (P > 0.05. Dressing was found to significantly reduce the degree of swelling and trismus peaking on the 2 nd day (P = 0.0207 and P = 0.010 respectively. Conclusion: The use of dressing was more effective than primary closure to reduce the degree of swelling and trismus though its effect on post-operative pain reduction was not significant.

Sternal wound complications after primary isolated myocardial revascularization: the importance of the post-operative variables.

NARCIS (Netherlands)

Noyez, L.; Druten, J.A.M. van; Mulder, J.; Schroen, A.M.; Skotnicki, S.H.; Brouwer, R.

2001-01-01

OBJECTIVE: Select pre-, peri-, and post-operative variables, predictive for sternal wound complications (SWC), in a clinical setting. METHODS: We analyzed pre-, peri-, and post-operative data of 3815 patients who underwent a primary isolated bypass grafting. 100 patients (2.6%) had post-operative

Sphingosine kinase inhibition alleviates endothelial permeability induced by thrombin and activated neutrophils.

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Itagaki, Kiyoshi; Zhang, Qin; Hauser, Carl J

2010-04-01

Inflammation and microvascular thrombosis are interrelated causes of acute lung injury in the systemic inflammatory response syndrome. Neutrophils (polymorphonuclear neutrophil [PMN]) and endothelial cells (EC) activated by systemic inflammatory response syndrome interact to increase pulmonary vascular permeability, but the interactions between PMN and EC are difficult to study. Recently, we reported that sphingosine 1-phosphate is a second messenger eliciting store-operated calcium entry (SOCE) in response to inflammatory agonists in both PMN and EC. Store-operated calcium entry is therefore a target mechanism for the therapeutic modulation of inflammatory PMN-EC interactions. Here, we isolated, modeled, and studied the effects of pharmacologic SOCE inhibition using real-time systems to monitor EC permeability after exposure to activated PMN. We created systems to continuously assess permeability of human pulmonary artery endothelial cells and human microvascular endothelial cells from lung. Endothelial cells show increased permeability after challenge by activated PMN. Such permeability increases can be attenuated by exposure of the cocultures to sphingosine kinase (SK) inhibitors (SKI-2, N,N-dimethylsphingosine [DMS]) or Ca2+ entry inhibitors (Gd3+, MRS-1845). Human microvascular endothelial cells from lung pretreated with SKI-2 or DMS showed decreased permeability when later exposed to activated PMN. Likewise, when PMNs were activated with thapsigargin (TG) in the presence of SKI-2, DMS, Gd, or MRS-1845, their ability to cause EC permeability subsequently was reduced. SKI-2 also inhibited the activation of human pulmonary artery ECs by thrombin. These studies will provide a firm mechanistic foundation for understanding how systemic SOCE inhibition may be used to prevent acute lung injury in vivo.

Maintaining reduced noise levels in a resource-constrained neonatal intensive care unit by operant conditioning.

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Ramesh, A; Denzil, S B; Linda, R; Josephine, P K; Nagapoornima, M; Suman Rao, P N; Swarna Rekha, A

2013-03-01

To evaluate the efficacy of operant conditioning in sustaining reduced noise levels in the neonatal intensive care unit (NICU). Quasi-experimental study on quality of care. Level III NICU of a teaching hospital in south India. 26 staff employed in the NICU. (7 Doctors, 13 Nursing staff and 6 Nursing assistants). Operant conditioning of staff activity for 6 months. This method involves positive and negative reinforcement to condition the staff to modify noise generating activities. Comparing noise levels in decibel: A weighted [dB (A)] before conditioning with levels at 18 and 24 months after conditioning. Decibel: A weighted accounts for noise that is audible to human ears. Operant conditioning for 6 months sustains the reduced noise levels to within 62 dB in ventilator room 95% CI: 60.4 - 62.2 and isolation room (95% CI: 55.8 - 61.5). In the preterm room, noise can be maintained within 52 dB (95% CI: 50.8 - 52.6). This effect is statistically significant in all the rooms at 18 months (P = 0.001). At 24 months post conditioning there is a significant rebound of noise levels by 8.6, 6.7 and 9.9 dB in the ventilator, isolation and preterm room, respectively (P =0.001). Operant conditioning for 6 months was effective in sustaining reduced noise levels. At 18 months post conditioning, the noise levels were maintained within 62 dB (A), 60 dB (A) and 52 dB (A) in the ventilator, isolation and pre-term room, respectively. Conditioning needs to be repeated at 12 months in the ventilator room and at 18 months in the other rooms.

Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death

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Hiroto Kambara

2018-03-01

Full Text Available Summary: Gasdermin D (GSDMD is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in macrophages, in which activated inflammatory caspases cleave GSDMD to produce an N-terminal fragment (GSDMD-cNT to trigger pyroptosis, GSDMD cleavage and activation in neutrophils was caspase independent. It was mediated by a neutrophil-specific serine protease, neutrophil elastase (ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. ELANE-mediated GSDMD cleavage was upstream of the caspase cleavage site and produced a fully active ELANE-derived NT fragment (GSDMD-eNT that induced lytic cell death as efficiently as GSDMD-cNT. Thus, GSDMD is pleiotropic, exerting both pro- and anti-inflammatory effects that make it a potential target for antibacterial and anti-inflammatory therapies. : Kambara et al. find that GSDMD deficiency augments host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, establishing GSDMD as a negative regulator of innate immunity. GSDMD cleavage and activation in neutrophils is mediated by ELANE, released from cytoplasmic granules into the cytosol in aging neutrophils. Keywords: GSDMD, neutrophil death, neutrophil elastase, innate immunity, host defense

Effects of Porphyromonas gingivalis LipopolysaccharideTolerized Monocytes on Inflammatory Responses in Neutrophils.

Directory of Open Access Journals (Sweden)

Xiang-Qing Zhu

Full Text Available Periodontitis is a chronic inflammatory disease induced by bacteria. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, which is termed endotoxin tolerance. The role and mechanism of lipopolysaccharide (LPS-tolerized monocytes in inflammatory responses in neutrophils are currently unclear. Here, conditioned supernatants were collected from THP-1 cells treated with or without repeated 1 μg/ml Porphyromonas gingivalis (P.gingivalis LPS. The chemotactic response of freshly isolated neutrophils recruited by supernatants was determined by a transwell migration assay, which demonstrated a reduced migration of neutrophils stimulated with supernatants from tolerized THP-1 cells in comparison to non-tolerized THP-1 cells. In addition, there was a marked increase in reactive oxygen species (ROS generation and a significant decrease in Caspase 3 activities in neutrophils treated with supernatants from THP-1 cells that were treated repeatedly with P.gingivalis LPS in comparison to single treatment. A cytokine antibody array was then used to assess cytokine expression patterns in THP-1 cells. In tolerized THP-1 cells, 43 cytokine (43/170 expression levels were decreased, including chemokine ligand 23 (CCL23 and IFN-γ, while 11 cytokine (11/170 expression levels were increased, such as death receptor 6 (DR6. Furthermore, there was decreased production of IFN-γ and epithelial neutrophil activating peptide-78 (ENA-78 in THP-1 cells after stimulation with repeated P. gingivalis LPS in comparison to single challenge, which was confirmed by ELISA. Therefore, P.gingivalis LPS- tolerized THP-1 cells were able to depress neutrophil chemotaxis and apoptosis, and contribute to respiratory burst, which might be related to the changes in cytokine expression patterns in THP-1 cells.

Neutrophils, a candidate biomarker and target for radiation therapy?

Science.gov (United States)

Schernberg, Antoine; Blanchard, Pierre; Chargari, Cyrus; Deutsch, Eric

2017-11-01

Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype. This supports

Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment

Directory of Open Access Journals (Sweden)

Jaehong Kim

2016-01-01

Full Text Available Distinct tumor microenvironment forms in each progression step of cancer and has diverse capacities to induce both adverse and beneficial consequences for tumorigenesis. It is now known that immune cells can be activated to favor tumor growth and progression, most probably influenced by the tumor microenvironment. Tumor-associated macrophages and tumor-associated neutrophils can exert protumoral functions, enhancing tumor cell invasion and metastasis, angiogenesis, and extracellular matrix remodeling, while inhibiting the antitumoral immune surveillance. Considering that neutrophils in inflammatory environments recruit macrophages and that recruited macrophages affect neutrophil functions, there may be various degrees of interaction between tumor-associated macrophages and tumor-associated neutrophils. Platelets also play an important role in the recruitment and regulation of monocytic and granulocytic cells in the tumor tissues, suggesting that platelet function may be essential for generation of tumor-associated macrophages and tumor-associated neutrophils. In this review, we will explore the biology of tumor-associated macrophages and tumor-associated neutrophils and their possible interactions in the tumor microenvironment. Special attention will be given to the recruitment and activation of these tumor-associated cells and to the roles they play in maintenance of the tumor microenvironment and progression of tumors.

Granule protein processing and regulated secretion in neutrophils

Directory of Open Access Journals (Sweden)

Avinash eSheshechalam

2014-09-01

Full Text Available Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

Pre-operative and early post-operative factors associated with surgical site infection after laparoscopic sleeve gastrectomy.

Science.gov (United States)

Ruiz-Tovar, Jaime; Oller, Inmaculada; Llavero, Carolina; Arroyo, Antonio; Muñoz, Jose Luis; Calero, Alicia; Diez, María; Zubiaga, Lorea; Calpena, Rafael

2013-08-01

Surgical procedures on obese patients are expected to have a high incidence of surgical site infection (SSI). The identification of pre-operative or early post-operative risk factors for SSI may help the surgeon to identify subjects in risk and adequately optimize their status. We conducted a study of the association of comorbidities and pre- and post-operative analytical variables with SSI following laparoscopic sleeve gastrectomy for the treatment of morbid obesity. We performed a prospective study of all morbidly obese patients undergoing laparoscopic sleeve gastrectomy as a bariatric procedure between 2007 and 2011. An association of clinical and analytical variables with SSI was investigated. The study included 40 patients with a mean pre-operative body mass index (BMI) of 51.2±7.9 kg/m(2). Surgical site infections appeared in three patients (7.5%), of whom two had an intra-abdominal abscess located in the left hypochondrium and the third had a superficial incisional SSI. Pre-operatively, a BMI >45 kg/m(2) (OR 8.7; p=0.008), restrictive disorders identified by pulmonary function tests (OR 10.0; p=0.012), a serum total protein concentration 30 mcg/dL (OR 13.0; p=0.003), and a mean corpuscular volume (MCV) operative SSI. Post-operatively, a serum glucose >128 mg/dL (OR 4.7; p=0.012) and hemoglobin operative anemia and hyperglycemia as risk factors for SSI. In these situations, the surgeon must be aware of and seek to control these risk factors.

Swell activated chloride channel function in human neutrophils

Energy Technology Data Exchange (ETDEWEB)

Salmon, Michael D. [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom); Ahluwalia, Jatinder, E-mail: j.ahluwalia@uel.ac.uk [Leukocyte and Ion Channel Research Laboratory, School of Health and Biosciences, University of East London, Stratford Campus, London E15 4LZ (United Kingdom)

2009-04-17

Non-excitable cells such as neutrophil granulocytes are the archetypal inflammatory immune cell involved in critical functions of the innate immune system. The electron current generated (I{sub e}) by the neutrophil NADPH oxidase is electrogenic and rapidly depolarises the membrane potential. For continuous function of the NADPH oxidase, I{sub e} has to be balanced to preserve electroneutrality, if not; sufficient depolarisation would prevent electrons from leaving the cell and neutrophil function would be abrogated. Subsequently, the depolarisation generated by the neutrophil NADPH oxidase I{sub e} must be counteracted by ion transport. The finding that depolarisation required counter-ions to compensate electron transport was followed by the observation that chloride channels activated by swell can counteract the NADPH oxidase membrane depolarisation. In this mini review, we discuss the research findings that revealed the essential role of swell activated chloride channels in human neutrophil function.

Effect of moderate exercise on peritoneal neutrophils from juvenile rats.

Science.gov (United States)

Braz, Glauber Ruda; Ferreira, Diorginis Soares; Pedroza, Anderson Apolonio; da Silva, Aline Isabel; Sousa, Shirley Maria; Pithon-Curi, Tania Cristina; Lagranha, Claudia

2015-09-01

Previous studies showed that moderate exercise in adult rats enhances neutrophil function, although no studies were performed in juvenile rats. We evaluated the effects of moderate exercise on the neutrophil function in juvenile rats. Viability and neutrophils function were evaluated. Moderate exercise did not impair the viability and mitochondrial transmembrane potential of neutrophils, whereas there was greater reactive oxygen species production (164%; p < 0.001) and phagocytic capacity (29%; p < 0.05). Our results suggest that moderate exercise in juvenile rats improves neutrophil function, similar to adults.

D-lactic acid interferes with the effects of platelet activating factor on bovine neutrophils.

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Alarcón, P; Conejeros, I; Carretta, M D; Concha, C; Jara, E; Tadich, N; Hidalgo, M A; Burgos, R A

2011-11-15

D-lactic acidosis occurs in ruminants, such as cattle, with acute ruminal acidosis caused by ingestion of excessive amounts of highly fermentable carbohydrates. Affected animals show clinical signs similar to those of septic shock, as well as acute laminitis and liver abscesses. It has been proposed that the inflammatory response and susceptibility to infection could both be caused by the inhibition of phagocytic mechanisms. To determine the effects of d-lactic acid on bovine neutrophil functions, we pretreated cells with different concentrations of D-lactic acid and measured intracellular pH using 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM) and calcium flux using FLUO-3 AM-loaded neutrophils. Reactive oxygen species (ROS) production was measured using a luminol chemiluminescence assay, and MMP-9/gelatinase-B granule release was measured by zymography. CD11b and CD62L/l-selectin expression, changes in cell shape, superoxide anion production, phagocytosis of Escherichia coli-Texas red bioparticles, and apoptosis were all measured using flow cytometry. Our results demonstrated that D-lactic acid reduced ROS production, CD11b upregulation and MMP-9 release in bovine neutrophils treated with 100 nM platelet-activating factor (PAF). D-lactic acid induced MMP-9 release and, at higher concentrations, upregulated CD11b expression, decrease L-selectin expression, and induces late apoptosis. We concluded that D-lactic acid can interfere with neutrophil functions induced by PAF, leading to reduced innate immune responses during bacterial infections. Moreover, the increase of MMP-9 release and CD11b expression induced by 10mM D-lactic acid could promote an nonspecific neutrophil-dependent inflammatory reaction in cattle with acute ruminal acidosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Intravenous analgesics for pain management in post- operative ...

African Journals Online (AJOL)

Intravenous analgesics for pain management in post- operative patients: a comparative study of their efficacy and adverse ... patient anxiety, stress, and dissatisfaction. Adequate ... genders who were scheduled to undergo abdominal surgery (hemicolectomy, exploratory ... analysis (n = 48) and separated into three groups.

Low degree of satisfactory individual pain relief in post-operative pain trials.

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Geisler, A; Dahl, J B; Karlsen, A P H; Persson, E; Mathiesen, O

2017-01-01

The majority of clinical trials regarding post-operative pain treatment focuses on the average analgesic efficacy, rather than on efficacy in individual patients. It has been argued, that in acute pain trials, the underlying distributions are often skewed, which makes the average unfit as the only way to measure efficacy. Consequently, dichotomised, individual responder analyses using a predefined 'favourable' response, e.g. Visual Analogue Scale (VAS) pain scores ≤ 30, have recently been suggested as a more clinical relevant outcome. We re-analysed data from 16 randomised controlled trials of post-operative pain treatment and from meta-analyses of a systematic review regarding hip arthroplasty. The predefined success criterion was that at least 80% of patients in active treatment groups should obtain VAS < 30 at 6 and 24 h post-operatively. In the analysis of data from the randomised controlled trials, we found that at 6 h post-operatively, 50% (95% CI: 31-69) of patients allocated to active treatment reached the success criterion for pain at rest and 14% (95% CI: 5-34) for pain during mobilisation. At 24 h post-operatively, 60% (95% CI: 38-78) of patients allocated to active treatment reached the success criterion for pain at rest, and 15% (95% CI: 5-36) for pain during mobilisation. Similar results were found for trials from the meta-analyses. Our results indicate that for conventional, explanatory trials of post-operative pain, individual patient's achievement of a favourable response to analgesic treatment is rather low. Future pragmatic clinical trials should focus on both average pain levels and individual responder analyses in order to promote effective pain treatment at the individually patient level. © 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Demodex-associated bacterial proteins induce neutrophil activation.

LENUS (Irish Health Repository)

2012-02-01

Background: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea thus suggesting a possible role for bacterial proteins in the etiology of this condition. Objectives: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. Methods: Bacterial cells were lysed and proteins were partially purified by AKTA-FPLC. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. Results: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of MMP-9, an enzyme known to degrade collagen and cathelicidin, an antimicrobial peptide. In addition neutrophils exposed to the bacterial proteins demonstrated elevated rates of Il-8 and TNF-alpha production. Conclusions: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.

Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ injury in rats.

Directory of Open Access Journals (Sweden)

Tsong-Long Hwang

Full Text Available Neutrophil activation is associated with the development of organ injury after trauma-hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma-hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma-hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma-hemorrhagic shock-induced organ injury in rats.

Impact of neutrophil-secreted myeloid related proteins 8 and 14 (MRP 8/14) on leishmaniasis progression.

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Contreras, Irazú; Shio, Marina T; Cesaro, Annabelle; Tessier, Philippe A; Olivier, Martin

2013-01-01

The myeloid-related proteins (MRPs) 8/14 are small proteins mainly produced by neutrophils, which have been reported to induce NO production in macrophages. On the other hand, Leishmania survives and multiplies within phagocytes by inactivating several of their microbicidal functions. Whereas MRPs are rapidly released during the innate immune response, their role in the regulation of Leishmaniasis is still unknown. In vitro experiments revealed that Leishmania infection alters MRP-induced signaling, leading to inhibition of macrophage functions (NO, TNF-α). In contrast, MRP-primed cells showed normal signaling activation and NO production in response to Leishmania infection. Using a murine air-pouch model, we observed that infection with L. major induced leukocyte recruitment and MRP secretion comparable to LPS-treated mice. Depletion of MRPs significantly reduced these inflammatory events and augmented both parasite load and footpad swelling during the first 8 weeks post-infection, as also observed in MRP KO mice. On the contrary, mouse treatment with recombinant MRPs (rMRPs) had the opposite effect. Collectively, our results suggest that rapid secretion of MRPs by neutrophils at the site of infection may protect uninfected macrophages and favor a more efficient innate inflammatory response against Leishmania infection. In summary, our study reveals the critical role played by MRPs in the regulation of Leishmania infection and how this pathogen can subvert its action.

Post-Operative Infection Is an Independent Risk Factor for Worse Long-Term Survival after Colorectal Cancer Surgery.

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Kerin Povšič, Milena; Ihan, Alojz; Beovič, Bojana

2016-12-01

Colorectal cancer surgery is associated with a high incidence of post-operative infections, the outcome of which may be improved if diagnosed and treated early enough. We compared white blood cell (WBC) count, C-reactive protein (CRP), and procalcitonin (PCT) as predictors of post-operative infections and analyzed their impact on long-term survival. This retrospective study included 186 patients undergoing colorectal surgery. Post-operative values of WBC, CRP, and PCT were analyzed by the receiver operating characteristic (ROC) analysis. We followed infections 30 d after the surgery. A five-year survival was analyzed by Kaplan-Meier method and prognostic factors by Cox regression model. Fifty-five patients (29.5%) developed post-operative infection, the most frequent of which was surgical site infection (SSI). C-reactive protein on post-operative day three and PCT on post-operative day two demonstrated the highest diagnostic accuracy for infection (area under the curve [AUC] 0.739 and 0.735). C-reactive protein on post-operative day three was an independent predictor of infection. Five-year survival was higher in the non-infected group (70.8%), compared with the infected group (52.1%). The worst survival (40.9%) was identified in patients with organ/space SSI. Post-operative infection and tumor stage III-IV were independent predictors of a worse five-year survival. C-reactive protein on post-operative day three and PCT on post-operative day two may be early predictors of infection after colorectal cancer surgery. Post-operative infections in particular organ/space SSI have a negative impact on long-term survival.

Taurine modulates neutrophil function but potentiates uropathogenic E. coli infection in the murine bladder.

LENUS (Irish Health Repository)

Condron, Claire

2010-08-01

Eradication of a urinary tract infection (UTI) appears to be related to a number of innate host defence mechanisms and their interactions with invading bacteria. Recurrent UTIs (rUTIs) pose a difficult problem in that these bacteria use both host and bacterial factors to evade elimination. Neutrophil bactericidal function is depressed, both systemically and in urine, in patients with a history of recurrent UTI. Taurine is a semi-essential amino acid and is successful in preserving neutrophil bactericidal function in urine. Taurine may preserve neutrophil function at the urothelium and thus aid UTI resolution. Adult female (6 weeks old) C57Bl\\/6 mice were randomised into three groups: a saline gavage only control group, a saline gavage + E. coli group, and a taurine gavage + E. coli group [21 g\\/70 kg taurine in 0.9% normal saline (N\\/S) for 5 days]. Whilst taurine gavage pre-treatment resulted in increased serum neutrophils respiratory burst activity, at the urothelial-endothelial interface it caused higher colony forming units in the urine and a higher incidence of E. coli invasion in the bladder wall with no evidence of increased bladder wall neutrophils infiltration on MPO assay of histological assessment. Histologically there was also evidence of reduced bladder inflammation and urothelial cell apoptosis. In conclusion, taurine effectively increases neutrophils activity but given its anti-inflammatory properties, at the expense of decreased urothelial-endothelial activation thus preventing clearance of active E. coli infection in the bladder. Despite the negative results, this study demonstrates the importance of modulating interactions at the urothelial interface.

Neutrophils, dendritic cells and Toxoplasma.

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Denkers, Eric Y; Butcher, Barbara A; Del Rio, Laura; Bennouna, Soumaya

2004-03-09

Toxoplasma gondii rapidly elicits strong Type 1 cytokine-based immunity. The necessity for this response is well illustrated by the example of IFN-gamma and IL-12 gene knockout mice that rapidly succumb to the effects of acute infection. The parasite itself is skilled at sparking complex interactions in the innate immune system that lead to protective immunity. Neutrophils are one of the first cell types to arrive at the site of infection, and the cells release several proinflammatory cytokines and chemokines in response to Toxoplasma. Dendritic cells are an important source of IL-12 during infection with T. gondii and other microbial pathogens, and they are also specialized for high-level antigen presentation to T lymphocytes. Tachyzoites express at least two types of molecules that trigger innate immune cell cytokine production. One of these involves Toll-like receptor/MyD88 pathways common to many microbial pathogens. The second pathway is less conventional and involves molecular mimicry between a parasite cyclophilin and host CC chemokine receptor 5-binding ligands. Neutrophils, dendritic cells and Toxoplasma work together to elicit the immune response required for host survival. Cytokine and chemokine cross-talk between parasite-triggered neutrophils and dendritic cells results in recruitment, maturation and activation of the latter. Neutrophil-empowered dendritic cells possess properties expected of highly potent antigen presenting cells that drive T helper 1 generation.

