Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

[Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients (French translation of the article)]. / Comparaison intra-individuelle de la dilatation pupillaire par une solution intracamérulaire standardisée combinée de mydriatiques (Mydrane®) en peropératoire versus un insert ophtalmique (Mydriasert®) en préopératoire dans la chirurgie de la cataracte standard de patients non diabétiques.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: In total, 111 eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Same-eye comparison of pupillary dilation with an intraoperative standardized intracameral combination of mydriatics (Mydrane®) versus a preoperative ophthalmic (Mydriasert®) in standard cataract surgery in non-diabetic patients.

INTRODUCTION: Cataract surgery is the most commonly performed surgery in the world, and its success depends in part on the quality of mydriasis. PURPOSE: To compare, for the same eye, the pupillary dilation obtained with Mydrane® (standardized intracameral solution of 0.02% tropicamide, combined with 0.31% phenylephrine and 1% lidocaine) intraoperatively versus Mydriasert® (0.28mg tropicamide insert and 5.4mg phenylephrine) with a contact time between 45 and 60 minutes in the preoperative period. METHODS: Single center prospective study from November 2016 to January 2018 at the Laveran Army Instructional Hospital in Marseille. Patients referred for surgery were dilated at the preoperative consultation with Mydriasert®. The pupillary diameter after 45-60 minutes of contact with the insert was manually measured, by two different examiners, through the "iris image" tab of the Pentacam® elevation topography. Patients were dilated on the day of their cataract surgery with 0.2cc of Mydrane® injected in the anterior chamber through a paracentesis. Thirty seconds later, prior to injection of viscoelastic, an eye photograph was taken by screen capture. The pupillary diameter was evaluated by two different examiners with to the Piximeter 5.9 metrology software. The difference in pupil dilation between Mydriasert® and Mydrane® was tested with the paired series Student t-test. RESULTS: A hundred and eleven eyes of 82 patients were included. Mydriasert® achieved a mean pupillary dilation of 7.21±0.79mm. The mydriasis obtained with Mydrane® averaged 6.35±0.8mm. This difference of 0.86mm was statistically significant (P<0.001) with a confidence interval of 95% [-0.97; -0.74]. CONCLUSION: On average, Mydrane® dilates the pupil less than Mydriasert®. However, the mydriasis obtained with Mydrane® remains comfortable for the performance of the capsulorhexis. It helps save preoperative time and affords additional anesthetic to the cataract surgery. Nevertheless, the use of Mydriasert® is beneficial when extra mydriasis is required.

Intergenerational and early life influences on the well-being of Australian Aboriginal and Torres Strait Islander children: overview and selected findings from Footprints in Time, the Longitudinal Study of Indigenous Children.

Footprints in Time: The Longitudinal Study of Indigenous Children (LSIC) is a national study of 1759 Australian Aboriginal and Torres Strait Islander children living across urban, regional and remote areas of Australia. The study is in its 11th wave of annual data collection, having collected extensive data on topics including birth and early life influences, parental health and well-being, identity, cultural engagement, language use, housing, racism, school engagement and academic achievement, and social and emotional well-being. The current paper reviews a selection of major findings from Footprints in Time relating to the developmental origins of health and disease for Australian Aboriginal and Torres Strait Islander peoples. Opportunities for new researchers to conduct further research utilizing the LSIC data set are also presented.

Cassava flour slurry as a low-cost alternative to commercially available gel for obstetrical ultrasound: a blinded non-inferiority trial comparison of image quality.