A stable aspirin-triggered lipoxin A4 analog blocks phosphorylation of leukocyte-specific protein 1 in human neutrophils.

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Ohira, Taisuke; Bannenberg, Gerard; Arita, Makoto; Takahashi, Minoru; Ge, Qingyuan; Van Dyke, Thomas E; Stahl, Gregory L; Serhan, Charles N; Badwey, John A

2004-08-01

Lipoxins and their aspirin-triggered 15-epimers are endogenous anti-inflammatory agents that block neutrophil chemotaxis in vitro and inhibit neutrophil influx in several models of acute inflammation. In this study, we examined the effects of 15-epi-16-(p-fluoro)-phenoxy-lipoxin A(4) methyl ester, an aspirin-triggered lipoxin A(4)-stable analog (ATLa), on the protein phosphorylation pattern of human neutrophils. Neutrophils stimulated with the chemoattractant fMLP were found to exhibit intense phosphorylation of a 55-kDa protein that was blocked by ATLa (10-50 nM). This 55-kDa protein was identified as leukocyte-specific protein 1, a downstream component of the p38-MAPK cascade in neutrophils, by mass spectrometry, Western blotting, and immunoprecipitation experiments. ATLa (50 nM) also reduced phosphorylation/activation of several components of the p38-MAPK pathway in these cells (MAPK kinase 3/MAPK kinase 6, p38-MAPK, MAPK-activated protein kinase-2). These results indicate that ATLa exerts its anti-inflammatory effects, at least in part, by blocking activation of the p38-MAPK cascade in neutrophils, which is known to promote chemotaxis and other proinflammatory responses by these cells.

Neutrophil heterogeneity: implications for homeostasis and pathogenesis

NARCIS (Netherlands)

Silvestre-Roig, Carlos; Hidalgo, Andres; Soehnlein, Oliver

2016-01-01

Neutrophils are polymorphonuclear leukocytes of the phagocytic system that act as first line of host defense against invading pathogens but are also important mediators of inflammation-induced injury. In contrast to other members of the innate immune system, neutrophils are classically considered a

Effects of tramadol or morphine in dogs undergoing castration on intra-operative electroencephalogram responses and post-operative pain.

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Kongara, K; Chambers, J P; Johnson, C B; Dukkipati, V S R

2013-11-01

To compare the effects of pre-operatively administered tramadol with those of morphine on electroencephalographic responses to surgery and post-operative pain in dogs undergoing castration. Dogs undergoing castration were treated with either pre-operative morphine (0.5 mg/kg S/C, n = 8) or tramadol (3 mg/kg S/C, n = 8). All dogs also received 0.05 mg/kg acepromazine and 0.04 mg/kg atropine S/C in addition to the test analgesic. Anaesthesia was induced with thiopentone administered I/V to effect and maintained with halothane in oxygen. Respiratory rate, heart rate, end-tidal halothane tension (EtHal) and end-tidal CO2 tension (EtCO2) were monitored throughout surgery. Electroencephalograms (EEG) were recorded continuously using a three electrode montage. Median frequency (F50), total power (Ptot) and 95% spectral edge frequency (F95) derived from EEG power spectra recorded before skin incision (baseline) were compared with those recorded during ligation of the spermatic cords of both testicles. Post-operatively, pain was assessed after 1, 3, 6 and 9 h using the short form of the Glasgow composite measure pain scale (CMPS-SF). Dogs premedicated with tramadol had higher mean F50 (12.2 (SD 0.2) Hz) and lower Ptot (130.39 (SD 12.1) µv(2)) compared with those premedicated with morphine (11.5 (SD 0.2) Hz and 161.8 (SD 15.1) µv(2), respectively; p0.05). The F95 of the EEG did not differ between the two groups during the ligation of either testicle (p > 0.05). Post-operatively, no significant differences in the CMPS-SF score were found between animals premedicated with tramadol and morphine at any time during the post-operative period. No dog required rescue analgesia. Tramadol and morphine administered pre-operatively provided a similar degree of post-operative analgesia in male dogs at the doses tested.

Neutrophils in Homeostasis, Immunity, and Cancer.

Science.gov (United States)

Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

2017-01-17

Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutrophilic dermatoses in a patient with collagenous colitis

OpenAIRE

Didac Barco; Maria A. Barnadas; Esther Roé; Francisco J. Sancho; Elena Ricart; Agustín Alomar

2010-01-01

We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate...

Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

Science.gov (United States)

Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

2013-08-01

Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

Post-operative delirium is an independent predictor of 30-day hospital readmission after spine surgery in the elderly (≥65years old): A study of 453 consecutive elderly spine surgery patients.

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Elsamadicy, Aladine A; Wang, Timothy Y; Back, Adam G; Lydon, Emily; Reddy, Gireesh B; Karikari, Isaac O; Gottfried, Oren N

2017-07-01

In the last decade, costs of U.S. healthcare expenditures have been soaring, with billions of dollars spent on hospital readmissions. Identifying causes and risk factors can reduce soaring readmission rates and help lower healthcare costs. The aim of this is to determine if post-operative delirium in the elderly is an independent risk factor for 30-day hospital readmission after spine surgery. The medical records of 453 consecutive elderly (≥65years old) patients undergoing spine surgery at Duke University Medical Center from 2008 to 2010 were reviewed. We identified 17 (3.75%) patients who experienced post-operative delirium according to DSM-V criteria. Patient demographics, comorbidities, and post-operative complication rates were collected for each patient. Elderly patients experiencing post-operative delirium had an increased length of hospital stay (10.47days vs. 5.70days, p=0.009). Complication rates were similar between the cohorts with the post-operative delirium patients having increased UTI and superficial surgical site infections. In total, 12.14% of patients were re-admitted within 30-days of discharge, with post-operative delirium patients experiencing approximately a 4-fold increase in 30-day readmission rates (Delirium: 41.18% vs. No Delirium: 11.01%, p=0.002). In a multivariate logistic regression analysis, post-operative delirium is an independent predictor of 30-day readmission after spine surgery in the elderly (p=0.03). Elderly patients experiencing post-operative delirium after spine surgery is an independent risk factor for unplanned readmission within 30-days of discharge. Preventable measures and early awareness of post-operative delirium in the elderly may help reduce readmission rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of manual acupuncture on blood neutrophil counts in moderate intensity exercise

Science.gov (United States)

Ciang, C. Y.; Simadibrata, C.; Tobing, A.; Srilestari, A.

2017-08-01

Exercise, even though it has a beneficial effect, can cause muscle damage and trigger inflammatory responses, as evidenced by increased neutrophils in the blood. Acupuncture is a therapeutic modality that is expected to reduce acute inflammatory responses due to exercise. Thirty untrained men were divided randomly into two groups. The manual acupuncture group (n = 15) received stimulation at acupoints ST36 and SP6 bilateral by needle insertion, while the placebo group (n = 15) received insertion of needles on plaster without penetrating the skin. Therapy was done once for 30 minutes immediately after the subjects completed the exercise. Blood neutrophil counts were assessed before exercise and one hour after exercise ended. The results show there is a statistically significant difference in the number of neutrophils before and after exercise between the manual acupuncture group and the placebo group (0.08±0.91 and 0.97±0.70 p = 0.006). Acupuncture therapy effectively mitigates the acute inflammatory response triggered by exercise.

Neutrophil Leukocyte: Combustive Microbicidal Action and Chemiluminescence

Directory of Open Access Journals (Sweden)

Robert C. Allen

2015-01-01

Full Text Available Neutrophil leukocytes protect against a varied and complex array of microbes by providing microbicidal action that is simple, potent, and focused. Neutrophils provide such action via redox reactions that change the frontier orbitals of oxygen (O2 facilitating combustion. The spin conservation rules define the symmetry barrier that prevents direct reaction of diradical O2 with nonradical molecules, explaining why combustion is not spontaneous. In burning, the spin barrier is overcome when energy causes homolytic bond cleavage producing radicals capable of reacting with diradical O2 to yield oxygenated radical products that further participate in reactive propagation. Neutrophil mediated combustion is by a different pathway. Changing the spin quantum state of O2 removes the symmetry restriction to reaction. Electronically excited singlet molecular oxygen (O2*1 is a potent electrophilic reactant with a finite lifetime that restricts its radius of reactivity and focuses combustive action on the target microbe. The resulting exergonic dioxygenation reactions produce electronically excited carbonyls that relax by light emission, that is, chemiluminescence. This overview of neutrophil combustive microbicidal action takes the perspectives of spin conservation and bosonic-fermionic frontier orbital considerations. The necessary principles of particle physics and quantum mechanics are developed and integrated into a fundamental explanation of neutrophil microbicidal metabolism.

Potentially pathogenic airway bacteria and neutrophilic inflammation in treatment resistant severe asthma.

Science.gov (United States)

Green, Benjamin J; Wiriyachaiporn, Surasa; Grainge, Christopher; Rogers, Geraint B; Kehagia, Valia; Lau, Laurie; Carroll, Mary P; Bruce, Kenneth D; Howarth, Peter H

2014-01-01

Molecular microbiological analysis of airway samples in asthma has demonstrated an altered microbiome in comparison to healthy controls. Such changes may have relevance to treatment-resistant severe asthma, particularly those with neutrophilic airway inflammation, as bacteria might be anticipated to activate the innate immune response, a process that is poorly steroid responsive. An understanding of the relationship between airway bacterial presence and dominance in severe asthma may help direct alternative treatment approaches. We aimed to use a culture independent analysis strategy to describe the presence, dominance and abundance of bacterial taxa in induced sputum from treatment resistant severe asthmatics and correlate findings with clinical characteristics and airway inflammatory markers. Induced sputum was obtained from 28 stable treatment-resistant severe asthmatics. The samples were divided for supernatant IL-8 measurement, cytospin preparation for differential cell count and Terminal Restriction Fragment Length Polymorphism (T-RFLP) profiling for bacterial community analysis. In 17/28 patients, the dominant species within the airway bacterial community was Moraxella catarrhalis or a member of the Haemophilus or Streptococcus genera. Colonisation with these species was associated with longer asthma disease duration (mean (SD) 31.8 years (16.7) vs 15.6 years (8.0), p = 0.008), worse post-bronchodilator percent predicted FEV1 (68.0% (24.0) vs 85.5% (19.7), p = 0.025) and higher sputum neutrophil differential cell counts (median (IQR) 80% (67-83) vs 43% (29-67), p = 0.001). Total abundance of these organisms significantly and positively correlated with sputum IL-8 concentration and neutrophil count. Airway colonisation with potentially pathogenic micro-organisms in asthma is associated with more severe airways obstruction and neutrophilic airway inflammation. This altered colonisation may have a role in the development of an asthma phenotype that

Estimation of efficiency of new local rehabilitation method at the early post-operative period after dental implantation

Directory of Open Access Journals (Sweden)

A. V. Pasechnik

2017-01-01

  Summary Despite of success of dental implantation, there are often complications at the early post-operative period of implant placing associated with wound damage and aseptic inflammation. Purpose of the work is studying clinical efficiency of combined local application of new mucosal gel “Apior” and magnetotherapy at the early post-operative period after dental implantation. Combined local application of the mucosal gel “Apior” and pulsating low-frequency electromagnetic field in the complex medical treatment of patients after conducting an operation of setting dental implants favourably affects the common state of patients and clinical symptoms of inflammation in the area of operating wound. As compared with patients who had traditional anti-inflammatory therapy, the patients treated with local application of apigel and magnetoterapy had decline of edema incidence, of gingival mucosa hyperemia, of discomfort in the area of conducted operation. There occurred more rapid improvement of inflammation painfulness, which correlated with the improvement of hygienic state of oral cavity and promoted to prevention of bacterial content of damaged mucous surfaces. Estimation of microvasculatory blood stream by the method of ultrasonic doppler flowmetry revealed more rapid normalization of volume and linear high systole speed of blood stream in the periimplant tissues in case of use of new complex local rehabilitation method, that testified to the less pronounced inflammation of oral mucosa after the operation. The authors came to conclusion that the local application of the offered method of medical treatment of early post-operative complications of dental implantation reduces terms of renewal of structural-functional integrity of oral mucosa, helps in preventing development of inflammatory complications and strengthening endosseus implant. The inclusion in the treatment management of a new combined method of application of mucosal gel “Apior” and

Evaluation of Post-Operative Antibiotic Administration on Phenotypic ...

African Journals Online (AJOL)

But baseline data to judge effects of long-term post-operative antibiotic administration in clinical and surgical canine health conditions are currently lacking in Nigeria. This study aimed at providing vital baseline antibiotic profiles of canine bacteria of veterinary and public health importance. Phenotypic antibiotic susceptibility ...

Differential effector responses by circulating/blood and tissue/peritoneal neutrophils following burn combined with Enterococcus faecalis infection.

Science.gov (United States)

Fazal, Nadeem; Shelip, Alla; Siddiqui, Erum; Ali, Ashraf; Azim, Anser C; Al-Ghoul, Walid M

2012-03-01

Recently we found that superimposition of Enterococcus faecalis infection on burn injury caused an eruption of host mortality not seen with either individual challenge. We hypothesized that the Enterococcus bacteria, and/or factors related to these organisms, aggravate burn-induced modulations in host defense by neutrophils. Our study focuses on alterations in neutrophils' oxidative, proteolytic, and adhesive functions and transendothelial migration of neutrophils in burn rats inoculated with E. faecalis. Rats were subjected to burn (30% total body surface area) and then intra-abdominally inoculated with E. faecalis (10(4)CFU kg(-1) b.w). Polymorphonuclear neutrophils (PMNs) were harvested from circulating/blood and tissue/peritoneal cavity at day-2 post injury. Extracellular release of O(-)(2) anion production was determined by luminometry, and intracellular production of reactive oxygen species was measured by digital imaging technique. Fluoroscan analysis and confocal microscopy determined intracellular elastase production. The expression of adhesion molecule CD11b/CD18 was performed by flow cytometry. Calcein AM-labeled PMNs were co-cultured with TNF-α-stimulated rat lung microvascular endothelial cells, and their ability to adhere was assessed by fluorometry and digital imaging and finally, chemotaxis was measured by neutrophil transmigration assays. The results showed differential effector responses by circulatory and/or tissue PMNs. Tissue/peritoneal PMNs produced more O(-)(2), less intracellular elastase, and increased expression of CD11b/CD18 accompanied with increased adhesivity of MIP-2-stimulated PMNs to endothelial cells as compared to circulatory/blood PMNs. This differential effect was more pronounced following burn plus E. faecalis infection, indicating that the combined injury changed neutrophil functions. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Systems biology of neutrophil differentiation and immune response

DEFF Research Database (Denmark)

Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

2005-01-01

Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

[Effect of priming solution and ultrafiltration on post-operative bleeding and blood transfusion in cardiac surgery. Randomized controlled trial].

Science.gov (United States)

Olmos Rodríguez, M; Ballester Hernández, J A; Arteta Bárcenas, M T; Rodríguez Cerezo, A; Vidarte Ortiz de Artiñano, M A; Veiga Alameda, C

2015-02-01

Assess the effectiveness of priming the extracorporeal circulation system with albumin-mannitol combined with ultrafiltration during extracorporeal circulation to reduce post-operative bleeding and transfusion requirements in heart surgery, as well as its impact on the fluid balance, coagulation and hematocrit parameters, re-operation for bleeding, ICU, and hospital length of stay. A total of 134 patients scheduled for heart surgery were randomized to receive Ringer's lactate 1,500mL in the priming reservoir (group C), or mannitol 20% 250mL, albumin 20% 150mL and Ringer's lactate 1,100mL combined with ultrafiltration (group T). Bleeding volume, transfusions, fluid balance, coagulation, and hematology parameters were determined until 48h in the post-operative period. There was a reduction of postoperative bleeding in group T, 1,165±789mL vs 992±662mL (P=.17), and red blood cell concentrate transfusions, 694±843mL vs 413±605mL (P=.03). Intra-operative and post-operative fluid balance was significantly less positive in group T, with an overall balance of 2,292±2,152mL vs 5,388±2,834mL (P<.001). There were higher values of hemoglobin and hematocrit, intraoperative (P<.001), on admission to ICU (P=.001), and at 6h (P=.05) in group T, and lower INR at 6h (P=.01) and 24h (P=.02). Re-operation rate and length of stay in ICU were higher in group C, but not statiscally significant. The priming of extracorporeal reservoir with mannitol, albumin, and Ringer's lactate, combined with ultrafiltration, significantly improves intra- and post-operative fluid balance, resulting in a reduction in blood transfusions, with no significant decrease in post-operative bleeding, re-operation bleeding rate, and length of stay in the ICU. Copyright © 2014 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Diverse novel functions of neutrophils in immunity, inflammation, and beyond.

Science.gov (United States)

Mócsai, Attila

2013-07-01

Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10-20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellular pathogens such as viruses and mycobacteria. They have been shown to intimately shape the adaptive immune response at various levels, including marginal zone B cells, plasmacytoid dendritic cells and T cell populations, and even to control NK cell homeostasis. Neutrophils have been shown to mediate an alternative pathway of systemic anaphylaxis and to participate in allergic skin reactions. Finally, neutrophils were found to be involved in physiological and pathological processes beyond the immune system, such as diabetes, atherosclerosis, and thrombus formation. Many of those functions appear to be related to their unique ability to release neutrophil extracellular traps even in the absence of pathogens. This review summarizes those novel findings on versatile functions of neutrophils and how they change our view of neutrophil biology in health and disease.

Imaging neutrophil migration dynamics using micro-optical coherence tomography (Conference Presentation)

Science.gov (United States)

Chu, Kengyeh K.; Yonker, Lael; Som, Avira; Pazos, Michael; Kusek, Mark E.; Hurley, Bryan P.; Tearney, Guillermo J.

2016-03-01

Neutrophils are immune cells that undergo chemotaxis, detecting and migrating towards a chemical signal gradient. Neutrophils actively migrate across epithelial boundaries, interacting with the epithelium to selectively permit passage without compromising the epithelial barrier. In many inflammatory disorders, excessive neutrophil migration can cause damage to the epithelium itself. The signaling pathways and mechanisms that facilitate trans-epithelial migration are not fully characterized. Our laboratory has developed micro-optical coherence tomography (μOCT), which has 2 μm lateral resolution and 1 μm axial resolution. As a high-resolution native contrast modality, μOCT can directly visualize individual neutrophils as they interact with a cell layer cultured on a transwell filter. A chemoattractant can be applied to the apical side of inverted monolayer, and human neutrophils placed in the basolateral compartment, while μOCT captures 3D images of the chemotaxis. μOCT images can also generate quantitative metrics of migration volume to study the dependence of chemotaxis on monolayer cell type, chemoattractant type, and disease state of the neutrophils. For example, a disease known as leukocyte adhesion deficiency (LAD) can be simulated by treating neutrophils with antibodies that interfere with the CD18 receptor, a facilitator of trans-epithelial migration. We conducted a migration study of anti-CD18 treated and control neutrophils using T84 intestinal epithelium as a barrier. After one hour, μOCT time-lapse imaging indicated a strong difference in the fraction of neutrophils that remain attached to the epithelium after migration (0.67 +/- 0.12 attached anti-CD18 neutrophils, 0.23 +/- 0.08 attached control neutrophils, n = 6, p < 0.05), as well as a modest but non-significant decrease in total migration volume for treated neutrophils. We can now integrate μOCT-derived migration metrics with simultaneously acquired measurements of transepithelial electrical

[The significances of peripheral neutrophils CD(55) and myeloperoxidase expression in patients with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody associated vasculitis].

Science.gov (United States)

Zhou, X L; Zheng, M J; Shuai, Z W; Zhang, L; Zhang, M M; Chen, S Y

2017-06-01

Objective: To investigate the expression of CD(55) and myeloperoxidase (MPO) on neutrophils in patients with MPO-specific anti-neutrophil cytoplasmic antibody associated vasculitis(MPO-AAV), and analyze the relationship between the expression and clinical manifestation. Methods: Forty untreated patients with active MPO-AAV (patient group) and 30 healthy volunteers (control group) were enrolled in this study. The CD(55) on neutrophils and both membrane and cytoplasmic MPO were detected by flow cytometry. Serum fragment-from the activated complement factor B(Ba) and MPO were measured by ELISA. The clinical activity of vasculitis was valued by Birmingham vasculitis activity score-version 3(BVAS-V3). The significance of laboratory data was evaluated by Spearman correlation test and multivariate linear regression analysis. Results: (1)The mean fluorescence intensity(MFI) of CD(55) expressed on neutrophils was significantly higher than that in control group[4 068.6±2 306.0 vs 2 999.5±1 504.9, P =0.033]. Similar results of serum MPO and Ba in patient group were found compared to controls [500.0(381.0, 612.7) IU/L vs 286.9(225.5, 329.1) IU/L, P <0.001; 35.2(25.2, 79.5) ng/L vs 18.0(15.0, 28.0) ng/L, P <0.001], respectively. However, MIF of cytoplasmic MPO in patients was significantly lower than that of control group(1 577.1±1 175.9 vs 3 105.3±2 323.0, P =0.003) . (2) In patient group, cytoplasmic intensity of MPO was negatively associated with the serum levels of MPO( r =-0.710, P <0.001) and Ba ( r =-0.589, P =0.001). Moreover, serum MPO was positively associated with serum Ba( r =0.691, P <0.001). Membrane intensity of CD(55) on neutrophils was positively correlated with patient age ( r =0.514, P =0.001), C reactive protein ( r =0.376, P =0.018), peripheral neutrophils count ( r =0.485, P =0.001) and BVAS-V3 ( r =0.484, P =0.002), whereas negative correlation between membrane CD(55) and disease duration was seen ( r =-0.403, P =0.01). (3) The result of multiple

Modulation of neutrophil and monocyte function by recombinant human granulocyte macrophage colony-stimulating factor in patients with lymphoma

DEFF Research Database (Denmark)

Kharazmi, A; Nielsen, H; Hovgaard, D

1991-01-01

by up to 43-fold. rhGM-CSF treatment did not affect degranulation of the neutrophils as measured by release of vitamin B12 binding protein. Degree of modulation of neutrophil and monocyte function by rhGM-CSF was independent of rhGM-CSF dosages administered. These data suggest that phagocytic defence...... and chemiluminescence responses to f-Met-Leu-Phe, zymosan activated serum (ZAS) and opsonized zymosan (OZ) were determined. It was observed that chemotactic response of neutrophils to f-Met-Leu-Phe and ZAS was reduced, whereas the chemiluminescence response of both cell types to f-Met-Leu-Phe and zymosan was enhanced...

Neutrophils in traumatic brain injury (TBI): friend or foe?

Science.gov (United States)

Liu, Yang-Wuyue; Li, Song; Dai, Shuang-Shuang

2018-05-17

Our knowledge of the pathophysiology about traumatic brain injury (TBI) is still limited. Neutrophils, as the most abundant leukocytes in circulation and the first-line transmigrated immune cells at the sites of injury, are highly involved in the initiation, development, and recovery of TBI. Nonetheless, our understanding about neutrophils in TBI is obsolete, and mounting evidences from recent studies have challenged the conventional views. This review summarizes what is known about the relationships between neutrophils and pathophysiology of TBI. In addition, discussions are made on the complex roles as well as the controversial views of neutrophils in TBI.

Inhibition of neutrophil migration by aggregated immunoglobulin attached to micropore membranes.

Science.gov (United States)

Kemp, A S; Brown, S

1980-01-01

The effect of substrate-bound immunoglobulin on neutrophil migration was examined. Immunoglobulin aggregates bound to micropore membranes inhibited the neutrophil response to a chemotactic stimulus. This inhibition was reversed by the presence of aggregates in suspension suggesting competition between substrate-bound and free aggregates for neutrophil surface binding sites. The immobilization of neutrophils by substrate-bound aggregated immunoglobulin suggests a mechanism for the accumulation of neutrophils at sites of immune complex deposition and tissue-bound antibodies in vivo. PMID:7380477

Distinct Trypanosoma cruzi isolates induce activation and apoptosis of human neutrophils.

Directory of Open Access Journals (Sweden)

Luísa M D Magalhães

Full Text Available Neutrophils are critical players in the first line of defense against pathogens and in the activation of subsequent cellular responses. We aimed to determine the effects of the interaction of Trypanosoma cruzi with human neutrophils, using isolates of the two major discrete type units (DTUs associated with Chagas' disease in Latin America (clone Col1.7G2 and Y strain, DTU I and II, respectively. Thus, we used CFSE-stained trypomastigotes to measure neutrophil-T. cruzi interaction, neutrophil activation, cytokine expression and death, after infection with Col1.7G2 and Y strain. Our results show that the frequency of CFSE+ neutrophils, indicative of interaction, and CFSE intensity on a cell-per-cell basis were similar when comparing Col1.7G2 and Y strains. Interaction with T. cruzi increased neutrophil activation, as measured by CD282, CD284, TNF and IL-12 expression, although at different levels between the two strains. No change in IL-10 expression was observed after interaction of neutrophils with either strain. We observed that exposure to Y and Col1.7G2 caused marked neutrophil death. This was specific to neutrophils, since interaction of either strain with monocytes did not cause death. Our further analysis showed that neutrophil death was a result of apoptosis, which was associated with an upregulation of TNF-receptor, TNF and FasLigand, but not of Fas. Induction of TNF-associated neutrophil apoptosis by the different T. cruzi isolates may act as an effective common mechanism to decrease the host's immune response and favor parasite survival.

Depth of anaesthesia and post-operative cognitive dysfunction

DEFF Research Database (Denmark)

Steinmetz, J; Funder, K S; Dahl, B T

2010-01-01

A deep level of anaesthesia measured by the bispectral index has been found to improve processing speed as one aspect of cognitive function after surgery. The purpose of the present study was to assess the possible effect of the level of anaesthesia on post-operative cognitive dysfunction (POCD) 1...

Pseudomonas aeruginosa in Post-operative Wound Infections in ...

African Journals Online (AJOL)

The occurrence of post-operative wound infections was studied over a period of five months in the University College Hospital, Ibadan between February to July, 2003. Two hundred Surgical wounds were collected and routinely processed by Gram staining and culture in the Microbiology Laboratory. Of the 200 samples ...

Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice: Implications for Superficial Erosion.

Science.gov (United States)

Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K; Swirski, Filip K; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J; Libby, Peter

2017-06-23

Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion. In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis ( P <0.05). These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era. © 2017 American Heart Association, Inc.

Post-operative computed tomographic imaging of the shoulder joint

International Nuclear Information System (INIS)

Helweg, G.; Zur Nedden, D.; Wicke, K.; Knapp, R.; Oberhauser, A.; Resch, H.; Sperner, G.

1992-01-01

Between 1984 and 1990 312 patients underwent surgery for habitual or recurrent shoulder dislocation. Out then, 65 had a post-operative CT examination. This retrospective study was launched to demonstrate the value of CT in post-operative shoulder imaging. In most cases, CT was done using standardised techniques without contrast medium. Except in 4 cases, an intra-articular double-contrast technique was used. Evaluation was focused on 41 cases after implantation of a wedged bone graft in cases of primary or secondary flat glenoid or widening of a small glenoid with cortical consoles and bone block. The results demonstrate the effectiveness of standardised CT technique in that all necessary information concerning stabilisation of the shoulder joint, sufficient implant of bone grafts and assessment of correct inclination after osteotomy were obtained. (orig.)

Occurrence of pseudomonas aeruginosa in post-operative wound infection

International Nuclear Information System (INIS)

Oguntibeju, O.O.; Nwobu, R.A.U.

2004-01-01

Objective: To determine the prevalence of Pseudomonas aeruginosa in post-operative wound infection. Results: Out of the 60 bacterial isolates found in post-operative wound infection, 20 (33.3%) were Pseudomonas aeruginosa, followed by Staphylococcus aureus 13(21.7%), Klebsiella species 10(16.7%), Escherichia coli 7(11.7%), Atypical coliform 4(6.7%), Proteus species 4(6.7%), Streptococcus pyogenes 1(1.7%) and Enterococcus faecalis 1(1.7%) in the order. Pseudomonas aeruginosa infections was higher in female than male, ratio 3:2 and was found more among young and elderly debilitated patients. The in vitro sensitivity pattern of 20 isolates of Pseudomonas aeruginosa showed colistin (100%), gentamicin (75%), streptomycin (30%), and tetracycline (10%). Conclusion: The role of Pseudomonas aeruginosa as an agent of nosocomial infection is re-emphasised. (author)

The effect of midazolam on neutrophil mitogen-activated protein kinase.

LENUS (Irish Health Repository)

Ghori, Kamran

2010-06-01

Neutrophil p38 mitogen-activated protein kinase (MAPK) is a key enzyme in the intracellular signalling pathway that is responsible for many neutrophil functions, which are important in neutrophil-endothelial interaction. The imidazole compounds are inhibitors of this enzyme system. The objectives of this in-vitro investigation were to examine the effect of midazolam on neutrophil p38 MAPK activation (phosphorylation) following in-vitro ischaemia-reperfusion injury, and the expression of adhesion molecule CD11b\\/CD18.

Elimination of neutrophils in zymosan-induced ankle inflammation by etoposide

Directory of Open Access Journals (Sweden)

Viktoriya I. Milanova

2014-12-01

Full Text Available Neutrophils play a crucial role in the pathogenesis of joint inflammatory diseases such as rheumatoid arthritis (RA. Therefore their elimination and/or a functional inhibition might have beneficial or even therapeutic effects in these diseases. In the present study we exploited the cytotoxic action of etoposide to deplete neutrophils. We administrated the drug twice (at day -3 and day -1 to SCID mice having intact innate immunity and a fail in T- and B-cell maturation. Ankle inflammation was induced by the injection of zymosan (ZY. Joint damage was evaluated by histology grading system for cell infiltration and proteoglycan loss and degree of cartilage erosion. The frequencies of mature Ly6G+CD11b+ cells in bone marrow (BM were monitored at days -4, -2 and 0 by flow cytometry. At day 7 of ankle inflammation the amounts of pro-inflammatory cytokines tumor necrosis factor (TNF-α and interleukin (IL-17 were measured by enzyme-linked immunosorbent assay (ELISA. Histological analysis of the joint sections showed decreased scores for cell infiltration and cartilage proteoglycan loss and reduced cartilage erosion in drug-treated zymosan injected mice in comparison to untreated group with ankle inflammation. Etoposide diminished cell numbers in BM, inhibits granulopoiesis triggered by zymosan and decreased the frequencies of mature Ly6G+CD11b+ cells in BM and eliminated Ly6G+ cells from blood and synovial fluid. We observed reduced TNF-α and impaired IL-17 production in etoposide-treated ZY group. Our data provide a proof-of principle that the elimination of neutrophils might be exploited in a design of new therapeutic approaches for joint inflammatory diseases.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

International Nuclear Information System (INIS)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

2014-01-01

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

The role of neutrophil myeloperoxidase in models of lung tumor development.

Science.gov (United States)

Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Energy Technology Data Exchange (ETDEWEB)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Directory of Open Access Journals (Sweden)

Amy L. Rymaszewski

2014-05-01

Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

Effects of Wharton's jelly-derived mesenchymal stem cells on neonatal neutrophils

Directory of Open Access Journals (Sweden)

Khan I

2014-12-01

Full Text Available Imteyaz Khan,1 Liying Zhang,2 Moiz Mohammed,1 Faith E Archer,1 Jehan Abukharmah,1 Zengrong Yuan,2 S Saif Rizvi,1 Michael G Melek,1 Arnold B Rabson,1,2 Yufang Shi,2 Barry Weinberger,1 Anna M Vetrano1,21Department of Pediatrics, Division of Neonatology, Rutgers Robert Wood Johnson Medical School, 2Rutgers Child Health Institute of New Jersey, New Brunswick, NJ, USABackground: Mesenchymal stem cells (MSCs have been proposed as autologous therapy for inflammatory diseases in neonates. MSCs from umbilical cord Wharton's jelly (WJ-MSCs are accessible, with high proliferative capacity. The effects of WJ-MSCs on neutrophil activity in neonates are not known. We compared the effects of WJ-MSCs on apoptosis and the expression of inflammatory, oxidant, and antioxidant mediators in adult and neonatal neutrophils.Methods: WJ-MSCs were isolated, and their purity and function were confirmed by flow cytometry. Neutrophils were isolated from cord and adult blood by density centrifugation. The effects of neutrophil/WJ-MSC co-culture on apoptosis and gene and protein expression were measured.Results: WJ-MSCs suppressed neutrophil apoptosis in a dose-dependent manner. WJ-MSCs decreased gene expression of NADPH oxidase-1 in both adult and neonatal neutrophils, but decreased heme oxygenase-1 and vascular endothelial growth factor and increased catalase and cyclooxygenase-2 in the presence of lipopolysaccharide only in adult cells. Similarly, generation of interleukin-8 was suppressed in adult but not neonatal neutrophils. Thus, WJ-MSCs dampened oxidative, vascular, and inflammatory activity by adult neutrophils, but neonatal neutrophils were less responsive. Conversely, Toll-like receptor-4, and cyclooxygenase-2 were upregulated in WJ-MSCs only in the presence of adult neutrophils, suggesting an inflammatory MSC phenotype that is not induced by neonatal neutrophils.Conclusion: Whereas WJ-MSCs altered gene expression in adult neutrophils in ways suggesting anti

Earthworm coelomocyte extracellular traps: structural and functional similarities with neutrophil NETs.

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Homa, Joanna

2018-03-01

Invertebrate immunity is associated with natural mechanisms that include cellular and humoral elements, similar to those that play a role in vertebrate innate immune responses. Formation of extracellular traps (ETs) is a newly discovered mechanism to combat pathogens, operating not only in vertebrate leucocytes but also in invertebrate immune cells. The ET components include extracellular DNA (exDNA), antimicrobial proteins and histones. Formation of mammalian ETs depends on enzymes such as neutrophil elastase, myeloperoxidase, the citrullination of histones and protease activity. It was confirmed that coelomocytes-immunocompetent cells of the earthworm Eisenia andrei-are also able to release ETs in a protease-dependent manner, dependent or independent of the formation of reactive oxygen species and rearrangement of the cell cytoskeleton. Similar to vertebrate leukocytes (e.g., neutrophil), coelomocytes are responsible for many immune functions like phagocytosis, cytotoxicity and secretion of humoral factors. ETs formed by coelomocyte analogues to neutrophil ETs consist of exDNA, histone H3 and attached to these structures proteins, e.g., heat shock proteins HSP27. The latter fact confirms that mechanisms of ET release are conserved in evolution. The study on Annelida adds this animal group to the list of invertebrates capable of ET release, but most importantly provides insides into innate mechanisms of ET formation in lower animal taxa.

Post-operative cognitive dysfunction in the elderly: A prospective clinical study

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Nalini Kotekar

2014-01-01

Full Text Available Background and Aims: Aging population is a major demographic trend worldwide. Globally, 50% of all the elderly individuals are estimated to undergo atleast one surgical procedure and post-operative cognitive dysfunction (POCD is one of the most common and often poorly understood post-operative complications in this section of the population. This randomised prospective study was conducted to assess the post-operative cognitive status in the elderly undergoing non-cardiac surgery, evaluate the cognitive parameters affected, evaluate the potential risk factors and thereby analyse the potential for implementation of preventive strategies. Methods: This study was conducted on 200 patients aged 60 years or older scheduled for elective non-cardiac surgeries. The baseline cognitive status of the patients was assessed 2 days prior to the date of the surgery. The post-operative cognitive status was assessed on the 3 rd day, 7 th day and after 1 month. Statistical analysis was performed using SAS and SPSS. Results: The incidence of POCD showed a gradual decline from postoperative day 3 to 30. Females were found to be at significant risk in developing POCD. Advancing age and level of education emerged as dominant factors, while type of anaesthesia, duration of surgery, and presence of coexisting comorbidities had no influence on the incidence of cognitive dysfunction. Conclusion: POCD is a definite complication after surgery and anaesthesia in the elderly population. Gender emerged as a significant risk factor with increasing age as a dominating factor contributing to POCD.

Suppressed neutrophil function in children with acute lymphoblastic leukemia.

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Tanaka, Fumiko; Goto, Hiroaki; Yokosuka, Tomoko; Yanagimachi, Masakatsu; Kajiwara, Ryosuke; Naruto, Takuya; Nishimaki, Shigeru; Yokota, Shumpei

2009-10-01

Infection is a major obstacle in cancer chemotherapy. Neutropenia has been considered to be the most important risk factor for severe infection; however, other factors, such as impaired neutrophil function, may be involved in susceptibility to infection in patients undergoing chemotherapy. In this study, we analyzed neutrophil function in children with acute lymphoblastic leukemia (ALL). Whole blood samples were obtained from 16 children with ALL at diagnosis, after induction chemotherapy, and after consolidation chemotherapy. Oxidative burst and phagocytic activity of neutrophils were analyzed by flow cytometry. Oxidative burst of neutrophils was impaired in ALL patients. The percentage of neutrophils with normal oxidative burst after PMA stimulation was 59.0 +/- 13.2 or 70.0 +/- 21.0% at diagnosis or after induction chemotherapy, respectively, which was significantly lower compared with 93.8 +/- 6.1% in healthy control subjects (P = 0.00004, or 0.002, respectively); however, this value was normal after consolidation chemotherapy. No significant differences were noted in phagocytic activity in children with ALL compared with healthy control subjects. Impaired oxidative burst of neutrophils may be one risk factor for infections in children with ALL, especially in the initial periods of treatment.

Neutrophils Release Metalloproteinases during Adhesion in the Presence of Insulin, but Cathepsin G in the Presence of Glucagon

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Natalia V. Fedorova

2018-01-01

Full Text Available In patients with reperfusion after ischemia and early development of diabetes, neutrophils can attach to blood vessel walls and release their aggressive bactericide agents, which damage the vascular walls. Insulin and 17β-estradiol (E2 relieve the vascular complications observed in metabolic disorders. In contrast, glucagon plays an essential role in the pathophysiology of diabetes. We studied the effect of hormones on neutrophil secretion during adhesion to fibronectin. Amino acid analysis revealed that proteins secreted by neutrophils are characterized by a stable amino acid profile enriched with glutamate, leucine, lysine, and arginine. The total amount of secreted proteins defined as the sum of detected amino acids was increased in the presence of insulin and reduced in the presence of glucagon. E2 did not affect the amount of protein secretion. Proteome analysis showed that in the presence of insulin and E2, neutrophils secreted metalloproteinases MMP-9 and MMP-8 playing a key role in modulation of the extracellular matrix. In contrast, glucagon induced the secretion of cathepsin G, a key bactericide protease of neutrophils. Cathepsin G can promote the development of vascular complications because of its proinflammatory activity and ability to stimulate neutrophil adhesion via the proteolysis of surface receptors.

Selective inhibition of extracellular oxidants liberated from human neutrophils--A new mechanism potentially involved in the anti-inflammatory activity of hydroxychloroquine.

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Jančinová, Viera; Pažoureková, Silvia; Lucová, Marianna; Perečko, Tomáš; Mihalová, Danica; Bauerová, Katarína; Nosáľ, Radomír; Drábiková, Katarína

2015-09-01

Hydroxychloroquine is used in the therapy of rheumatoid arthritis or lupus erythematosus. Although these diseases are often accompanied by activation of neutrophils, there are still few data relating to the impact of hydroxychloroquine on these cells. We investigated the effect of orally administered hydroxychloroquine on neutrophil oxidative burst in rats with adjuvant arthritis. In human neutrophils, extra- and intracellular formation of oxidants, mobilisation of intracellular calcium and the phosphorylation of proteins regulating NADPH oxidase assembly were analysed. Administration of hydroxychloroquine decreased the concentration of oxidants in blood of arthritic rats. The inhibition was comparable with the reference drug methotrexate, yet it was not accompanied by a reduction in neutrophil count. When both drugs were co-applied, the effect became more pronounced. In isolated human neutrophils, treatment with hydroxychloroquine resulted in reduced mobilisation of intracellular calcium, diminished concentration of external oxidants and in decreased phosphorylation of Ca(2+)-dependent protein kinase C isoforms PKCα and PKCβII, which regulate activation of NADPH oxidase on plasma membrane. On the other hand, no reduction was observed in intracellular oxidants or in the phosphorylation of p40(phox) and PKCδ, two proteins directing the oxidase assembly to intracellular membranes. Hydroxychloroquine reduced neutrophil-derived oxidants potentially involved in tissue damage and protected those capable to suppress inflammation. The observed effects may represent a new mechanism involved in the anti-inflammatory activity of this drug. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy of port-site and intraperitoneal application of bupivacaine in reducing early post-laparoscopic cholecystectomy pain

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Ahmad, J.; Khan, Z.A.; Khan, A.

2015-01-01

The aim of this study was to assess the analgesic efficacy of Bupivacaine application at port-site and intraperitoneal infiltration in patients with laparoscopic cholecystectomy. Study Design: Randomized Controlled Clinical Trial. Place and Duration: The study was conducted at Rehman Medical Institute (RMI) Peshawar, Pakistan from June 2009 to June 2012. Materials and Methods: Patients who underwent elective laparoscopic cholecystectomy during the study period were included in the study. Eighty patients were randomized into two groups, study group and control group. The study group received 40 ml of 0.25% bupivacaine intraoperatively as intraperitoneal infiltration and local infiltration at the port sites. Pain assessment was done using visual analogue pain score (VAS) of 0-10 at fixed intervals during the first 24 hours post surgery. Results: The mean VAS score in the study group was less as compared to the control group throughout the 24 hours assessment period, however this difference was statistically significant (p<0.001) only during the first three assessments at 1 hour, 4 hours and 8 hours post surgery. The analgesia requirement was also significantly (p<0.001) decreased in the study group. Conclusion: Port site and intraperitoneal application of local anesthetic bupivacaine significantly reduced pain during the first 8 hours post surgery and total analgesia requirement was also significantly reduced. It is a simple and easily applicable technique which increases patient comfort and can be safely used to decrease post operative pain in patients undergoing laparoscopic cholecystectomy. (author)

Correlation of Leukocyte Count and Percentage of Segmented Neutrophils with Pathohistological Findings of Appendix in Children

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Marko Baskovic

2018-01-01

Full Text Available BackgroundAppendicitis is the most common indication for an emergency operation in children's age. Although none of the laboratory values has not high sensitivity and specificity for the diagnosis of appendicitis, leukocyte count and the percentage of segmented neutrophils are most commonly used. The aim of this study was to determine whether there is a statistically significant correlation between leukocyte count and the percentage of segmented neutrophils compared to the pathohistological finding of appendix in children. Materials and MethodsWe retrospectively analyzed the data in the period from 1 January 2016 to 31 December 2016. The analysis was made on 211 patients. Spearman's correlation coefficient (rs was calculated. We determined the specificity and sensitivity of leukocyte count and the percentage of segmented neutrophils used in the calculation of Alvorado and Pediatric Appendicitis score.ResultsThe results of the research have shown that the correlation between leukocyte count and the pathohistological findings is weak (rs = 0.29, p = 3.61*10-8, while there is no correlation between the percentage of segmented neutrophils and pathohistological findings (rs = 0.18, p = 7.08 *10-5. The sensitivity of leukocyte count is 93% and the specificity is 30%, while the sensitivity to the percentage of segmented neutrophils is 71% and the specificity is 50%. ROC analysis for leukocytes shows area under the curve of 0.648, while for segmented neutrophils of 0.574.ConclusionGiven the correlation results obtained, the clinical experience of physicians will still have one of the leading roles in diagnosing acute appendicitis in children.

Achyrocline satureioides (Lam. D.C. Hydroalcoholic Extract Inhibits Neutrophil Functions Related to Innate Host Defense

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Eric Diego Barioni

2013-01-01

Full Text Available Achyrocline satureioides (Lam. D.C. is a herb native to South America, and its inflorescences are popularly employed to treat inflammatory diseases. Here, the effects of the in vivo actions of the hydroalcoholic extract obtained from inflorescences of A. satureioides on neutrophil trafficking into inflamed tissue were investigated. Male Wistar rats were orally treated with A. satureioides extract, and inflammation was induced one hour later by lipopolysaccharide injection into the subcutaneous tissue. The number of leukocytes and the amount of chemotactic mediators were quantified in the inflammatory exudate, and adhesion molecule and toll-like receptor 4 (TLR-4 expressions and phorbol-myristate-acetate- (PMA- stimulated oxidative burst were quantified in circulating neutrophils. Leukocyte-endothelial interactions were quantified in the mesentery tissue. Enzymes and tissue morphology of the liver and kidney were evaluated. Treatment with A. satureioides extract reduced neutrophil influx and secretion of leukotriene B4 and CINC-1 in the exudates, the number of rolling and adhered leukocytes in the mesentery postcapillary venules, neutrophil L-selectin, β2-integrin and TLR-4 expression, and oxidative burst, but did not cause an alteration in the morphology and activities of liver and kidney. Together, the data show that A. satureioides extract inhibits neutrophil functions related to the innate response and does not cause systemic toxicity.