OBJECTIVE: To evaluate the quality of ultrasound images obtained with cassava flour slurry (CFS) compared with conventional gel in order to determine objectively whether CFS could be a true low-cost alternative. DESIGN: Blinded non-inferiority trial. SETTING: Obstetrical ultrasound unit in an academic medical centre. POPULATION OR SAMPLE: Women with a singleton pregnancy, undergoing anatomy ultrasounds. METHODS: Thirty pregnant women had standard biometry measures obtained with CFS and conventional gel. Images were compared side-by-side in random order by two blinded sonologists and rated for image resolution, detail and total image quality using a 10-cm visual analogue scale. Ratings were compared using paired t-tests. Participant and sonographer experience was measured using five-point Likert scales. MAIN OUTCOME MEASURES: Image resolution, detail, and total image quality. Participant experience of gel regarding irritation, messiness, and ease of removal. RESULTS: We found no significant difference between perceived image quality obtained with CFS (mean = 6.2, SD = 1.2) and commercial gel (mean = 6.4, SD = 1.2) [t (28) = -1.1; P = 0.3]. Images were not rated significantly differently for either reviewer in any measure, any standardized image or any view of a specific anatomic structure. All five sonographers rated CFS as easy to obtain clear images and easy for patient and machine cleanup. Only one participant reported itching with CFS. CONCLUSIONS: CFS produces comparable image quality to commercial ultrasound gel. The dissemination of these results and the simple CFS recipe could significantly increase access to ultrasound for screening, monitoring and diagnostic purposes in resource-limited settings. FUNDING: This study was internally funded by our department. TWEETABLE ABSTRACT: Low-cost homemade cassava flour slurry creates images equal to commercial ultrasound gel, improving access.

Nocardia nova sphenoid sinusitis and infratemporal fossa abscess.

INTRODUCTION: Nocardia sinusitis is exceptional, as a Medline search revealed only one published case. The authors report a case of sphenoid sinusitis complicated by infratemporal fossa abscess, which raised several diagnostic problems. CASE REPORT: The patient was referred with temporal headache, subacute trigeminal neuralgia and subsequent infectious syndrome. Computed tomography imaging revealed left sphenoid sinusitis with osteolysis and infratemporal fossa abscess, as well as suspicious lung nodules suggestive of the initial site of infection. Bacteriological specimens obtained by endoscopic sphenoidotomy confirmed the presence of Nocardia nova. A favourable outcome was observed in response to targeted antibiotic therapy. DISCUSSION AND CONCLUSION: Sphenoid sinusitis with infratemporal fossa abscess is an exceptional mode of presentation of nocardiosis, illustrating the polymorphic clinical features of this disease. Bacteriological examination of samples taken directly from the organ concerned, in this case, by sphenoidotomy, is the only formal diagnostic criterion. Antibiotic therapy with intravenous imipenem/amikacin, followed by oral sulfamethoxazole/trimethoprim (Bactrim Forte(®)) for several months, is the key to successful management.

Utilisation of focused assessment with sonography for trauma (fast) in a referral hospital in an acute conflict zone

Introduction The role of Focused Assessment with Sonography for Trauma (FAST) is well described in the literature in high-resource general emergency care settings. However; there are limited data on utilisation of FAST by local providers in limited-resource conflict settings. We describe the first experience of a hospital in E-DRC using the FAST exam in triage to evaluate and expedite blunt and penetrating trauma patients during an armed invasion. Methods HEAL Africa Hospital (HEAL) is a tertiary trauma centre located in Goma; Eastern Democratic Republic of Congo. In 2010; ultrasound training was initiated. During subsequent armed fighting and the invasion of Goma; the hospital adopted the FAST exam as triage tool in the emergency centre (EC). Ultrasound scans were prospectively logged and perceived utility for immediate patient management was recorded. At a 1 year follow-up; a cohort of physician and nurses considered downstream patient recipients were also asked perceived utility towards its use. Results 222/243 (91) of ultrasound scans were recorded by physicians as having positive utility for immediate patient management. 61/243 (25) scans were FAST exams; 24 for obstetric evaluation and 158 were scans for pain management with ultrasound regional anaesthesia. 23/61 (41) of the FAST were reported as positive. Patients with + FAST were immediately prioritised and either a chest tube was placed or taken to the operating room for laparotomy. All 23 patients brought for laparotomy or chest tube were shown to have haemoperitoneum or positive output respectively. Discussion : The introduction of FAST training and requisite equipment in resource stressed healthcare settings is both desirable and feasible. In this study; the introduction of FAST by local providers had an important influence on the decision making process and enabled immediate triage of casualties to laparotomy; chest tube or clinical observations. Prospective controlled research is further needed to evaluate the impact

Pelvic fracture-related urethral and bladder injury.