Changes in Neutrophil Functions in Astronauts

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Kaur, Indreshpal; Simons, Elizabeth R.; Castro, Victoria; Pierson, Duane L.

2002-01-01

Neutrophil functions (phagocytosis, oxidative burst, degranulation) and expression of surface markers involved in these functions were studied in 25 astronauts before and after 4 space shuttle missions. Space flight duration ranged from 5 to 11 days. Blood specimens were obtained 10 days before launch (preflight or L-10), immediately after landing (landing or R+0), and again at 3 days after landing (postflight or R+3). Blood samples were also collected from 9 healthy low-stressed subjects at 3 time points simulating a 10-day shuttle mission. The number of neutrophils increased at landing by 85 percent when compared to the preflight numbers. Neutrophil functions were studied in whole blood using flow cytometric methods. Phagocytosis of E.coli-FITC and oxidative burst capacity of the neutrophils following the 9 to 11 day missions were lower at all three sampling points than the mean values for control subjects. Phagocytosis and oxidative burst capacity of the astronauts was decreased even 10-days before space flight. Mission duration appears to be a factor in phagocytic and oxidative functions. In contrast, following the short-duration (5-days) mission, these functions were unchanged from control values. No consistent changes in degranulation were observed following either short or medium length space missions. The expression of CD16, CD32, CD11a, CD11b, CD11c, L-selectin and CD36 was measured and found to be variable. Specifically, CD16 and CD32 did not correlate with the changes in oxidative burst and phagocytosis. We can conclude from this study that the stresses associated with space flight can alter the important functions of neutrophils.

Neutrophilic nodules in the intestinal walls of Japanese monkeys associated with the neutrophil chemotactic activity of larval extracts and secretions of Oesophagostomum aculeatum.

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Horii, Y; Ishii, A; Owhashi, M; Miyoshi, M; Usui, M

1985-01-01

High neutrophil chemotactic activity was detected in the culture medium from Oesophagostomum aculeatum larvae in vitro using blind-well chambers with Millipore filters, and guinea pig leucocytes as indicator cells. Neutrophil chemotactic activity was also detected in the extract from larval worms in a dose dependent fashion. This activity was detected in the low molecular weight fractions adjacent to a sodium chloride marker by gel filtration on Sephadex G200. These results were further confirmed with monkey neutrophils. The possible role of this activity in the formation of granulomatous lesions rich in neutrophils found in O aculeatum infections in the Japanese monkey is discussed.

A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management

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Renée El-Gabalawy

2017-08-01

Full Text Available Introduction: Risk assessment for post-operative delirium (POD is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD magnetic resonance imaging (MRI carbon dioxide (CO2 stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD.Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure –Severity (CAM-S scoring instrument on days 0 (surgery through post-operative day 5, and patients were followed up at least 1 month post-operatively.Results: Six of 12 patients had no evidence of POD (non-POD. Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD (score ≥ 5/19 on the CAM-S. Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001. Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for

Operator- and software-related post-experimental variability and source of error in 2-DE analysis.

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Millioni, Renato; Puricelli, Lucia; Sbrignadello, Stefano; Iori, Elisabetta; Murphy, Ellen; Tessari, Paolo

2012-05-01

In the field of proteomics, several approaches have been developed for separating proteins and analyzing their differential relative abundance. One of the oldest, yet still widely used, is 2-DE. Despite the continuous advance of new methods, which are less demanding from a technical standpoint, 2-DE is still compelling and has a lot of potential for improvement. The overall variability which affects 2-DE includes biological, experimental, and post-experimental (software-related) variance. It is important to highlight how much of the total variability of this technique is due to post-experimental variability, which, so far, has been largely neglected. In this short review, we have focused on this topic and explained that post-experimental variability and source of error can be further divided into those which are software-dependent and those which are operator-dependent. We discuss these issues in detail, offering suggestions for reducing errors that may affect the quality of results, summarizing the advantages and drawbacks of each approach.

Heterogeneity in Neutrophil Microparticles Reveals Distinct Proteome and Functional Properties*

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Dalli, Jesmond; Montero-Melendez, Trinidad; Norling, Lucy V; Yin, Xiaoke; Hinds, Charles; Haskard, Dorian; Mayr, Manuel; Perretti, Mauro

2013-01-01

Altered plasma neutrophil microparticle levels have recently been implicated in a number of vascular and inflammatory diseases, yet our understanding of their actions is very limited. Herein, we investigate the proteome of neutrophil microparticles in order to shed light on their biological actions. Stimulation of human neutrophils, either in suspension or adherent to an endothelial monolayer, led to the production of microparticles containing >400 distinct proteins with only 223 being shared by the two subsets. For instance, postadherent microparticles were enriched in alpha-2 macroglobulin and ceruloplasmin, whereas microparticles produced by neutrophils in suspension were abundant in heat shock 70 kDa protein 1. Annexin A1 and lactotransferrin were expressed in both microparticle subsets. We next determined relative abundance of these proteins in three types of human microparticle samples: healthy volunteer plasma, plasma of septic patients and skin blister exudates finding that these proteins were differentially expressed on neutrophil microparticles from these samples reflecting in part the expression profiles we found in vitro. Functional assessment of the neutrophil microparticles subsets demonstrated that in response to direct stimulation neutrophil microparticles produced reactive oxygen species and leukotriene B4 as well as locomoted toward a chemotactic gradient. Finally, we investigated the actions of the two neutrophil microparticles subsets described herein on target cell responses. Microarray analysis with human primary endothelial cells incubated with either microparticle subset revealed a discrete modulation of endothelial cell gene expression profile. These findings demonstrate that neutrophil microparticles are heterogenous and can deliver packaged information propagating the activation status of the parent cell, potentially exerting novel and fundamental roles both under homeostatic and disease conditions. PMID:23660474

Regulation of apoptosis and priming of neutrophil oxidative burst by diisopropyl fluorophosphate

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Tsang Jennifer LY

2010-07-01

Full Text Available Abstract Background Diisopropyl fluorophosphate (DFP is a serine protease inhibitor that is widely used as an inhibitor of endogenous proteases in in vitro neutrophil studies. Its effects on neutrophil function are unclear. We sought to determine the biological effects of DFP on human neutrophil apoptosis and oxidative burst. Methods We isolated neutrophils from healthy volunteers, incubated them with DFP (2.5 mM, and evaluated neutrophil elastase (NE activity, neutrophil degranulation, apoptosis as reflected in hypodiploid DNA formation and exteriorization of phosphatidylserine (PS, processing and activity of caspases-3 and -8, oxidative burst activity and hydrogen peroxide release. Results Consistent with its activity as a serine protease inhibitor, DFP significantly inhibited NE activity but not the degranulation of azurophilic granules. DFP inhibited constitutive neutrophil apoptosis as reflected in DNA fragmentation, and the processing and activity of caspases-3 and -8. DFP also inhibited priming of neutrophils for oxidative burst activity and hydrogen peroxide release. However, DFP enhanced the exteriorization of PS in a dose-dependent manner. Conclusion We conclude that DFP exerts significant effects on neutrophil inflammatory function that may confound the interpretation of studies that use it for its antiprotease activity. We further conclude that endogenous proteases play a role in the biology of constitutive neutrophil apoptosis.

Ménage-à-trois: The ratio of bicarbonate to CO2 and the pH regulate the capacity of neutrophils to form NETs

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Christian Maueröder

2016-12-01

Full Text Available In this study we identified and characterized the potential of a high ratio of bicarbonate to CO2 and a moderately alkaline pH to render neutrophils prone to undergo neutrophil extracellular trap (NET formation. Both experimental settings increased the rate of spontaneous NET release and potentiated the NET-inducing capacity of phorbol esters (PMA, ionomycin, monosodium urate and LPS. In contrast, an acidic environment impaired neutrophil extracellular trap formation both spontaneous and induced. Our findings indicate that intracellular alkalinization of neutrophils in response to an alkaline environment leads to an increase of intracellular calcium and neutrophil activation. We further found that the anion channel blocker DIDS strongly reduced NET formation induced by bicarbonate. This finding suggests that the effects observed are due to a molecular program that renders neutrophils susceptible to neutrophil extracellular trap formation. Inflammatory foci are characterized by an acidic environment. Our data indicates that NET formation is favored by the higher pH at the border regions of inflamed areas. Moreover our findings highlight the necessity for strict pH control during assays of neutrophil extracellular trap formation.

Post-operative delirium is associated with increased 5-year mortality.

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Moskowitz, Eliza E; Overbey, Douglas M; Jones, Teresa S; Jones, Edward L; Arcomano, Todd R; Moore, John T; Robinson, Thomas N

2017-12-01

Post-operative delirium is associated with increased short term morbidity and mortality. Limited data exists on long term outcomes for older adults with postoperative delirium. We hypothesize that postoperative delirium is associated with increased 5-year mortality. Patients ≥50 years undergoing elective operations with planned intensive care unit (ICU) admissions were prospectively enrolled. The Confusion Assessment Method ICU (CAM-ICU) was used to diagnose delirium. The primary outcome variable was 5-year mortality. 172 patients were enrolled with an average age of 64 years. The overall incidence of delirium was 44% (75/172). At 5-years post-operatively, mortality was higher (59%, 41/70) in patients with delirium compared to patients without delirium (13%, 12/94, p delirium were 7.35 fold greater (95% CI: 1.49-36.18). Postoperative delirium is associated with increased long term mortality. Published by Elsevier Inc.

Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.

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Guiedem, Elise; Ikomey, George Mondinde; Nkenfou, Céline; Walter, Pefura-Yone Eric; Mesembe, Martha; Chegou, Novel Njweipi; Jacobs, Graeme Brendon; Okomo Assoumou, Marie Claire

2018-03-27

The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy. We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 10 6 /ml and 2.48 × 10 6 /ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.

Optimizing post-operative pain management in Latin America

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João Batista Santos Garcia

2017-07-01

Full Text Available Post-operative pain management is a significant problem in clinical practice in Latin America. Insufficient or inappropriate pain management is in large part due to insufficient knowledge, attitudes and education, and poor communications at various levels. In addition, the lack of awareness of the availability and importance of clear policies and guidelines for recording pain intensity, the use of specific analgesics and the proper approach to patient education have led to the consistent under-treatment of pain management in the region. However, these problems are not insurmountable and can be addressed at both the provider and patient level. Robust policies and guidelines can help insure continuity of care and reduce unnecessary variations in practice. The objective of this paper is to call attention to the problems associated with Acute Post-Operative Pain (APOP and to suggest recommendations for their solutions in Latin America. A group of experts on anesthesiology, surgery and pain developed recommendations that will lead to more efficient and effective pain management. It will be necessary to change the knowledge and behavior of health professionals and patients, and to obtain a commitment of policy makers. Success will depend on a positive attitude and the commitment of each party through the development of policies, programs and the promotion of a more efficient and effective system for the delivery of APOP services as recommended by the authors of this paper. The writing group believes that implementation of these recommendations should significantly enhance efficient and effective post-operative pain management in Latin America. Resumo: O controle da dor no período pós-operatório é um problema significativo na prática clínica na América Latina. O controle insuficiente ou inadequado da dor é devido, em grande parte, à insuficiência de conhecimento, atitudes e formação e à comunicação precária em vários níveis. Al

Ly6G-mediated depletion of neutrophils is dependent on macrophages.

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Bruhn, Kevin W; Dekitani, Ken; Nielsen, Travis B; Pantapalangkoor, Paul; Spellberg, Brad

2016-01-01

Antibody-mediated depletion of neutrophils is commonly used to study neutropenia. However, the mechanisms by which antibodies deplete neutrophils have not been well defined. We noticed that mice deficient in complement and macrophages had blunted neutrophil depletion in response to anti-Ly6G monoclonal antibody (MAb) treatment. In vitro, exposure of murine neutrophils to anti-Ly6G MAb in the presence of plasma did not result in significant depletion of cells, either in the presence or absence of complement. In vivo, anti-Ly6G-mediated neutrophil depletion was abrogated following macrophage depletion, but not complement depletion, indicating a requirement for macrophages to induce neutropenia by this method. These results inform the use and limitations of anti-Ly6G antibody as an experimental tool for depleting neutrophils in various immunological settings.

Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils

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Duerr, Mark A.; Aurora, Rajeev; Ford, David A.

2015-01-01

α-Chlorofatty aldehydes (α-ClFALDs) are produced by hypochlorous acid targeting plasmalogens during neutrophil activation. This study investigated the reaction of the α-chlorinated carbon of α-ClFALD with the nucleophile, GSH. Utilizing ESI/MS/MS, the reaction product of GSH and the 16-carbon α-ClFALD, 2-chlorohexadecanal (2-ClHDA), was characterized. The resulting conjugate of 2-ClHDA and GSH (HDA-GSH) has an intact free aldehyde, and the chlorine at the α-carbon is ejected. Stable isotope-labeled [d4]HDA-GSH was synthesized, which further confirmed the structure, and was used to quantify natural α-ClFALD conjugates of GSH (FALD-GSH) using reverse-phase LC with detection by ESI/MS/MS using selected reaction monitoring. HDA-GSH is elevated in RAW 264.7 cells treated with physiologically relevant concentrations of exogenous 2-ClHDA. Furthermore, PMA-treated primary human neutrophils have elevated levels of HDA-GSH and the conjugate of 2-chlorooctadecanal (2-ClODA) and GSH (ODA-GSH), as well as elevated levels of 2-ClHDA and 2-ClODA. Production of both conjugates in PMA-stimulated neutrophils was reduced by 3-aminotriazole pretreatment, which also blocks endogenous α-ClFALD production. Additionally, plasma FALD-GSH levels were elevated in the K/BxN mouse arthritis model. Taken together, these studies demonstrate novel peptidoaldehydes derived from GSH and α-ClFALD in activated human neutrophils and in vivo in K/BxN mice. PMID:25814023

Post-operative morbidity of the obese patient undergoing posterior ...

African Journals Online (AJOL)

Outcome measures: Post-operative morbidity measures – infection, seroma, pulmonary embolism, urinary tract infection, neurological injury and dural tears. Methods: One hundred consecutive patients undergoing posterior lumbar spine surgery were enrolled in the study. Three fellowship trained attending orthopaedic ...

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

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Ricci-Azevedo, Rafael; Oliveira, Aline Ferreira; Conrado, Marina C A V; Carvalho, Fernanda Caroline; Roque-Barreira, Maria Cristina

2016-04-01

ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1) immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS), form neutrophil extracellular traps (NETs) and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF) and interleukin-1beta (IL-1β) release; otherwise, transforming growth factor-beta (TGF-β) production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be considered an

Neutrophils Contribute to the Protection Conferred by ArtinM against Intracellular Pathogens: A Study on Leishmania major.

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Rafael Ricci-Azevedo

2016-04-01

Full Text Available ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has immunomodulatory activities through its interaction with N-glycans of immune cells, culminating with the establishment of T helper type 1 (Th1 immunity. This interaction protects mice against intracellular pathogens, including Leishmania major and Leishmania amazonensis. ArtinM induces neutrophils activation, which is known to account for both resistance to pathogens and host tissue injury. Although exacerbated inflammation was not observed in ArtinM-treated animals, assessment of neutrophil responses to ArtinM is required to envisage its possible application to design a novel immunomodulatory agent based on carbohydrate recognition. Herein, we focus on the mechanisms through which neutrophils contribute to ArtinM-induced protection against Leishmania, without exacerbating inflammation. For this purpose, human neutrophils treated with ArtinM and infected with Leishmania major were analyzed together with untreated and uninfected controls, based on their ability to eliminate the parasite, release cytokines, degranulate, produce reactive oxygen species (ROS, form neutrophil extracellular traps (NETs and change life span. We demonstrate that ArtinM-stimulated neutrophils enhanced L. major clearance and at least duplicated tumor necrosis factor (TNF and interleukin-1beta (IL-1β release; otherwise, transforming growth factor-beta (TGF-β production was reduced by half. Furthermore, ROS production and cell degranulation were augmented. The life span of ArtinM-stimulated neutrophils decreased and they did not form NETs when infected with L. major. We postulate that the enhanced leishmanicidal ability of ArtinM-stimulated neutrophils is due to augmented release of inflammatory cytokines, ROS production, and cell degranulation, whereas host tissue integrity is favored by their shortened life span and the absence of NET formation. Our results reinforce the idea that ArtinM may be

Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice – Implications for Superficial Erosion

Science.gov (United States)

Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K.; Swirski, Filip K.; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J.; Libby, Peter

2017-01-01

Rationale Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results : In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. TLR2 agonism activated luminal ECs, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing EC injury and local thrombosis (p<0.05). Conclusions These results implicate flow disturbance, neutrophils, and TLR2 signaling as mechanisms that contribute to superficial erosion, a cause of ACS of likely growing importance in the statin era. PMID:28428204

Do post-operative changes of neck-shaft angle and femoral component anteversion have an effect on clinical outcome following uncemented total hip arthroplasty?

Science.gov (United States)

Müller, M; Abdel, M P; Wassilew, G I; Duda, G; Perka, C

2015-12-01

The accurate reconstruction of hip anatomy and biomechanics is thought to be important in achieveing good clinical outcomes following total hip arthroplasty (THA). To this end some newer hip designs have introduced further modularity into the design of the femoral component such that neck-shaft angle and anteversion, which can be adjusted intra-operatively. The clinical effect of this increased modularity is unknown. We have investigated the changes in these anatomical parameters following conventional THA with a prosthesis of predetermined neck-shaft angle and assessed the effect of changes in the hip anatomy on clinical outcomes. In total, 44 patients (mean age 65.3 years (standard deviation (SD) 7); 17 male/27 female; mean body mass index 26.9 (kg/m²) (SD 3.1)) underwent a pre- and post-operative three-dimensional CT scanning of the hip. The pre- and post-operative neck-shaft angle, offset, hip centre of rotation, femoral anteversion, and stem alignment were measured. Additionally, a functional assessment and pain score were evaluated before surgery and at one year post-operatively and related to the post-operative anatomical changes. The mean pre-operative neck-shaft angle was significantly increased by 2.8° from 128° (SD 6.2; 119° to 147°) to 131° (SD 2.1; 127° to 136°) (p = 0.009). The mean pre-operative anteversion was 24.9° (SD 8; 7.9 to 39.1) and reduced to 7.4° (SD 7.3; -11.6° to 25.9°) post-operatively (p shaft angles was found with a significant decrease of the post-operative anteversion and slight increase of the neck-shaft angles, but without any impact on clinical outcome. ©2015 The British Editorial Society of Bone & Joint Surgery.

Safety relevant failure mechanisms in the post-operational phase; Sicherheitstechnisch relevante Fehlermechanismen in der Nachbetriebsphase

Energy Technology Data Exchange (ETDEWEB)

Mayer, Gerhard; Stiller, Jan Christopher; Roemer, Sarah

2017-03-15

When the 13{sup th} amendment of the Atomic Energy Act came into force, eight Germ an nuclear power plant units had their power operating licences revoked and are now in the so-called post operation phase. Of the remaining nuclear power plants, one have by now also entered the post operation phase, with those left in operation bound for entering this phase sometime between now and the end of 2022. Therefore, failure mechanisms that are particularly relevant for post operation were to be identified and described in the frame of the present project. To do so, three major steps were taken: Firstly, recent national and international pertinent literature was evaluated to obtain indications of failure mechanisms in the post operation phase. It turned out that most of the national and international literature deals with the general procedure of the transition from power operation to decommissioning and dismantling. However, there were also some documents providing detailed indications of possible failure mechanisms in post operation. This includes e.g. the release of radioactive materials caused by the drop of containers, chemical impacts on systems important to safety in connection with decontamination work, and corrosion in connection with the storage of the core in the spent fuel pool, with the latter leading to the jamming of the fuel assemblies in the storage racks and a possible reduction of coolant circulation. In a second step, three safety analyses of pressurised water reactors prepared by the respective plant operators were evaluated to identify failure mechanisms based on systems engineering. The failure mechanisms that were found here include e.g. faults in the boric acid concentration of the reactor coolant, damage to the equipment airlock upon the unloading of Castor casks, leakages in connection with primary system decontamination, and the drop of packages holding radioactive residual materials or waste with subsequent mobilisation of radioactive aerosols

Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

Directory of Open Access Journals (Sweden)

Vera Cavalcanti Araújo

Full Text Available Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM, as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

NR4A orphan nuclear receptor family members, NR4A2 and NR4A3, regulate neutrophil number and survival.

Science.gov (United States)

Prince, Lynne R; Prosseda, Svenja D; Higgins, Kathryn; Carlring, Jennifer; Prestwich, Elizabeth C; Ogryzko, Nikolay V; Rahman, Atiqur; Basran, Alexander; Falciani, Francesco; Taylor, Philip; Renshaw, Stephen A; Whyte, Moira K B; Sabroe, Ian

2017-08-24

The lifespan of neutrophils is plastic and highly responsive to factors that regulate cellular survival. Defects in neutrophil number and survival are common to both hematologic disorders and chronic inflammatory diseases. At sites of inflammation, neutrophils respond to multiple signals that activate protein kinase A (PKA) signaling, which positively regulates neutrophil survival. The aim of this study was to define transcriptional responses to PKA activation and to delineate the roles of these factors in neutrophil function and survival. In human neutrophil gene array studies, we show that PKA activation upregulates a significant number of apoptosis-related genes, the most highly regulated of these being NR4A2 and NR4A3 Direct PKA activation by the site-selective PKA agonist pair N6/8-AHA (8-AHA-cAMP and N6-MB-cAMP) and treatment with endogenous activators of PKA, including adenosine and prostaglandin E2, results in a profound delay of neutrophil apoptosis and concomitant upregulation of NR4A2/3 in a PKA-dependent manner. NR4A3 expression is also increased at sites of neutrophilic inflammation in a human model of intradermal inflammation. PKA activation also promotes survival of murine neutrophil progenitor cells, and small interfering RNA to NR4A2 decreases neutrophil production in this model. Antisense knockdown of NR4A2 and NR4A3 homologs in zebrafish larvae significantly reduces the absolute neutrophil number without affecting cellular migration. In summary, we show that NR4A2 and NR4A3 are components of a downstream transcriptional response to PKA activation in the neutrophil, and that they positively regulate neutrophil survival and homeostasis. © 2017 by The American Society of Hematology.

Mycobacteria attenuate nociceptive responses by formyl peptide receptor triggered opioid peptide release from neutrophils.

Directory of Open Access Journals (Sweden)

Heike L Rittner

2009-04-01

Full Text Available In inflammation, pain is regulated by a balance of pro- and analgesic mediators. Analgesic mediators include opioid peptides which are secreted by neutrophils at the site of inflammation, leading to activation of opioid receptors on peripheral sensory neurons. In humans, local opioids and opioid peptides significantly downregulate postoperative as well as arthritic pain. In rats, inflammatory pain is induced by intraplantar injection of heat inactivated Mycobacterium butyricum, a component of complete Freund's adjuvant. We hypothesized that mycobacterially derived formyl peptide receptor (FPR and/or toll like receptor (TLR agonists could activate neutrophils, leading to opioid peptide release and inhibition of inflammatory pain. In complete Freund's adjuvant-induced inflammation, thermal and mechanical nociceptive thresholds of the paw were quantified (Hargreaves and Randall-Selitto methods, respectively. Withdrawal time to heat was decreased following systemic neutrophil depletion as well as local injection of opioid receptor antagonists or anti-opioid peptide (i.e. Met-enkephalin, beta-endorphin antibodies indicating an increase in pain. In vitro, opioid peptide release from human and rat neutrophils was measured by radioimmunoassay. Met-enkephalin release was triggered by Mycobacterium butyricum and formyl peptides but not by TLR-2 or TLR-4 agonists. Mycobacterium butyricum induced a rise in intracellular calcium as determined by FURA loading and calcium imaging. Opioid peptide release was blocked by intracellular calcium chelation as well as phosphoinositol-3-kinase inhibition. The FPR antagonists Boc-FLFLF and cyclosporine H reduced opioid peptide release in vitro and increased inflammatory pain in vivo while TLR 2/4 did not appear to be involved. In summary, mycobacteria activate FPR on neutrophils, resulting in tonic secretion of opioid peptides from neutrophils and in a decrease in inflammatory pain. Future therapeutic strategies may aim

Comparative Evaluation of Immediate Post-Operative Sequelae after Surgical Removal of Impacted Mandibular Third Molar with or without Tube Drain - Split-Mouth Study.

Science.gov (United States)

Kumar, Barun; Bhate, Kalyani; Dolas, R S; Kumar, Sn Santhosh; Waknis, Pushkar

2016-12-01

Third molar surgery is one of the most common surgical procedures performed in general dentistry. Post-operative variables such as pain, swelling and trismus are major concerns after impacted mandibular third molar surgery. Use of passive tube drain is supposed to help reduce these immediate post-operative sequelae. The current study was designed to compare the effect of tube drain on immediate post-operative sequelae following impacted mandibular third molar surgery. To compare the post-operative sequelae after surgical removal of impacted mandibular third molar surgery with or without tube drain. Thirty patients with bilateral impacted mandibular third molars were divided into two groups: Test (with tube drain) and control (without tube drain) group. In the test group, a tube drain was inserted through the releasing incision, and kept in place for three days. The control group was left without a tube drain. The post-operative variables like, pain, swelling, and trismus were calculated after 24 hours, 72 hours, 7 days, and 15 days in both the groups and analyzed statistically using chi-square and t-test analysis. The test group showed lesser swelling as compared to control group, with the swelling variable showing statistically significant difference at post-operative day 3 and 7 (p≤ 0.05) in both groups. There were no statistically significant differences in pain and trismus variables in both the groups. The use of tube drain helps to control swelling following impacted mandibular third molar surgery. However, it does not have much effect on pain or trismus.

Milk fat globule-epidermal growth factor-factor VIII-derived peptide MSP68 is a cytoskeletal immunomodulator of neutrophils that inhibits Rac1.

Science.gov (United States)

Hendricks, Louie; Aziz, Monowar; Yang, Weng-Lang; Nicastro, Jeffrey; Coppa, Gene F; Symons, Marc; Wang, Ping

2017-02-01

Prolonged neutrophil infiltration leads to exaggerated inflammation and tissue damage during sepsis. Neutrophil migration requires rearrangement of their cytoskeleton. Milk fat globule-epidermal growth factor-factor VIII-derived short peptide 68 (MSP68) has recently been shown to be beneficial in sepsis-induced tissue injury and mortality. We hypothesize that MSP68 inhibits neutrophil migration by modulating small GTPase Rac1-dependent cytoskeletal rearrangements. Bone marrow-derived neutrophils (BMDNs) or whole lung digest isolated neutrophils were isolated from 8 to 10 wk old C57BL/6 mice by Percoll density gradient centrifugation. The purity of BMDN was verified by flow cytometry with CD11b/Gr-1 staining. Neutrophils were stimulated with N-formylmethionine-leucine-phenylalanine (f-MLP) (10 nM) in the presence or absence of MSP68 at 10 nM or cecal ligation and puncture (CLP) was used to induce sepsis, and MSP68 was administered at 1 mg/kg intravenously. Cytoskeletal organization was assessed by phalloidin staining, followed by analysis using fluorescence microscopy. Activity of the Rac1 GTPase in f-MLP or CLP-activated BMDN in the presence or absence of MSP68 was assessed by GTPase enzyme-linked immunosorbent assay. Mitogen-activated protein (MAP) kinase activity was determined by western blot densitometry. BMDN treatment with f-MLP increased cytoskeletal remodeling as revealed by the localization of filamentous actin to the periphery of the neutrophil. By contrast, cells pretreated with MSP68 had considerably reduced filamentous actin polymerization. Cytoskeletal spreading is associated with the activation of the small GTPase Rac1. We found BMDN-treated with f-MLP or that were exposed to sepsis by CLP had increased Rac1 signaling, whereas the cells pretreated with MSP68 had significantly reduced Rac1 activation (P Rac1-MAP kinase-mediated neutrophil motility. Thus, MSP68 is a novel therapeutic candidate for regulating inflammation and tissue damage caused

In vivo activation of equine eosinophils and neutrophils by experimental Strongylus vulgaris infections.

Science.gov (United States)

Dennis, V A; Klei, T R; Chapman, M R; Jeffers, G W

1988-12-01

Eosinophils and neutrophils from ponies with Strongylus vulgaris-induced eosinophilia (eosinophilic ponies; activated eosinophils and neutrophils) were assayed in vitro for chemotactic and chemokinetic responses to zymosan-activated serum (ZAS) using the filter system in Boyden chambers, for Fc and complement (C) receptors using the EA and EAC-rosette assays, respectively, and for phagocytic and bactericidal activities using opsonized Escherichia coli and the acridine orange method. The responses of activated eosinophils and neutrophils in the above assays were compared with those of eosinophils and neutrophils from S. vulgaris-naive ponies without eosinophilia (noneosinophilic ponies; nonactivated eosinophils and neutrophils). Differences in cell density following centrifugation in a continuous Percoll gradient were used to further characterize the heterogeneity of activated eosinophils and neutrophils. Activated and nonactivated eosinophils demonstrated similar chemotactic responses to ZAS while activated and nonactivated neutrophils demonstrated similar chemokinetic responses to ZAS. A higher percentage of activated eosinophils and neutrophils expressed Fc and C receptors compared with nonactivated cells (P less than 0.05). Generally, higher percentages of eosinophils and neutrophils expressed C than Fc receptors. However, the percentage of neutrophils with both receptors was higher than that of eosinophils. Phagocytosis and killing of E. coli by either type of eosinophil were not consistently observed. Both activated and nonactivated neutrophils phagocytized E. coli and significant differences between the two cell types were not observed. The bacterial activity, however, of activated neutrophils was significantly greater than that obtained using nonactivated neutrophils (P less than 0.05). Activated eosinophils and neutrophils were both separated into two distinct fractions based on differences in cell densities. A higher percentage of band 2 eosinophils

Collective Inference based Data Analytics System for Post Operations Analysis, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — Current-day capabilities for performing post operations analysis (POA) of air traffic operations at airports, airlines and FAA facilities are mostly limited to...

File list: Unc.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.50.AllAg.Neutrophils hg19 Unclassified Blood Neutrophils SRX956546,SRX95655...2,SRX956549 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.50.AllAg.Neutrophils.bed ...

File list: Unc.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.05.AllAg.Neutrophils hg19 Unclassified Blood Neutrophils SRX956546,SRX95655...2,SRX956549 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.05.AllAg.Neutrophils.bed ...

File list: Unc.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available Unc.Bld.10.AllAg.Neutrophils hg19 Unclassified Blood Neutrophils SRX956552,SRX95654...9,SRX956546 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Bld.10.AllAg.Neutrophils.bed ...

Post-operative treatment of endometrial carcinoma. Chapter 20

International Nuclear Information System (INIS)

Kuipers, Tj.; Star, W.M.

1980-01-01

The alternative forms of post-operative radiotherapy given in Rotterdam for endometrial carcinoma are described. Patients with infiltration involving less than half the thickness of the myometrium are treated with low dose-rate 137 Cs afterloading techniques. However, in patients with deep infiltration, a combination of high dose-rate Cathetron treatment and external irradiation is used. (U.K.)

Depth of anaesthesia and post-operative cognitive dysfunction

DEFF Research Database (Denmark)

Steinmetz, J; Funder, K S; Dahl, B T

2010-01-01

A deep level of anaesthesia measured by the bispectral index has been found to improve processing speed as one aspect of cognitive function after surgery. The purpose of the present study was to assess the possible effect of the level of anaesthesia on post-operative cognitive dysfunction (POCD) 1...... week after surgery, as assessed by a neuropsychological test battery....

A fatal case of post-operative pulmonary thromboembolism with cosmetic liposuction.

Science.gov (United States)

Uemura, Koichi; Kikuchi, Yousuke; Shintani-Ishida, Kaori; Nakajima, Makoto; Yoshida, Ken-ichi

2006-01-01

Pulmonary thromboembolism (PTE) has been regarded as rare in Japan. However, PTE has been increasingly recognised because either of increased incidence, diagnostic progress, or social recognition. Recently, 10 Japanese Medical Associations have submitted preventive guidelines for PTE in post-operative patients and the government decided to fund this, as results of the increase in cases and concern regarding medical negligence. A fatal case of PTE after liposuction is reported. A female patient was in the home toilet after two days of immobilization following day-surgery liposuction. Clinicians must be aware of appropriate methods for the prevention of post operative PTE with cosmetic surgery.

Spontaneous neutrophil activation in HTLV-1 infected patients

Directory of Open Access Journals (Sweden)

Jaqueline B. Guerreiro

Full Text Available Human T cell lymphotropic Virus type-1 (HTLV-1 induces lymphocyte activation and proliferation, but little is known about the innate immune response due to HTLV-1 infection. We evaluated the percentage of neutrophils that metabolize Nitroblue tetrazolium (NBT to formazan in HTLV-1 infected subjects and the association between neutrophil activation and IFN-gamma and TNF-alpha levels. Blood was collected from 35 HTLV-1 carriers, from 8 patients with HAM/TSP (HTLV-1- associated myelopathy; 22 healthy individuals were evaluated for spontaneous and lipopolysaccharide (LPS-stimulated neutrophil activity (reduction of NBT to formazan. The production of IFN-gamma and TNF-alpha by unstimulated mononuclear cells was determined by ELISA. Spontaneous NBT levels, as well as spontaneous IFN-gamma and TNF-alpha production, were significantly higher (p<0.001 in HTLV-1 infected subjects than in healthy individuals. A trend towards a positive correlation was noted, with increasing percentage of NBT positive neutrophils and levels of IFN-gamma. The high IFN-gamma producing HTLV-1 patient group had significantly greater NBT than healthy controls, 43±24% and 17±4.8% respectively (p< 0.001, while no significant difference was observed between healthy controls and the low IFN-gamma-producing HTLV-1 patient group (30±20%. Spontaneous neutrophil activation is another marker of immune perturbation resulting from HTLV-1 infection. In vivo activation of neutrophils observed in HTLV-1 infected subjects is likely to be the same process that causes spontaneous IFN-gamma production, or it may partially result from direct IFN-gamma stimulation.

Effect of fluticasone propionate on neutrophil chemotaxis, superoxide generation, and extracellular proteolytic activity in vitro.

Science.gov (United States)

Llewellyn-Jones, C G; Hill, S L; Stockley, R A

1994-03-01

Corticosteroids are widely used in the treatment of many inflammatory conditions but the exact mode of action on neutrophil function is uncertain. Fluticasone propionate is a new topically active synthetic steroid which can be measured in body fluids and which undergoes first pass metabolism. The effects of fluticasone propionate on the function of neutrophils isolated from normal, healthy control subjects and on the chemotactic activity of sputum sol phase were assessed. Preincubation of neutrophils with fluticasone propionate reduced the chemotactic response to 10(-8) mol/l F-Met-Leu-Phe (FMLP) and to a 1:5 dilution of sputum sol phase in a dose dependent manner. Furthermore, when fluticasone propionate was added to sputum from eight patients with stable chronic obstructive bronchitis the chemotactic activity of a 1:5 dilution of the sol phase fell from a mean (SE) value of 22.2 (1.21) cells/field to 19.6 (0.89), 17.1 (0.74), and 11.9 (0.6) cells field at 1 mumol/l, 10 mumol/l, and 100 mumol/l, respectively. In further experiments fluticasone propionate preincubated with neutrophils inhibited fibronectin degradation by resting cells and by cells stimulated by FMLP (15.2% inhibition of resting cells, 5.1% inhibition of stimulated cells with 1 mumol/l fluticasone propionate, 24% and 18.7% inhibition respectively at 100 mumol/l fluticasone propionate. Fluticasone propionate had no effect on generation of superoxide anion by resting or stimulated cells. These results indicate that fluticasone propionate has a direct suppressive effect on several aspects of neutrophil function and may suggest a role for this agent in the modulation of neutrophil mediated damage to connective tissue.

Predictors of post operative bleeding and blood transfusion in ...

African Journals Online (AJOL)

blood requirements. Objective: To evaluate the impact of some perioperative predictors of post-operative bleeding, and blood transfusion after heart surgery and offer suggestions on preventive measures. Design and Methods: A prospective analytical study. The perioperative factors studied were haemoglobin level, ...

Neutrophils Infiltrate the Spinal Cord Parenchyma of Rats with Experimental Diabetic Neuropathy

Directory of Open Access Journals (Sweden)

Victoria L. Newton

2017-01-01

Full Text Available Spinal glial cell activation and cytokine secretion have been implicated in the etiology of neuropathic pain in a number of experimental models, including diabetic neuropathy. In this study, streptozotocin- (STZ- induced diabetic rats were either untreated or treated with gabapentin (50 mg/kg/day by gavage for 2 weeks, from 6 weeks after STZ. At 8 weeks after STZ, hypersensitivity was confirmed in the untreated diabetic rats as a reduced response threshold to touch, whilst mechanical thresholds in gabapentin-treated diabetic rats were no different from controls. Diabetes-associated thermal hypersensitivity was also ameliorated by gabapentin. We performed a cytokine profiling array in lumbar spinal cord samples from control and diabetic rats. This revealed an increase in L-selectin, an adhesion molecule important for neutrophil transmigration, in the spinal cord of diabetic rats but not diabetic rats treated with gabapentin. Furthermore, we found an increase in the number of neutrophils present in the parenchyma of the spinal cord, which was again ameliorated in gabapentin-treated diabetic rats. Therefore, we suggest that dysregulated spinal L-selectin and neutrophil infiltration into the spinal cord could contribute to the pathogenesis of painful diabetic neuropathy.

Pre-operative use of anti-TNF-alpha agents and the risk of post-operative complications in patients with Crohn's disease--a nationwide cohort study

DEFF Research Database (Denmark)

Nørgård, Bente Mertz; Nielsen, J.; Qvist, N.

2013-01-01

BACKGROUND: A possible negative role of pre-operative use of antitumour necrosis factor-alpha (anti-TNF-alpha) agents on post-operative outcomes in Crohn's disease (CD) patients is still debated. AIM: To examine the impact of pre-operative anti-TNF-alpha agents on post-operative outcomes 30 and 6...

SiMA: A simplified migration assay for analyzing neutrophil migration.

Science.gov (United States)

Weckmann, Markus; Becker, Tim; Nissen, Gyde; Pech, Martin; Kopp, Matthias V

2017-07-01

In lung inflammation, neutrophils are the first leukocytes migrating to an inflammatory site, eliminating pathogens by multiple mechanisms. The term "migration" describes several stages of neutrophil movement to reach the site of inflammation, of which the passage of the interstitium and basal membrane of the airway are necessary to reach the site of bronchial inflammation. Currently, several methods exist (e.g., Boyden Chamber, under-agarose assay, or microfluidic systems) to assess neutrophil mobility. However, these methods do not allow for parameterization on single cell level, that is, the individual neutrophil pathway analysis is still considered challenging. This study sought to develop a simplified yet flexible method to monitor and quantify neutrophil chemotaxis by utilizing commercially available tissue culture hardware, simple video microscopic equipment and highly standardized tracking. A chemotaxis 3D µ-slide (IBIDI) was used with different chemoattractants [interleukin-8 (IL-8), fMLP, and Leukotriene B4 (LTB 4 )] to attract neutrophils in different matrices like Fibronectin (FN) or human placental matrix. Migration was recorded for 60 min using phase contrast microscopy with an EVOS ® FL Cell Imaging System. The images were normalized and texture based image segmentation was used to generate neutrophil trajectories. Based on these spatio-temporal information a comprehensive parameter set is extracted from each time series describing the neutrophils motility, including velocity and directness and neutrophil chemotaxis. To characterize the latter one, a sector analysis was employed enabling the quantification of the neutrophils response to the chemoattractant. Using this hard- and software framework we were able to identify typical migration profiles of the chemoattractants IL-8, fMLP, and LTB 4 , the effect of the matrices FN versus HEM as well as the response to different medications (Prednisolone). Additionally, a comparison of four asthmatic and

Controlling Acute Post-operative Pain in Iranian Children with using of Music Therapy

Directory of Open Access Journals (Sweden)

Mojtaba Miladinia

2016-05-01

Full Text Available Background: Despite the development of pediatric post-operative pain management and use of analgesic/narcotic drugs, post-operative pain remains as a common problem. Some studies suggested, the most effective approach to controlling immediate post-operative pain may include a combination of drug agents and non-drug methods. The aim of this study was to investigate the effect of music therapy on the acute post-operative pain in Iranian children.  Materials and Methods: A quasi-experimental, repeated measure design was used. In this study, 63 children were placed in the music and control groups. In the music group, pain intensity was measured before start intervention (baseline. Then, this group listened to two non-speech music for 20 minutes. Then, pain intensity was measured with numeric rating scale, immediately after intervention, 1 hour, 3 hours and 6 hours after intervention, respectively. Also, in the control group, pain intensity was measured in times similar to music group. Results: The mean of pain intensity did not significantly different between the 2 groups at baseline (P>0.05. The results of repeated measure ANOVA showed that, trend of pain intensity between 2 groups was significant (P

Early versus delayed post-operative bathing or showering to prevent wound complications.

Science.gov (United States)

Toon, Clare D; Sinha, Sidhartha; Davidson, Brian R; Gurusamy, Kurinchi Selvan

2015-07-23

Many people undergo surgical operations during their life-time, which result in surgical wounds. After an operation the incision is closed using stiches, staples, steri-strips or an adhesive glue. Usually, towards the end of the surgical procedure and before the patient leaves the operating theatre, the surgeon covers the closed surgical wound using gauze and adhesive tape or an adhesive tape containing a pad (a wound dressing) that covers the surgical wound. There is currently no guidance about when the wound can be made wet by post-operative bathing or showering. Early bathing may encourage early mobilisation of the patient, which is good after most types of operation. Avoiding post-operative bathing or showering for two to three days may result in accumulation of sweat and dirt on the body. Conversely, early washing of the surgical wound may have an adverse effect on healing, for example by irritating or macerating the wound, and disturbing the healing environment. To compare the benefits (such as potential improvements to quality of life) and harms (potentially increased wound-related morbidity) of early post-operative bathing or showering (i.e. within 48 hours after surgery, the period during which epithelialisation of the wound occurs) compared with delayed post-operative bathing or showering (i.e. no bathing or showering for over 48 hours after surgery) in patients with closed surgical wounds. We searched The Cochrane Wounds Group Specialised Register (30th June 2015); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); The Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process & Other Non-Indexed Citations); Ovid EMBASE; EBSCO CINAHL; the metaRegister of Controlled Trials (mRCT) and the International Clinical Trials Registry Platform (ICTRP). We considered all randomised trials conducted in patients who had undergone any surgical procedure and had surgical closure of

Post-operative serious adverse events in a mixed surgical population

DEFF Research Database (Denmark)

Hansen, M S; Petersen, E E; Dahl, J B

2016-01-01

BACKGROUND: The number of surgical procedures is increasing, and knowledge of surgical risk factors, post-operative mortality and serious adverse events (SAE) is essential. The aim with our study was to determine the risk of a composite outcome of post-operative: death; myocardial infarction...... or gynaecological surgery was conducted retrieving data from The Danish Civil Registration System and the National Patient Register. Total observation time was from January 1, 2012 to June 6, 2013. RESULTS: A total7449 adult patients were included in the final analysis. The risk of the composite outcome during...... of 8.3% (7.8-9.0). The results are applicable in estimations of adequate sample sizes in future clinical trials investigating effects of interventions on SAEs....

File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.50.AllAg.Neutrophils mm9 Histone Blood Neutrophils SRX760581,SRX760584,SRX7...60583,SRX760580,SRX760582 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.50.AllAg.Neutrophils.bed ...

File list: His.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.20.AllAg.Neutrophils mm9 Histone Blood Neutrophils SRX760584,SRX760581,SRX7...60583,SRX760580,SRX760582 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.20.AllAg.Neutrophils.bed ...

File list: His.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.10.AllAg.Neutrophils mm9 Histone Blood Neutrophils SRX760584,SRX760583,SRX7...60581,SRX760582,SRX760580 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.10.AllAg.Neutrophils.bed ...

File list: His.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.05.AllAg.Neutrophils mm9 Histone Blood Neutrophils SRX760584,SRX760581,SRX7...60583,SRX760582,SRX760580 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Neutrophils.bed ...

Post-operative pain management in paediatric surgery at Sylvanus Olympio University Teaching Hospital, Togo

Directory of Open Access Journals (Sweden)

Hamza Doles Sama

2014-01-01

Full Text Available Background: The aim of this study was to evaluate pain management in paediatric surgery at Sylvanus Olympio University Teaching Hospital, Lome. Patients and Methods: A prospective descriptive study was conducted in the Department of Anaesthesiology and Intensive Care at Sylvanus Olympio teaching hospital from 1 January to 30 June 2012. Data collected include: demography, type of surgery, American Society of Anaesthesiologists (ASA classification, anaesthetic protocol, analgesia technique, post-operative complications and cost of analgesia. Results: The study includes 106 post-operative children. Abdominal surgery was performed in 41.5% and orthopaedic surgery in 31.1%. A total of 75% of patients were classified ASA 1. General anaesthesia (GA was performed in 88%. Anaesthetists supervised post-operative care in 21.7% cases. Multimodal analgesia was used in every case and 12% of patients received a regional block. The most frequently unwanted effects of analgesics used were nausea and/or vomiting in 12.3%. At H24, child under 7 years have more pain assessment than those from 7 to 15 years (46% vs 24% and this difference was statistically significant (chi-square = 4.7598; P = 0.0291 < 0.05. The average cost of peri-operative analgesia under loco regional analgesia (LRA versus GA during the first 48 h post-operative was US $23 versus $46. Conclusion: Our study showed that post-operative pain management in paediatric surgery is often not well controlled and paediatric loco regional analgesia technique is under practiced in sub Saharan Africa.

RhoA determines disease progression by controlling neutrophil motility and restricting hyperresponsiveness

DEFF Research Database (Denmark)

Jennings, Richard T; Strengert, Monika; Hayes, Patti

2014-01-01

Neutrophil responses are central to host protection and inflammation. Neutrophil activation follows a two-step process where priming amplifies responses to activating stimuli. Priming is essential for life span extension, chemotaxis and respiratory burst activity. Here we show that the cytoskeletal...... organizer RhoA suppresses neutrophil priming via formins. Premature granule exocytosis in Rho-deficient neutrophils activated numerous signaling pathways and amplified superoxide generation. Deletion of Rho altered front-to-back coordination by simultaneously increasing uropod elongation, leading edge...... neutrophils exacerbated LPS-mediated lung injury, deleting Rho in innate immune cells was highly protective in Influenza A virus infection. Hence, Rho is a key regulator of disease progression by maintaining neutrophil quiescence and suppressing hyperresponsiveness....

Mycobacterium tuberculosis Cell Wall Fragments Released upon Bacterial Contact with the Human Lung Mucosa Alter the Neutrophil Response to Infection.

Science.gov (United States)

Scordo, Julia M; Arcos, Jesús; Kelley, Holden V; Diangelo, Lauren; Sasindran, Smitha J; Youngmin, Ellie; Wewers, Mark D; Wang, Shu-Hua; Balada-Llasat, Joan-Miquel; Torrelles, Jordi B

2017-01-01

In 2016, the World Health Organization reported that one person dies of tuberculosis (TB) every 21 s. A host environment that Mycobacterium tuberculosis ( M.tb ) finds during its route of infection is the lung mucosa bathing the alveolar space located in the deepest regions of the lungs. We published that human lung mucosa, or alveolar lining fluid (ALF), contains an array of hydrolytic enzymes that can significantly alter the M.tb surface during infection by cleaving off parts of its cell wall. This interaction results in two different outcomes: modifications on the M.tb cell wall surface and release of M.tb cell wall fragments into the environment. Typically, one of the first host immune cells at the site of M.tb infection is the neutrophil. Neutrophils can mount an extracellular and intracellular innate immune response to M.tb during infection. We hypothesized that exposure of neutrophils to ALF-induced M.tb released cell wall fragments would prime neutrophils to control M.tb infection better. Our results show that ALF fragments activate neutrophils leading to an increased production of inflammatory cytokines and oxidative radicals. However, neutrophil exposure to these fragments reduces production of chemoattractants (i.e., interleukin-8), and degranulation, with the subsequent reduction of myeloperoxidase release, and does not induce cytotoxicity. Unexpectedly, these ALF fragment-derived modulations in neutrophil activity do not further, either positively or negatively, contribute to the intracellular control of M.tb growth during infection. However, secreted products from neutrophils primed with ALF fragments are capable of regulating the activity of resting macrophages. These results indicate that ALF-induced M.tb fragments could further contribute to the control of M.tb growth and local killing by resident neutrophils by switching on the total oxidative response and limiting migration of neutrophils to the infection site.

Survival of Peripheral Blood Neutrophil Following Treatment with Soluble Factors from Rat Mesenchymal Stem Cells

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S Hamounnavard

2014-11-01

Full Text Available Introduction: Mesenchymal stem cells have immunomodulatory properties and own extensive potentials to proliferate and differentiate into different cell lineages. Thus, this study was conducted to investigate the effect of supernatant of rat MSCs on the neutrophils viability. Methods: MSCs was isolated from femoral and tibial bone marrow of rat (6-8 weeks and was cultured in DMEM. After maturation of MSCs, its supernatant was incubated with neutrophils isolated from peripheral blood of rat at 37 ° C for 1 h. Neutrophil survival was measured at 6 and 24 h incubation with supernatant of MSCs by flow cytometric analysis using An/PI. Data were analyzed by one-way ANOVA followed by Tukey test (P˂0.05. Results: 6-hour incubation of neutrophils with supernatant of MSCs significantly increased the healthy cells percentage and significantly decreased the amount of necrosis (P˂0.05, but no significant decrease was observed in regard with apoptosis compared to the controls (P˃0.05. The 24-hour incubation of neutrophils with cell supernatant significantly increased the percentage of healthy cells and apoptosis was significantly reduced compared to the control group (P˂0.05. Moreover, a reduction in cell necrosis was not significant in the treated groups compared to the control (P˃0.05. Conclusions: In addition to the clinical importance of MSCs, their biological aspects are of great potential for cell therapy, such as self-renewal, proliferation and immune modulatory effects.

Post-operative Wound Site Infection Caused by Nocardia species

Directory of Open Access Journals (Sweden)

Sunayana M. Jangla

2018-04-01

Full Text Available A61 year old diabetic female who was a known case of breast carcinoma and had undergone mastectomy was admitted with discharge from the post-operative wound site. Nocardia species was isolated from the discharge. She responded to treatment with trimethoprim-sulfamethoxazole.

Severe exercise and exercise training exert opposite effects on human neutrophil apoptosis via altering the redox status.

Directory of Open Access Journals (Sweden)

Guan-Da Syu

Full Text Available Neutrophil spontaneous apoptosis, a process crucial for immune regulation, is mainly controlled by alterations in reactive oxygen species (ROS and mitochondria integrity. Exercise has been proposed to be a physiological way to modulate immunity; while acute severe exercise (ASE usually impedes immunity, chronic moderate exercise (CME improves it. This study aimed to investigate whether and how ASE and CME oppositely regulate human neutrophil apoptosis. Thirteen sedentary young males underwent an initial ASE and were subsequently divided into exercise and control groups. The exercise group (n = 8 underwent 2 months of CME followed by 2 months of detraining. Additional ASE paradigms were performed at the end of each month. Neutrophils were isolated from blood specimens drawn at rest and immediately after each ASE for assaying neutrophil spontaneous apoptosis (annexin-V binding on the outer surface along with redox-related parameters and mitochondria-related parameters. Our results showed that i the initial ASE immediately increased the oxidative stress (cytosolic ROS and glutathione oxidation, and sequentially accelerated the reduction of mitochondrial membrane potential, the surface binding of annexin-V, and the generation of mitochondrial ROS; ii CME upregulated glutathione level, retarded spontaneous apoptosis and delayed mitochondria deterioration; iii most effects of CME were unchanged after detraining; and iv CME blocked ASE effects and this capability remained intact even after detraining. Furthermore, the ASE effects on neutrophil spontaneous apoptosis were mimicked by adding exogenous H(2O(2, but not by suppressing mitochondrial membrane potential. In conclusion, while ASE induced an oxidative state and resulted in acceleration of human neutrophil apoptosis, CME delayed neutrophil apoptosis by maintaining a reduced state for long periods of time even after detraining.

The effect of lidocaine on in vitro neutrophil and endothelial adhesion molecule expression induced by plasma obtained during tourniquet-induced ischaemia and reperfusion.

LENUS (Irish Health Repository)

Lan, W

2012-02-03

BACKGROUND: Changes in neutrophil and endothelial adhesion molecule expression occur during perioperative ischaemia and reperfusion (I\\/R) injury. We investigated the effects of lidocaine on neutrophil-independent changes in neutrophil and endothelial adhesion molecule expression associated with tourniquet-induced I\\/R. METHODS: Plasma was obtained from venous blood samples (tourniquet arm) taken before (baseline), during, 15 min, 2 and 24 h following tourniquet release in seven patients undergoing elective upper limb surgery with tourniquet application. Isolated neutrophils from healthy volunteers (n = 7) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1) for 1 h, and then incubated with I\\/R plasma for 2 h. Human umbilical vein endothelial cells (HUVECs) were pretreated in the presence or absence of lidocaine (0.005, 0.05 and 0.5 mg mL(-1)) for 1 h, and then incubated with the plasma for 4 h. Adhesion molecule expression was estimated using flow cytometry. Data were analysed using ANOVA and post hoc Student-Newman-Keuls tests. RESULTS: I\\/R plasma (withdrawn 15 min following tourniquet release) increased isolated neutrophil CD11b (P = 0.03), CD18 (P = 0.01) and endothelial intercellular adhesion molecule-1 (ICAM-1) (P = 0.008) expression compared to baseline. CD11b, CD18 and ICAM-1 expression on lidocaine (0.005 mg mL(-1)) treated neutrophils was similar to control. CD11b (P < 0.001), CD18 (P = 0.03) and ICAM-1 (P = 0.002) expression on lidocaine (0.05 mg mL(-1)) treated neutrophils and HUVECs was less than that on controls. CONCLUSION: Increased in vitro neutrophil and endothelial cell adhesion molecule expression on exposure to plasma obtained during the early reperfusion phase is diminished by lidocaine at greater than clinically relevant plasma concentrations.

File list: ALL.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Bld.20.AllAg.Neutrophils mm9 All antigens Blood Neutrophils SRX760584,SRX760581...,SRX760583,SRX760580,SRX801903,SRX760582 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Neutrophils.bed ...

File list: His.Bld.05.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.05.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956550,SRX956547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.05.AllAg.Neutrophils.bed ...

File list: ALL.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Bld.50.AllAg.Neutrophils mm9 All antigens Blood Neutrophils SRX760581,SRX760584...,SRX760583,SRX760580,SRX801903,SRX760582 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.50.AllAg.Neutrophils.bed ...

File list: His.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.10.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956550,SRX956547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.10.AllAg.Neutrophils.bed ...

File list: His.Bld.50.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.50.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956547,SRX956550 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.50.AllAg.Neutrophils.bed ...

Evidence for a self-enforcing inflammation in neutrophil-mediated chronic diseases

NARCIS (Netherlands)

Overbeek, S.A.

2011-01-01

In summary, this thesis provides evidence for the self-sustaining role of neutrophils in the inflammatory state in the pathogenesis of COPD and CD. In active disease, neutrophils release proteolytic enzymes that breakdown collagen. One of the collagen fragments can be neutrophilic chemoattractant

File list: His.Bld.20.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available His.Bld.20.AllAg.Neutrophils hg19 Histone Blood Neutrophils SRX956551,SRX956548,SRX...956545,SRX956544,SRX956547,SRX956550 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Bld.20.AllAg.Neutrophils.bed ...

Effects of ghrelin on the apoptosis of human neutrophils in vitro

Science.gov (United States)

Li, Bin; Zeng, Mian; Zheng, Haichong; Huang, Chunrong; He, Wanmei; Lu, Guifang; Li, Xia; Chen, Yanzhu; Xie, Ruijie

2016-01-01

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and the diffuse infiltration of neutrophils into the alveolar space. Neutrophils are abundant, short-lived leukocytes that play a key role in immune defense against microbial infections. These cells die via apoptosis following the activation and uptake of microbes, and will also enter apoptosis spontaneously at the end of their lifespan if they do not encounter pathogens. Apoptosis is essential for the removal of neutrophils from inflamed tissues and for the timely resolution of neutrophilic inflammation. Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue receptor, produced and secreted mainly from the stomach. Previous studies have reported that ghrelin exerts anti-inflammatory effects in lung injury through the regulation of the apoptosis of different cell types; however, the ability of ghrelin to regulate alveolar neutrophil apoptosis remains largely undefined. We hypothesized that ghrelin may have the ability to modulate neutrophil apoptosis. In this study, to examine this hypothesis, we investigated the effects of ghrelin on freshly isolated neutrophils in vitro. Our findings demonstrated a decrease in the apoptotic ratio (as shown by flow cytometry), as well as in the percentage of cells with decreased mitochondrial membrane potential (ΔΨm) and in the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling-positive rate, accompanied by an increased B-cell lymphoma 2/Bax ratio and the downregulation of cleaved caspase-3 in neutrophils following exposure to lipopolysaccharide (100 ng/ml). However, pre-treatment with ghrelin at a physiological level (100 nM) did not have a notable influence on the neutrophils in all the aforementioned tests. Our findings suggest that ghrelin may not possess the ability to modulate the neutrophil lifespan in vitro. PMID:27431014

Ascorbic acid supplementation diminishes microparticle elevations and neutrophil activation following SCUBA diving.

Science.gov (United States)

Yang, Ming; Barak, Otto F; Dujic, Zeljko; Madden, Dennis; Bhopale, Veena M; Bhullar, Jasjeet; Thom, Stephen R

2015-08-15

Predicated on evidence that diving-related microparticle generation is an oxidative stress response, this study investigated the role that oxygen plays in augmenting production of annexin V-positive microparticles associated with open-water SCUBA diving and whether elevations can be abrogated by ascorbic acid. Following a cross-over study design, 14 male subjects ingested placebo and 2-3 wk later ascorbic acid (2 g) daily for 6 days prior to performing either a 47-min dive to 18 m of sea water while breathing air (∼222 kPa N2/59 kPa O2) or breathing a mixture of 60% O2/balance N2 from a tight-fitting face mask at atmospheric pressure for 47 min (∼40 kPa N2/59 kPa O2). Within 30 min after the 18-m dive in the placebo group, neutrophil activation, and platelet-neutrophil interactions occurred, and the total number of microparticles, as well as subgroups bearing CD66b, CD41, CD31, CD142 proteins or nitrotyrosine, increased approximately twofold. No significant elevations occurred among divers after ingesting ascorbic acid, nor were elevations identified in either group after breathing 60% O2. Ascorbic acid had no significant effect on post-dive intravascular bubble production quantified by transthoracic echocardiography. We conclude that high-pressure nitrogen plays a key role in neutrophil and microparticle-associated changes with diving and that responses can be abrogated by dietary ascorbic acid supplementation. Copyright © 2015 the American Physiological Society.

Pre-operative use of anti-TNF-α agents and the risk of post-operative complications in patients with ulcerative colitis - a nationwide cohort study

DEFF Research Database (Denmark)

Nørgård, B M; Nielsen, J; Qvist, N

2012-01-01

It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC).......It is still controversial whether pre-operative anti-tumour necrosis factor-alpha (anti-TNF-α) agents increase post-operative complications in patients with ulcerative colitis (UC)....

Ex post power economic analysis of record of decision operational restrictions at Glen Canyon Dam.

Energy Technology Data Exchange (ETDEWEB)

Veselka, T. D.; Poch, L. A.; Palmer, C. S.; Loftin, S.; Osiek, B; Decision and Information Sciences; Western Area Power Administration

2010-07-31

On October 9, 1996, Bruce Babbitt, then-Secretary of the U.S. Department of the Interior signed the Record of Decision (ROD) on operating criteria for the Glen Canyon Dam (GCD). Criteria selected were based on the Modified Low Fluctuating Flow (MLFF) Alternative as described in the Operation of Glen Canyon Dam, Colorado River Storage Project, Arizona, Final Environmental Impact Statement (EIS) (Reclamation 1995). These restrictions reduced the operating flexibility of the hydroelectric power plant and therefore its economic value. The EIS provided impact information to support the ROD, including an analysis of operating criteria alternatives on power system economics. This ex post study reevaluates ROD power economic impacts and compares these results to the economic analysis performed prior (ex ante) to the ROD for the MLFF Alternative. On the basis of the methodology used in the ex ante analysis, anticipated annual economic impacts of the ROD were estimated to range from approximately $15.1 million to $44.2 million in terms of 1991 dollars ($1991). This ex post analysis incorporates historical events that took place between 1997 and 2005, including the evolution of power markets in the Western Electricity Coordinating Council as reflected in market prices for capacity and energy. Prompted by ROD operational restrictions, this analysis also incorporates a decision made by the Western Area Power Administration to modify commitments that it made to its customers. Simulated operations of GCD were based on the premise that hourly production patterns would maximize the economic value of the hydropower resource. On the basis of this assumption, it was estimated that economic impacts were on average $26.3 million in $1991, or $39 million in $2009.

Predictors of Post-Operative Pain Relief in Patients with Chronic Pancreatitis Undergoing the Frey or Whipple Procedure.

Science.gov (United States)

Sinha, Amitasha; Patel, Yuval A; Cruise, Michael; Matsukuma, Karen; Zaheer, Atif; Afghani, Elham; Yadav, Dhiraj; Makary, Martin A; Hirose, Kenzo; Andersen, Dana K; Singh, Vikesh K

2016-04-01

Post-operative pain relief in chronic pancreatitis (CP) is variable. Our objective was to determine clinical imaging or histopathologic predictor(s) of post-operative pain relief in CP patients undergoing the Whipple or Frey procedure. All patients who underwent a Whipple (n = 30) or Frey procedure (n = 30) for painful CP between January 2003 and September 2013 were evaluated. A toxic etiology was defined as a history of alcohol use and/or smoking. The pre-operative abdominal CT was evaluated for calcification(s) and main pancreatic duct (MPD) dilation (≥5 mm). The post-operative histopathology was evaluated for severe fibrosis. Clinical imaging and histopathologic features were evaluated as predictors of post-operative pain relief using univariable and multivariable regression analysis. A total of 60 patients (age 51.6 years, 53% males) were included in our study, of whom 42 (70%) reported post-operative pain relief over a mean follow-up of 1.1 years. There were 37 (62%) patients with toxic etiology, 36 (60%) each with calcification(s) and MPD dilation. A toxic etiology, calcifications, and severe fibrosis were associated with post-operative pain relief on univariable analysis (all p Whipple or Frey procedure.

The effect of dietary fatty acids on post-operative inflammatory response in a porcine model

DEFF Research Database (Denmark)

Langerhuus, Sine Nygaard; Jensen, Karin Hjelholt; Tønnesen, Else Kirstine

2012-01-01

), sunflower oil (SO, n 28), or animal fat (AF, n 28) was evaluated with respect to post-operative responses in inflammatory markers in a porcine model on aortic vascular prosthetic graft infection. In the early post-operative period (0 necrosis factor...

The LRRC8A Mediated “Swell Activated” Chloride Conductance Is Dispensable for Vacuolar Homeostasis in Neutrophils

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Philippe Behe

2017-05-01

Full Text Available The dialysis of human and mouse neutrophils in patch clamp experiments in the conventional whole-cell mode induces the emergence of a chloride (Cl- current that appeared to be primarily regulated by cytoplasmic ionic strength. The characteristics of this current resembled that of the classical, and ubiquitous volume-sensitive outwardly rectifying Cl- current: strong outward rectification, selectivity sequence of the Eisenman1 type, insensitivity to external pH and strong inhibition by tamoxifen, DCPIB and WW781. We show that this current is essentially supported by the leucine rich repeat containing 8 A (LRRC8A; the naturally occurring LRRC8A truncation mutant in ebo/ebo mice drastically reduced Cl- conductance in neutrophils. Remarkably, the residual component presents a distinct pharmacology, but appears equally potentiated by reduced ionic strength. We have investigated the role of the LRRC8A-supported current in the ionic homeostasis of the phagosomal compartment. The vacuolar pH, measured using SNARF-1 labeled Candida albicans, normally rises because of NADPH oxidase activity, and this elevation is blocked by certain Cl- channel inhibitors. However, the pH rise remains intact in neutrophils from the ebo/ebo mice which also demonstrate preserved phagocytic and respiratory burst capacities and normal-sized vacuoles. Thus, the LRRC8A-dependent conductance of neutrophils largely accounts for their “swell activated” Cl- current, but is not required for homeostasis of the phagosomal killing compartment.

Regulation of calcium homeostasis in activated human neutrophils ...

African Journals Online (AJOL)

Objectives. The objectives of the current study were to: (i) present an integrated model for the restoration of calcium homeostasis in activated human neutrophils based on current knowledge and recent research; and (ii) identify potential targets for the modulation of calcium fluxes in activated neutrophils based on this model ...

Identification of glutathione adducts of α-chlorofatty aldehydes produced in activated neutrophils.

Science.gov (United States)

Duerr, Mark A; Aurora, Rajeev; Ford, David A

2015-05-01

α-Chlorofatty aldehydes (α-ClFALDs) are produced by hypochlorous acid targeting plasmalogens during neutrophil activation. This study investigated the reaction of the α-chlorinated carbon of α-ClFALD with the nucleophile, GSH. Utilizing ESI/MS/MS, the reaction product of GSH and the 16-carbon α-ClFALD, 2-chlorohexadecanal (2-ClHDA), was characterized. The resulting conjugate of 2-ClHDA and GSH (HDA-GSH) has an intact free aldehyde, and the chlorine at the α-carbon is ejected. Stable isotope-labeled [d4]HDA-GSH was synthesized, which further confirmed the structure, and was used to quantify natural α-ClFALD conjugates of GSH (FALD-GSH) using reverse-phase LC with detection by ESI/MS/MS using selected reaction monitoring. HDA-GSH is elevated in RAW 264.7 cells treated with physiologically relevant concentrations of exogenous 2-ClHDA. Furthermore, PMA-treated primary human neutrophils have elevated levels of HDA-GSH and the conjugate of 2-chlorooctadecanal (2-ClODA) and GSH (ODA-GSH), as well as elevated levels of 2-ClHDA and 2-ClODA. Production of both conjugates in PMA-stimulated neutrophils was reduced by 3-aminotriazole pretreatment, which also blocks endogenous α-ClFALD production. Additionally, plasma FALD-GSH levels were elevated in the K/BxN mouse arthritis model. Taken together, these studies demonstrate novel peptidoaldehydes derived from GSH and α-ClFALD in activated human neutrophils and in vivo in K/BxN mice. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

Nutritional status, nutrition practices and post-operative complications in patients with gastrointestinal cancer.

Science.gov (United States)

Garth, A K; Newsome, C M; Simmance, N; Crowe, T C

2010-08-01

Malnutrition and its associated complications are a considerable issue for surgical patients with upper gastrointestinal and colorectal cancer. The present study aimed to determine whether specific perioperative nutritional practices and protocols are associated with improved patient outcomes in this group. Patients admitted for elective upper gastrointestinal or colorectal cancer surgery (n = 95) over a 19-month period underwent a medical history audit assessing weight changes, nutritional intake, biochemistry, post-operative complications and length of stay. A subset of patients (n = 25) underwent nutritional assessment by subjective global assessment prior to surgery in addition to assessment of post-operative medical outcomes, nutritional intake and timing of dietetic intervention. Mean (SD) length of stay for patients was 14.0 (12.2) days, with complication rates at 35%. Length of stay was significantly longer in patients who experienced significant preoperative weight loss compared to those who did not [17.0 (15.8) days versus 10.0 (6.8) days, respectively; P nutritional assessment, 32% were classified as mild-moderately malnourished and 16% severely malnourished. Malnourished patients were hospitalised twice as long as well-nourished patients [15.8 (12.8) days versus 7.6 (3.5) days; P nutrition post surgery was a factor in post-operative outcomes, with a positive correlation with length of stay (r = 0.493; P cancer. Poor nutritional status coupled with delayed and inadequate post-operative nutrition practices are associated with worse clinical outcomes.

The effect of aprotinin on hypoxia-reoxygenation-induced changes in neutrophil and endothelial function.

LENUS (Irish Health Repository)

Harmon, D

2012-02-03

BACKGROUND AND OBJECTIVE: An acute inflammatory response associated with cerebral ischaemia-reperfusion contributes to the development of brain injury. Aprotinin has potential, though unexplained, neuroprotective effects in patients undergoing cardiac surgery. METHODS: Human neutrophil CD11 b\\/CD18, endothelial cell intercellular adhesion molecule-1 (ICAM-1) expression and endothelial interleukin (IL)-1beta supernatant concentrations in response to in vitro hypoxia-reoxygenation was studied in the presence or absence of aprotinin (1600 KIU mL(-1)). Adhesion molecule expression was quantified using flow cytometry and IL-1beta concentrations by enzyme-linked immunosorbent assay. Data were analysed using ANOVA and post hoc Student-Newman-Keuls test as appropriate. RESULTS: Exposure to 60-min hypoxia increased neutrophil CD11b expression compared to normoxia (170+\\/-46% vs. 91+\\/-27%, P = 0.001) (percent intensity of fluorescence compared to time 0) (n = 8). Hypoxia (60 min) produced greater upregulation of CD11b expression in controls compared to aprotinin-treated neutrophils [(170+\\/-46% vs. 129+\\/-40%) (P = 0.04)] (n = 8). Hypoxia-reoxygenation increased endothelial cell ICAM-1 expression (155+\\/-3.7 vs. 43+\\/-21 mean channel fluorescence, P = 0.0003) and IL-1beta supernatant concentrations compared to normoxia (3.4+\\/-0.4 vs. 2.6+\\/-0.2, P = 0.02) (n = 3). Hypoxia-reoxygenation produced greater upregulation of ICAM- 1 expression [(155+\\/-3.3 vs. 116+\\/-0.7) (P = 0.001)] and IL-1beta supernatant concentrations [(3.4+\\/-0.3 vs. 2.6+\\/-0.1) (P = 0.01)] in controls compared to aprotinin-treated endothelial cell preparation (n = 3). CONCLUSIONS: Hypoxia-reoxygenation-induced upregulation of neutrophil CD11b, endothelial cell ICAM-1 expression and IL-1beta concentrations is decreased by aprotinin at clinically relevant concentrations.

Production of extracellular traps against Aspergillus fumigatus in vitro and in infected lung tissue is dependent on invading neutrophils and influenced by hydrophobin RodA.

Directory of Open Access Journals (Sweden)

Sandra Bruns

2010-04-01

Full Text Available Aspergillus fumigatus is the most important airborne fungal pathogen causing life-threatening infections in immunocompromised patients. Macrophages and neutrophils are known to kill conidia, whereas hyphae are killed mainly by neutrophils. Since hyphae are too large to be engulfed, neutrophils possess an array of extracellular killing mechanisms including the formation of neutrophil extracellular traps (NETs consisting of nuclear DNA decorated with fungicidal proteins. However, until now NET formation in response to A. fumigatus has only been demonstrated in vitro, the importance of neutrophils for their production in vivo is unclear and the molecular mechanisms of the fungus to defend against NET formation are unknown. Here, we show that human neutrophils produce NETs in vitro when encountering A. fumigatus. In time-lapse movies NET production was a highly dynamic process which, however, was only exhibited by a sub-population of cells. NETosis was maximal against hyphae, but reduced against resting and swollen conidia. In a newly developed mouse model we could then demonstrate the existence and measure the kinetics of NET formation in vivo by 2-photon microscopy of Aspergillus-infected lungs. We also observed the enormous dynamics of neutrophils within the lung and their ability to interact with and phagocytose fungal elements in situ. Furthermore, systemic neutrophil depletion in mice almost completely inhibited NET formation in lungs, thus directly linking the immigration of neutrophils with NET formation in vivo. By using fungal mutants and purified proteins we demonstrate that hydrophobin RodA, a surface protein making conidia immunologically inert, led to reduced NET formation of neutrophils encountering Aspergillus fungal elements. NET-dependent killing of Aspergillus-hyphae could be demonstrated at later time-points, but was only moderate. Thus, these data establish that NET formation occurs in vivo during host defence against A

Predictors of Post-operative Mycetoma Recurrence Using Machine-Learning Algorithms: The Mycetoma Research Center Experience.

Directory of Open Access Journals (Sweden)

Ali Wadal

2016-10-01

surgical excision. Patients with disease duration [5-10] years, with pedal mycetoma, had previous surgery, with no family history but presented with a disease size (> 10 cm, were non- farmers and underwent wide local surgical excision. Other groups are patients with disease duration (≤5 years, with pedal mycetoma, age 10 cm, working as farmers or students and underwent wide local surgical excision. In conclusion, these groups of patients need special care to reduce the incidence of post-operative recurrence with its morbidity and detrimental consequences. In depth studies for the other predisposing factors for post-operative recurrence such as genetic, immunological and environmental factors are needed.

File list: ALL.Bld.10.AllAg.Neutrophils [Chip-atlas[Archive

Lifescience Database Archive (English)

Full Text Available ALL.Bld.10.AllAg.Neutrophils hg19 All antigens Blood Neutrophils SRX956551,SRX95654...8,SRX956545,SRX956544,SRX956550,SRX956552,SRX956549,SRX956546,SRX956547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Bld.10.AllAg.Neutrophils.bed ...

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults

Science.gov (United States)

Shepherd, Sam O.; Wilson, Oliver J.; Adlan, Ahmed M.; Wagenmakers, Anton J. M.; Shaw, Christopher S.; Lord, Janet M.

2017-01-01

Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on immune function in sedentary adults. Twenty-seven (43 ± 11 years) healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate) or MICT (70% maximum heart rate) group training program. Aerobic capacity (VO2peak), neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function. PMID:28656073

Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults

Directory of Open Access Journals (Sweden)

David B. Bartlett

2017-01-01

Full Text Available Neutrophils and monocytes are key components of the innate immune system that undergo age-associated declines in function. This study compared the impact of high-intensity interval training (HIIT and moderate-intensity continuous training (MICT on immune function in sedentary adults. Twenty-seven (43 ± 11 years healthy sedentary adults were randomized into ten weeks of either a HIIT (>90% maximum heart rate or MICT (70% maximum heart rate group training program. Aerobic capacity (VO2peak, neutrophil and monocyte bacterial phagocytosis and oxidative burst, cell surface receptor expression, and systemic inflammation were measured before and after the training. Total exercise time commitment was 57% less for HIIT compared to that for MICT while both significantly improved VO2peak similarly. Neutrophil phagocytosis and oxidative burst and monocyte phagocytosis and percentage of monocytes producing an oxidative burst were improved by training similarly in both groups. Expression of monocyte but not neutrophil CD16, TLR2, and TLR4 was reduced by training similarly in both groups. No differences in systemic inflammation were observed for training; however, leptin was reduced in the MICT group only. With similar immune-enhancing effects for HIIT compared to those for MICT at 50% of the time commitment, our results support HIIT as a time efficient exercise option to improve neutrophil and monocyte function.

Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy.

Science.gov (United States)

Maas, Rutger Jh; van den Brand, Jan Ajg; Waanders, Femke; Meijer, Esther; Goor van, Harry; Peters, Hilde P; Hofstra, Julia M; Wetzels, Jack Fm

2016-01-01

Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of ≥135 µmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria 50% reduction from baseline. Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome. Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value

Assessment of 99Tcm-ethylenedicysteine diuretic renography in pre-and post-operative pediatric congenital hydronephrosis

International Nuclear Information System (INIS)

Ye Zhiyi; Wang Hui; Li Jianing; Fu Hongliang; Wu Jingchuan

2010-01-01

Objective: To investigate the clinical value of 99 Tc m -ethylenedicysteine (EC) diuretic renography (DR) in pre-and post-operative pediatric congenital hydronephrosis. Methods: The DR with injection of Furosemide at 15 min of forty children with hydronephrosis was retrospectively studied. The preoperative renal blood perfusion rate (BPR), effective renal plasma flow (ERPF), grade of hydronephrosis,renogram and renal dynamic imaging of pre- and post-operative kidneys were compared. The t-test and Mann-Whitney test were used for data analysis. Results: (1) Of 40 pathological kidneys, the BPR increased 5.99% (t=-5.13, P<0.01) from pre-operative to post-operative: (34.05 ± 11.07)% to (40.04 ± 8.56)%. The ERPF increased 12.48 ml/min (t=-4.35, P<0.01) from pre-operative to post-operative: (57.81 ± 34.32) ml/min to (70.29 ± 5.37) ml/min. (2) The grade of hydronephrosis of 40 pathological kidneys improved significantly(Z=-2.64, P<0.01) with the mean sum of ranks of 47.21 pre-operatively to 33.79 post-operatively.(3) As the hydronephrosis worsened, the collecting system became bigger, the renal parenchyma became thinner, the extent of intrarenal parenchymal photopenia became larger and the response to diuretic challenge in pathological kidneys decreased or became totally irresponsive. (4)Thirty-seven cases of obstruction at ureteropelvic junction (UPJO) and 3 cases at ureterovesical junction (UVJO) were diagnosed by DR, which were all confirmed by surgery. Conclusions: DR is a reliable method to evaluate pediatric congenital hydronephrosis.It can accurately reflect the grade and (or) severity of the disease, guide therapy and assess the therapeutic success of operation. (authors)

Long-term biatrial recordings in post-operative atrial fibrillation.

Science.gov (United States)

Masè, M; Graffigna, A; Sinelli, S; Pallaoro, G; Nollo, G; Ravelli, F

2010-01-01

Although atrial fibrillation (AF) is a common complication of cardiac surgery, its pathophysiology remains unclear. The study of post-operative AF demands for the recording of cardiac electrical activity in correspondence of AF onset and progression. Long-term recordings in post-surgery patients could provide this information, but, to date, have been limited to surface signals, which precludes a characterization of the arrhythmic triggers and substrate. In this study we demonstrate the feasibility of a continuous long-term recording of atrial electrical activities from the right and left atria in post-surgery patients. Local atrial epicardial electrograms are acquired by positioning temporary pacing wires in the right and left atria at the end of the intervention, while three day recordings are obtained by a digital holter recorder, adapted to epicardial signal features. The capability of the system to map local atrial activity and the possibility to obtain quantitative information on atrial rate and synchronization from the processed epicardial signals are proven in representative examples. The quantitative description of local atrial properties opens new perspective in the investigation of post-surgery AF.

Frequency of post-operative faecal incontinence in patients with closed and open internal anal sphincterotomy

International Nuclear Information System (INIS)

Ghayas, N.G.; Younus, S.M.; Mirani, A.J.; Ghayasuddin, M.

2015-01-01

Fissure in ano is one of the commonest benign and painful proctologic diseases causing considerable morbidity and reduction in quality of life. There are medical as well as surgical treatment options for anal fissure. The study was conducted to compare the frequency of postoperative faecal incontinence in patients with closed lateral internal anal sphincterotomy with von-greaves knife versus standard Parks operation (open method) for chronic anal fissure. Methods: This was a randomized controlled trial (RCT) was conducted at the Department of Surgery, KVSS, S.I.T.E. Hospital, Karachi, for a period of six months from 13th February to 12th August 2011. Ninety four consecutive patients having chronic anal fissure were assigned through blocked randomization to groups A and B, with 47 patients in each group. Closed lateral internal anal sphincterotomy (CLIAS) via von-greaves knife was carried out in patients of group-A whereas patients of group-B were subjected to open internal anal sphincterotomy (OIAS) also known as Parks procedure. Faecal incontinence was noted on the 5th post-operative day. Data was analysed using SPSS 16. Results: There were 81 (86.2%) males and 13 (13.8%) females with male to female ratio being 6:1. Mean age was 38.38 mp±14.56 years. Post-operative faecal incontinence in patients undergoing CLIAS was 4.3% while it was 21.3% in those undergoing OIAS with a p-value of 0.027. CLIAS with von-greaves knife is effective in reducing faecal incontinence on 5th postoperative day as compared to standard OIAS. Conclusion: CLIAS with von-greaves knife is effective in reducing faecal incontinence on 5th postoperative day as compared to OIAS (Park's procedure). Therefore, this technique may be used in future regularly to treat chronic anal fissure for prevention of this morbidity. (author)

Failure of rabbit neutrophils to secrete endogenous pyrogen when stimulated with staphylococci.

Science.gov (United States)

Hanson, D F; Murphy, P A; Windle, B E

1980-06-01

Cells obtained from acute peritoneal exudates in rabbits were separated into neutrophil and mononuclear populations by centrifugation on colloidal silica gradients. When these populations were separately incubated in tissue culture medium in the presence of opsonized Staphylococcus epidermidis, endogenous pyrogen was secreted only by the adherent cells of the mononuclear population. Pyrogen production by neutrophils could not have amounted to as much as 1% of the pyrogen produced by macrophages. When mononuclear cells were added back to purified neutrophils, no pyrogen was produced that could not be accounted for by the number of macrophages added. Rabbit blood cells were similarly fractionated on colloidal silica gradients. Again, endogenous pyrogen was made only by the adherent mononuclear population. The neutrophils isolated on these gradients appeared to be morphologically normal and were 85% viable as judged by dye exclusion. They showed normal random motility. Both blood and exudate neutrophils responded chemotactically to N-formyl Met-Leu-Phe, and blood neutrophils responded chemotactically to zymosan-activated serum. Both kinds of neutrophils phagocytosed zymosan particles and both killed opsonized S. epidermidis in a roller tube system. Both blood and exudate neutrophils showed normal superoxide production when stimulated with opsonized zymosan particles. This evidence suggests that macrophages are the only source of endogenous pyrogens, and that pyrogens secreted by cell populations that are rich in neutrophils are to be attributed to the monocytes or macrophages that they contain.

Assessment of post-operative pain management among acutely and electively admitted patients - a Swedish ward perspective.

Science.gov (United States)

Magidy, Mahnaz; Warrén-Stomberg, Margareta; Bjerså, Kristofer

2016-04-01

Swedish health care is regulated to involve the patient in every intervention process. In the area of post-operative pain, it is therefore important to evaluate patient experience of the quality of pain management. Previous research has focused on mapping this area but not on comparing experiences between acutely and electively admitted patients. Hence, the aim of this study was to investigate the experiences of post-operative pain management quality among acutely and electively admitted patients at a Swedish surgical department performing soft-tissue surgery. A survey study design was used as a method based on a multidimensional instrument to assess post-operative pain management: Strategic and Clinical Quality Indicators in Postoperative Pain Management (SCQIPP). Consecutive patients at all wards of a university hospital's surgical department were included. Data collection was performed at hospital discharge. In total, 160 patients participated, of whom 40 patients were acutely admitted. A significant difference between acutely and electively admitted patients was observed in the SCQIPP area of environment, whereas acute patients rated the post-operative pain management quality lower compared with those who were electively admitted. There may be a need for improvement in the areas of post-operative pain management in Sweden, both specifically and generally. There may also be a difference in the experience of post-operative pain quality between acutely and electively admitted patients in this study, specifically in the area of environment. In addition, low levels of the perceived quality of post-operative pain management among the patients were consistent, but satisfaction with analgesic treatment was rated as good. © 2015 John Wiley & Sons, Ltd.

Post-operative symptoms at home in children following day case ...

African Journals Online (AJOL)

Adele

of the parents did not know enough about the treatment of the wound and of the overall ... Post operative symptoms following elective day case surgery are amenable to treatment and ..... with inguinal and abdominal wall hernias in children.

Neutrophil CD64 has a high negative predictive value for exclusion ...

African Journals Online (AJOL)

[13] Multiple studies agree that neutrophil CD64 has high diagnostic speci city and sensitivity.[13,18-20] In the light of the above information, we prospectively evaluated the usefulness of neutrophil CD64 expression in diagnosing neonatal infection. e main objective of the study was quantitation of neutrophil. CD64 by ow ...

Neutrophil targeted nano-drug delivery system for chronic obstructive lung diseases.

Science.gov (United States)

Vij, Neeraj; Min, Taehong; Bodas, Manish; Gorde, Aakruti; Roy, Indrajit

2016-11-01

The success of drug delivery to target airway cell(s) remains a significant challenge due to the limited ability of nanoparticle (NP) systems to circumvent protective airway-defense mechanisms. The size, density, surface and physical-chemical properties of nanoparticles are the key features that determine their ability to navigate across the airway-barrier. We evaluated here the efficacy of a PEGylated immuno-conjugated PLGA-nanoparticle (PINP) to overcome this challenge and selectively deliver drug to specific inflammatory cells (neutrophils). We first characterized the size, shape, surface-properties and neutrophil targeting using dynamic laser scattering, transmission electron microscopy and flow cytometry. Next, we assessed the efficacy of neutrophil-targeted PINPs in transporting through the airway followed by specific binding and release of drug to neutrophils. Finally, our results demonstrate the efficacy of PINP mediated non-steroidal anti-inflammatory drug-(ibuprofen) delivery to neutrophils in murine models of obstructive lung diseases, based on its ability to control neutrophilic-inflammation and resulting lung disease. Copyright © 2016 Elsevier Inc. All rights reserved.

The role of phagocytosis, oxidative burst and neutrophil extracellular traps in the interaction between neutrophils and the periodontal pathogen Porphyromonas gingivalis.

Science.gov (United States)

Jayaprakash, K; Demirel, I; Khalaf, H; Bengtsson, T

2015-10-01

Neutrophils are regarded as the sentinel cells of innate immunity and are found in abundance within the gingival crevice. Discovery of neutrophil extracellular traps (NETs) within the gingival pockets prompted us to probe the nature of the interactions of neutrophils with the prominent periopathogen Porphyromonas gingivalis. Some of the noted virulence factors of this Gram-negative anaerobe are gingipains: arginine gingipains (RgpA/B) and lysine gingipain (Kgp). The aim of this study was to evaluate the role of gingipains in phagocytosis, formation of reactive oxygen species, NETs and CXCL8 modulation by using wild-type strains and isogenic gingipain mutants. Confocal imaging showed that gingipain mutants K1A (Kgp) and E8 (RgpA/B) induced extracellular traps in neutrophils, whereas ATCC33277 and W50 were phagocytosed. The viability of both ATCC33277 and W50 dwindled as the result of phagocytosis and could be salvaged by cytochalasin D, and the bacteria released high levels of lipopolysaccharide in the culture supernatant. Porphyromonas gingivalis induced reactive oxygen species and CXCL8 with the most prominent effect being that of the wild-type strain ATCC33277, whereas the other wild-type strain W50 was less effective. Quantitative real-time polymerase chain reaction revealed a significant CXCL8 expression by E8. All the tested P. gingivalis strains increased cytosolic free calcium. In conclusion, phagocytosis is the primary neutrophil response to P. gingivalis, although NETs could play an accessory role in infection control. Although gingipains do not seem to directly regulate phagocytosis, NETs or oxidative burst in neutrophils, their proteolytic properties could modulate the subsequent outcomes such as nutrition acquisition and survival by the bacteria. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Protein cross-linking by chlorinated polyamines and transglutamylation stabilizes neutrophil extracellular traps.

Science.gov (United States)

Csomós, Krisztián; Kristóf, Endre; Jakob, Bernadett; Csomós, István; Kovács, György; Rotem, Omri; Hodrea, Judit; Bagoly, Zsuzsa; Muszbek, Laszlo; Balajthy, Zoltán; Csősz, Éva; Fésüs, László

2016-08-11

Neutrophil extracellular trap (NET) ejected from activated dying neutrophils is a highly ordered structure of DNA and selected proteins capable to eliminate pathogenic microorganisms. Biochemical determinants of the non-randomly formed stable NETs have not been revealed so far. Studying the formation of human NETs we have observed that polyamines were incorporated into the NET. Inhibition of myeloperoxidase, which is essential for NET formation and can generate reactive chlorinated polyamines through hypochlorous acid, decreased polyamine incorporation. Addition of exogenous primary amines that similarly to polyamines inhibit reactions catalyzed by the protein cross-linker transglutaminases (TGases) has similar effect. Proteomic analysis of the highly reproducible pattern of NET components revealed cross-linking of NET proteins through chlorinated polyamines and ɛ(γ-glutamyl)lysine as well as bis-γ-glutamyl polyamine bonds catalyzed by the TGases detected in neutrophils. Competitive inhibition of protein cross-linking by monoamines disturbed the cross-linking pattern of NET proteins, which resulted in the loss of the ordered structure of the NET and significantly reduced capacity to trap bacteria. Our findings provide explanation of how NETs are formed in a reproducible and ordered manner to efficiently neutralize microorganisms at the first defense line of the innate immune system.

Diverse novel functions of neutrophils in immunity, inflammation, and beyond

OpenAIRE

Mocsai, A.

2013-01-01

Neutrophils have long been considered simple suicide killers at the bottom of the hierarchy of the immune response. That view began to change 10–20 yr ago, when the sophisticated mechanisms behind how neutrophils locate and eliminate pathogens and regulate immunity and inflammation were discovered. The last few years witnessed a new wave of discoveries about additional novel and unexpected functions of these cells. Neutrophils have been proposed to participate in protection against intracellu...

Thoracoscopic pulmonary wedge resection without post-operative chest drain

DEFF Research Database (Denmark)

Holbek, Bo Laksafoss; Hansen, Henrik Jessen; Kehlet, Henrik

2016-01-01

%) patients had a pneumothorax of mean size 12 ± 12 mm on supine 8-h post-operative X-ray for which the majority resolved spontaneously within 2-week control. There were no complications on 30-day follow-up. Median length of stay was 1 day. CONCLUSIONS: The results support that VATS wedge resection...

Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

Directory of Open Access Journals (Sweden)

Liling Yang

2017-10-01

Full Text Available Background/Aims: Forsythia suspensa Vahl. (Oleaceae fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN, the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF

Lactose Induces Phenotypic and Functional Changes of Neutrophils and Macrophages to Alleviate Acute Pancreatitis in Mice

Directory of Open Access Journals (Sweden)

Li-Long Pan

2018-04-01

Full Text Available Acute pancreatitis (AP is one common clinical acute abdominal disease, for which specific pharmacological or nutritional therapies remain elusive. Lactose, a macronutrient and an inducer of host innate immune responses, possesses immune modulatory functions. The current study aimed to investigate potential modulatory effects of lactose and the interplay between the nutrient and pancreatic immunity during experimentally induced AP in mice. We found that either prophylactic or therapeutic treatment of lactose time-dependently reduced the severity of AP, as evidenced by reduced pancreatic edema, serum amylase levels, and pancreatic myeloperoxidase activities, as well as by histological examination of pancreatic damage. Overall, lactose promoted a regulatory cytokine milieu in the pancreas and reduced infiltration of inflammatory neutrophils and macrophages. On acinar cells, lactose was able to suppress caerulein-induced inflammatory signaling pathways and to suppress chemoattractant tumor necrosis factor (TNF-α and monocyte chemotactic protein-1 production. Additionally, lactose acted on pancreas-infiltrated macrophages, increasing interleukin-10 and decreasing tumor necrosis factor alpha production. Notably, lactose treatment reversed AP-associated infiltration of activated neutrophils. Last, the effect of lactose on neutrophil infiltration was mimicked by a galectin-3 antagonist, suggesting a potential endogenous target of lactose. Together, the current study demonstrates an immune regulatory effect of lactose to alleviate AP and suggests its potential as a convenient, value-added therapeutic macronutrient to control AP, and lower the risk of its systemic complications.

New strategies for maintaining post-seismic operations of lifeline corridors.

Science.gov (United States)

2014-10-01

This project furthered the development of three strategies that could positively impact maintaining post-seismic operations of lifeline corridors. In Year 1, most of the focus : was on the development of the three individual strategies. In Year 2, a ...

The Neutrophil-Platelet Score (NPS Predicts Survival in Primary Operable Colorectal Cancer and a Variety of Common Cancers.

Directory of Open Access Journals (Sweden)

David G Watt

Full Text Available Recent in-vitro studies have suggested that a critical checkpoint early in the inflammatory process involves the interaction between neutrophils and platelets. This confirms the importance of the innate immune system in the elaboration of the systemic inflammatory response. The aim of the present study was to examine whether a combination of the neutrophil and platelet counts were predictive of survival in patients with cancer.Patients with histologically proven colorectal cancer who underwent potentially curative resection at a single centre between March 1999 and May 2013 (n = 796 and patients with cancer from the Glasgow Inflammation Outcome Study, who had a blood sample taken between January 2000 and December 2007 (n = 9649 were included in the analysis.In the colorectal cancer cohort, there were 173 cancer and 135 non-cancer deaths. In patients undergoing elective surgery, cancer-specific survival (CSS at 5 years ranged from 97% in patients with TNM I disease and NPS = 0 to 57% in patients with TNM III disease and NPS = 2 (p = 0.019 and in patients undergoing elective surgery for node-negative colon cancer from 98% (TNM I, NPS = 0 to 65% (TNM II, NPS = 2 (p = 0.004. In those with a variety of common cancers there were 5218 cancer and 929 non-cancer deaths. On multivariate analysis, adjusting for age and sex and stratified by tumour site, incremental increase in the NPS was significantly associated with poorer CSS (p<0.001.The neutrophil-platelet score predicted survival in a variety of common cancers and highlights the importance of the innate immune system in patients with cancer.

Inhalation of activated protein C inhibits endotoxin-induced pulmonary inflammation in mice independent of neutrophil recruitment

NARCIS (Netherlands)

Slofstra, S. H.; Groot, A. P.; Maris, N. A.; Reitsma, P. H.; Cate, H. Ten; Spek, C. A.

2006-01-01

BACKGROUND AND PURPOSE: Intravenous administration of recombinant human activated protein C (rhAPC) is known to reduce lipopolysaccharide (LPS)-induced pulmonary inflammation by attenuating neutrophil chemotaxis towards the alveolar compartment. Ideally, one would administer rhAPC in pulmonary

Effect of the Raga Ananda Bhairavi in Post Operative Pain Relief Management.

Science.gov (United States)

Kumar, Thirumurthy Sathish; Muthuraman, M; Krishnakumar, R

2014-10-01

Music is considered as an universal language and has influences the human existence at various levels.In recent years music therapy has evolved as a challenge of research with a clinical approach involving science and art. Music therapy has been used for various therapeutic reasons like Alzheimer's disease,Hypertension and mental disorders to name a few. We conducted a study to establish the effect of the classical ragam Anandhabhairavi on post operative pain relief. A randomized controlled study involving 60 patients who were to undergo surgery was conducted at PSG Institute of Medical Sciences and Research,Coimbatore.30 patients selected at random and were exposed to the ragam Anandhabhairavi which was played in their room pre operatively (from the day they got admitted for surgery) and 3 days post operatively. The control group did not listen to the music during their stay in the hospital. An observation chart was attached in which the requirement of analgesics by the patient was recorded. On completion of the study and on analysis,the ragam Anandhabhairavi had a significant effect in post operative pain management which was evidenced by the reduction in analgesic requirement by 50 % in those who listened to the ragam.A significant p value of <0.001 was obtained.

A review of recent advances in data analytics for post-operative patient deterioration detection.

Science.gov (United States)

Petit, Clemence; Bezemer, Rick; Atallah, Louis

2018-06-01

Most deaths occurring due to a surgical intervention happen postoperatively rather than during surgery. The current standard of care in many hospitals cannot fully cope with detecting and addressing post-surgical deterioration in time. For millions of patients, this deterioration is left unnoticed, leading to increased mortality and morbidity. Postoperative deterioration detection currently relies on general scores that are not fully able to cater for the complex post-operative physiology of surgical patients. In the last decade however, advanced risk and warning scoring techniques have started to show encouraging results in terms of using the large amount of data available peri-operatively to improve postoperative deterioration detection. Relevant literature has been carefully surveyed to provide a summary of the most promising approaches as well as how they have been deployed in the perioperative domain. This work also aims to highlight the opportunities that lie in personalizing the models developed for patient deterioration for these particular post-surgical patients and make the output more actionable. The integration of pre- and intra-operative data, e.g. comorbidities, vitals, lab data, and information about the procedure performed, in post-operative early warning algorithms would lead to more contextualized, personalized, and adaptive patient modelling. This, combined with careful integration in the clinical workflow, would result in improved clinical decision support and better post-surgical care outcomes.

The effect of lipocortin 1 on neutrophil deformability

Directory of Open Access Journals (Sweden)

E. M. Drost

1996-01-01

Full Text Available Lipocortn 1 (Lc1 is an anti-inflammatory protein, which, given systemically, inhibits polymorphonuclear neutrophil (PMN emigration from the circulation to sites of inflammation; delivery of Lc1 to the inflamed site is ineffective. We have examined the effect of Lc1 on changes in PMN deformability, and observed a consistent improvement in the deformability of unstimulated PMN; N-formyl-methionyl-leucyl-phenylalanine (fMLP-activated cell deformability was unaltered. A Lc1-induced increase in cell deformability may reduce PMN sequestration so contributing to the anti-migratory effects of systemic Lc1 previously demonstrated in vivo.

Induction of hyperresponsiveness in human airway tissue by neutrophils--mechanism of action.

Science.gov (United States)

Anticevich, S Z; Hughes, J M; Black, J L; Armour, C L

1996-05-01

The two main features of asthma are bronchial hyperresponsiveness and inflammation. The inflammatory response in asthma consists of infiltration and activation of a variety of inflammatory cells including neutrophils. Our previous studies have shown that stimulated neutrophil supernatants cause hyperresponsiveness of human bronchial tissue in vitro. To investigate the effect of the sensitization status of the tissue and the albumin concentration used to prepare supernatants on the response of human bronchial tissue to stimulated neutrophil supernatants. Neutrophil supernatants were prepared from human isolated blood in the presence of varying concentrations of albumin (0%, 0.1% and 4%). Neutrophil supernatants were added to sensitized and non-sensitized human isolated bronchial tissue which was stimulated with electrical field stimulation (EFS) (20 s every 4 min). Receptor antagonists specific for the prostaglandin and thromboxane (10(-7) M GR32191), platelet activating factor (10(-6) M WEB 2086), leukotriene D4 (10(-6) M MK-679) and neurokinin A (10(-7) M SR48968) receptors were used to identify neutrophil products responsible for the effects observed in the bronchial tissue. In non-sensitized human bronchial tissue, stimulated neutrophil supernatants induced a direct contraction in the presence of 0% and 0.1% but not 4% albumin. This contraction was due to leukotriene D4 as MK-679 completely inhibited the contraction. In contrast, stimulated neutrophil supernatants increased responsiveness of sensitized human bronchial tissue to EFS. The increased responsiveness was observed only in the presence of 0.1% albumin, with the site of modulation likely to be prejunctional on the parasympathetic nerve. The increased responsiveness was not inhibited by any of the antagonists tested. Sensitization status of the tissue and albumin concentration effect the responsiveness of human bronchial tissue to stimulated neutrophil supernatant. Our results suggest a possible role for

Role of avastin on the incidence of post-operative vitreous hemorrhage after vitrectomy in diabetic vitreous hemorrhage

International Nuclear Information System (INIS)

Ahmed, N.; Shaheer, M.; Tahir, M.Y.

2014-01-01

Diabetic retinopathy is one of the most common cause of legal blindness. Five to 10% of diabetic patients suffer from the proliferative diabetic retinopathy which includes the formation of new vessels on the retina and optic disc which can be complicated as vitreous hemorrhage and tractional retinal detachment. Pars plana vitrectomy along with laser photocoagulation is being used for the management of vitreous hemorrhage. In our study we used injection avastin one week before surgery to see its role on the incidence of rebleed after vitrectomy in diabetic vitreous hemorrhage. Materials and Methods; Fifty patients were divided into 2 equal groups on the basis of simple random sampling. 25 patients in Group I were operated with routine pars plana vitrectomy with endolaser photo- coagulation while in Group II all the 25 patients were given injection avastin intra-vitreally one week before surgery. Evaluation was done on the first post operative day, first follow up visit (one week) and after one month to see the incidence of re-bleed. Chi-square test was used for statistical analysis. Results: Fifty patients divided into two groups. In Group I, 3 patients had recurrent vitreous hemorrhage on first post-operative day, 3 patients had re-bleed on first follow up visit, and only 2 patients had re-bleed after one month. In Group II, none of the patients had recurrent vitreous hemorrhage on first post-operative day and on first follow-up visit (one week) while 2 patients had re-bleed after one month. Conclusion: Injection intravitreal Avastin (Bevaci- zumab) one week before surgery significantly reduces the risk of vitreous hemorrhage after vitrectomy in diabetic patients. (author)

Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

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Sébastien Lenglet

2014-01-01

Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

Rac1 deletion in mouse neutrophils has selective effects on neutrophil functions

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Glogauer, Michael; Marchal, Christophe C.; Zhu, Fei; Worku, Aelaf; Clausen, Björn E.; Foerster, Irmgard; Marks, Peter; Downey, Gregory P.; Dinauer, Mary; Kwiatkowski, David J.

2003-01-01

Defects in myeloid cell function in Rac2 knockout mice underline the importance of this isoform in activation of NADPH oxidase and cell motility. However, the specific role of Rac1 in neutrophil function has been difficult to assess since deletion of Rac1 results in embryonic lethality in mice. To

Neutrophil evasion strategies by Streptococcus pneumoniae and Staphylococcus aureus.

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Lewis, Megan L; Surewaard, Bas G J

2018-03-01

Humans are well equipped to defend themselves against bacteria. The innate immune system employs diverse mechanisms to recognize, control and initiate a response that can destroy millions of different microbes. Microbes that evade the sophisticated innate immune system are able to escape detection and could become pathogens. The pathogens Streptococcus pneumoniae and Staphylococcus aureus are particularly successful due to the development of a wide variety of virulence strategies for bacterial pathogenesis and they invest significant efforts towards mechanisms that allow for neutrophil evasion. Neutrophils are a primary cellular defense and can rapidly kill invading microbes, which is an indispensable function for maintaining host health. This review compares the key features of Streptococcus pneumoniae and Staphylococcus aureus in epidemiology, with a specific focus on virulence mechanisms utilized to evade neutrophils in bacterial pathogenesis. It is important to understand the complex interactions between pathogenic bacteria and neutrophils so that we can disrupt the ability of pathogens to cause disease.

Effects of acrolein on leukotriene biosynthesis in human neutrophils.

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Berry, Karin A Zemski; Henson, Peter M; Murphy, Robert C

2008-12-01

Acrolein is a toxic, highly reactive alpha,beta-unsaturated aldehyde that is present in high concentrations in cigarette smoke. In the current study, the effect of acrolein on eicosanoid synthesis in stimulated human neutrophils was examined. Eicosanoid synthesis in neutrophils was initiated by priming with granulocyte-macrophage colony-stimulating factor (GM-CSF) and subsequent stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP) and 5-lipoxygenase (5-LO) products in addition to small amounts of cyclooxygenase (COX) products were detected using LC/MS/MS. A dose-dependent decrease in the formation of 5-LO products was observed in GM-CSF/fMLP-stimulated neutrophils when acrolein (0-50 microM) was present with almost complete inhibition at > or = 25 microM acrolein. The production of COX products was not affected by acrolein in these cells. The effect of acrolein was examined on key parts of the eicosanoid pathway, such as arachidonic acid release, intracellular calcium ion concentration, and adenosine production. In addition, the direct effect of acrolein on 5-LO enzymatic activity was probed using a recombinant enzyme. Some of these factors were affected by acrolein but did not completely explain the almost complete inhibition of 5-LO product formation in GM-CSF/fMLP-treated cells with acrolein. In addition, the effect of acrolein on different stimuli that initiate the 5-LO pathway [platelet-activating factor (PAF)/fMLP, GM-CSF/PAF, opsonized zymosan, and A23187] was examined. Acrolein had no significant effect on the leukotriene production in neutrophils stimulated with PAF/fMLP, GM-CSF/ PAF, or OPZ. Additionally, 50% inhibition of the 5-LO pathway was observed in A23187-stimulated neutrophils. Our results suggest that acrolein has a profound effect on the 5-LO pathway in neutrophils, which may have implications in disease states, such as chronic obstructive pulmonary disease and other pulmonary disease, where both activated neutrophils and acrolein are

Influence of exogenous leptin on redox homeostasis in neutrophils and lymphocytes cultured in synovial fluid isolated from patients with rheumatoid arthritis

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Michał Gajewski

2016-07-01

Full Text Available Objectives : Leptin is an adipose cells derived hormone that regulates energy homeostasis within the body. Energy metabolism of immune cells influences their activity within numerous pathological states, but the effect of leptin on these cells in unclear. On the one hand, it was observed that leptin induces neutrophils chemotaxis and modulates phagocytosis. On the other hand, neutrophils exposed to leptin did not display detectable Ca 2+ ions mobilization or β 2 -integrin upregulation. In this study, we investigated the effect of leptin on the redox homeostasis in lymphocytes and neutrophils. Material and methods : Neutrophils and lymphocytes were isolated by density-gradient centrifugation of blood from healthy volunteers. Cells were cultured with or without leptin (100 ng/ml for lymphocytes and 500 ng/ml for neutrophils or with or without synovial fluid (85% for 0–72 h. Culture media were not changed during incubation. Cells were homogenized and homogenate was frozen until laboratory measurements. Redox homeostasis was assessed by the reduced glutathione (GSH vs. oxidized glutathione (GSSG ratio and membrane lipid peroxidation evaluation. Results : Lymphocytes cultured with leptin and synovial fluid showed a significant increase of the GSSG level. The GSSG/GSH ratio increased by 184 ±37%. In neutrophils incubated in a similar environment, the GSSG/GSH ratio increased by just 21 ±7%, and the effect was observed irrespectively of whether they were exposed to leptin or synovial fluid or both together. Neither leptin nor synovial fluid influenced lipid peroxidation in neutrophils, but in lymphocytes leptin intensified lipid peroxidation. Conclusions : Leptin altered the lymphocytes, but not neutrophils redox state. Because firstly neutrophils are anaerobic cells and have just a few mitochondria and secondly lymphocytes have typical aerobic metabolism, the divergence of our data supports the hypothesis that leptin induces oxidative stress by

The galactose-binding lectin isolated from Bauhinia bauhinioides Mart seeds inhibits neutrophil rolling and adhesion via primary cytokines.

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Girão, Deysen Kerlla Fernandes Bezerra; Cavada, Benildo Sousa; de Freitas Pires, Alana; Martins, Timna Varela; Franco, Álvaro Xavier; Morais, Cecília Mendes; Santiago do Nascimento, Kyria; Delatorre, Plinio; da Silva, Helton Colares; Nagano, Celso Shiniti; Assreuy, Ana Maria Sampaio; Soares, Pedro Marcos Gomes

2015-05-01

In this study, the amino acid sequence and anti-inflammatory effect of Bauhinia bauhinioides (BBL) lectin were evaluated. Tandem mass spectrometry revealed that BBL possesses 86 amino acid residues. BBL (1 mg/kg) intravenously injected in rats 30 min prior to inflammatory stimuli inhibited the cellular edema induced by carrageenan in only the second phase (21% - 3 h, 19% - 4 h) and did not alter the osmotic edema induced by dextran. BBL also inhibited carrageenan peritoneal neutrophil migration (51%), leukocyte rolling (58%) and adhesion (68%) and the neutrophil migration induced by TNF-α (64%). These effects were reversed by the association of BBL with galactose, demonstrating that the carbohydrate-binding domain is essential for lectin activity. In addition, BBL reduced myeloperoxidase activity (84%) and TNF-α (68%) and IL1-β (47%) levels. In conclusion, the present investigation demonstrated that BBL contains highly homologous isolectins, resulting in a total of 86 amino acid residues, and exhibits anti-inflammatory activity by inhibiting neutrophil migration by reducing TNF-α and IL1-β levels via the lectin domain. Copyright © 2015 John Wiley & Sons, Ltd.

Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis

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Ong, Catherine W. M.; Elkington, Paul T.; Brilha, Sara; Ugarte-Gil, Cesar; Tome-Esteban, Maite T.; Tezera, Liku B.; Pabisiak, Przemyslaw J.; Moores, Rachel C.; Sathyamoorthy, Tarangini; Patel, Vimal; Gilman, Robert H.; Porter, Joanna C.; Friedland, Jon S.

2015-01-01

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease. PMID:25996154

Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.

Science.gov (United States)

Ong, Catherine W M; Elkington, Paul T; Brilha, Sara; Ugarte-Gil, Cesar; Tome-Esteban, Maite T; Tezera, Liku B; Pabisiak, Przemyslaw J; Moores, Rachel C; Sathyamoorthy, Tarangini; Patel, Vimal; Gilman, Robert H; Porter, Joanna C; Friedland, Jon S

2015-05-01

Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.

Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma

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Wang D

2013-03-01

Full Text Available Dan Wang, Jia-Xin Yang, Dong-Yan Cao, Xi-Run Wan, Feng-Zhi Feng, Hui-Fang Huang, Keng Shen, Yang Xiang Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China Background: The purpose of this study was to evaluate the relationship between preoperative inflammatory markers (neutrophil-lymphocyte ratio and platelet-lymphocyte ratio and cervical stromal involvement in patients with endometrioid adenocarcinoma. Methods: We studied 318 patients with endometrioid adenocarcinoma who underwent comprehensive surgical staging. We used univariate and multivariate analyses of cervical stromal involvement and receiver-operating curves to calculate optimal cutoff values for neutrophil-lymphocyte and platelet-lymphocyte ratios to predict cervical stromal involvement. Results: The presence of cervical stromal involvement was associated with neutrophil-lymphocyte ratio and platelet-lymphocyte ratio (P = 0.009 and P = 0.031, respectively. Multivariate analysis showed that higher neutrophil-lymphocyte and platelet-lymphocyte ratios independently predicted cervical stromal involvement (odds ratio 3.10, 95% confidence interval 1.10–8.76, P = 0.032, and odds ratio 5.27, 95% confidence interval 1.94–14.35, P = 0.001, respectively. At a threshold of 2.01, the neutrophil-lymphocyte ratio was 71.0% sensitive and 63.8% specific for stromal involvement; at a 172.24 threshold, the platelet-lymphocyte ratio was 48.4% sensitive and 88.9% specific. Conclusion: Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios can help identify the risk of cervical stromal involvement in patients with endometrial cancer. Evaluating these ratios may help select patients who should be particularly watched and tested for cervical stromal involvement. Keywords: neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, endometrioid adenocarcinoma

The emerging role of neutrophils in thrombosis – The journey of TF through NETs

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Konstantinos eKambas

2012-12-01

Full Text Available The production of TF by neutrophils and their contribution in thrombosis was until recently a matter of scientific debate. Experimental data suggested the de novo TF production by neutrophils under inflammatory stimuli, while others proposed that these cells acquired microparticle-derived TF. Recent experimental evidence revealed the critical role of neutrophils in thrombotic events. Neutrophil derived TF has been implicated in this process in several human and animal models. Additionally, neutrophil extracellular trap (NET release has emerged as a major contributor in neutrophil-driven thrombogenicity in disease models including sepsis, deep venous thrombosis and malignancy. It is suggested that NETs provide the scaffold for fibrin deposition and platelet entrapment and subsequent activation. The recently reported autophagy-dependent extracellular delivery of TF in NETs further supports the involvement of neutrophils in thrombosis. Herein, we seek to review novel data regarding the role of neutrophils in thrombosis, emphasizing the implication of TF and NETs.

Iodinated contrast media induce neutrophil apoptosis through a mitochondrial and caspase mediated pathway.