Major pelvic ring fracture (PRF) due to blunt trauma results in lower urinary tract injury (LUTI) in up to 10% of cases. Significant comorbidity may result and this is particularly the case for unrecognised injury. The increase in military injuries due to improvised explosive devices in recent conflicts has revealed a complex injury cohort. The incidence of pelvic fracture related LUTI in these casualties is up to three times higher than that seen in civilian patients with pelvic fracture. A complete understanding of LUTI following pelvic fracture is still lacking. Complex fractures of the anterior pelvic arch are associated with LUTI and initial management is largely conservative. In battlefield injuries, the combination of the blast wave, penetrating fragment and bodily displacement results in open pelvic fracture combined with gross perineal and pelvic soft-tissue destruction and traumatic femoral amputations. These are some of the most challenging injuries that any surgical team will manage and life saving measures are the priority. There are established pathways for the management of LUTI following blunt trauma related pelvic fracture. Military injuries are more complex and require a significantly different approach. This paper outlines the developments in the understanding and management of pelvic fracture-related LUTI, focussing primarily on injury mechanisms and early management. Recent military surgical experience is discussed, highlighting the significant differences to civilian practice.

Amputación por accidente botrópico grave: reporte de un caso / Amputation bothropic serious accident: a case report

RESUMEN:Se denomina accidente bothrópico al cuadro clínico producido por el veneno inoculado por ofidios del género Bothrops(Yarará). Este se caracteriza por ser proteolítico, coagulante y hemorragíparo, y ocasiona en las víctimasefectos locales y sistémicos.Las complicaciones incluyen: tendinitis, fascitis, infección bacteriana, abscesos y síndrome compartimental. Esteúltimo tiene una incidencia inferior...(AU)

SUMMARY:Clinical simptoms produced by venom of Bothrops (Yarará) are called ophidism. The poison of these snakes hasproteolitic, coagulant action and causes hemorrage. It causes local and systemic effects.Complications include: tendinitis, fasciitis, bacterial infection, abscesses and compartment syndrome...(AU)

Chama-se acidente botr´ ao quadro clínico produzidos pelo veneno de Bothrops ophidia. Recaracteriza por ser proteolítica,coagulante e hemorragiparo e causas das vítimas em efeitos locais e sistÛmicos. No sítio da inoculaþÒo ocorreum dano tecidual imediatamente com mionecrose, hemorragia e edema.Complicaþ§es incluem: tendinite, fasciíte plantar, infecþÒo bacteriana, abscesso, e síndrome compartimental...(AU)

Amputación por accidente botrópico grave: reporte de un caso / Amputation bothropic serious accident: a case report

RESUMEN:Se denomina accidente bothrópico al cuadro clínico producido por el veneno inoculado por ofidios del género Bothrops(Yarará). Este se caracteriza por ser proteolítico, coagulante y hemorragíparo, y ocasiona en las víctimasefectos locales y sistémicos.Las complicaciones incluyen: tendinitis, fascitis, infección bacteriana, abscesos y síndrome compartimental. Esteúltimo tiene una incidencia inferior...

SUMMARY:Clinical simptoms produced by venom of Bothrops (Yarará) are called ophidism. The poison of these snakes hasproteolitic, coagulant action and causes hemorrage. It causes local and systemic effects.Complications include: tendinitis, fasciitis, bacterial infection, abscesses and compartment syndrome...

Chama-se acidente botrï ao quadro clínico produzidos pelo veneno de Bothrops ophidia. Recaracteriza por ser proteolítica,coagulante e hemorragiparo e causas das vítimas em efeitos locais e sistêmicos. No sítio da inoculação ocorreum dano tecidual imediatamente com mionecrose, hemorragia e edema.Complicações incluem: tendinite, fasciíte plantar, infecção bacteriana, abscesso, e síndrome compartimental...

Mechanical and optical dynamic model of lung.

A multiscale, multiphysics model generates synthetic images of alveolar compression under spherical indentation at the visceral pleura of an inflated lung. A mechanical model connects the millimeter scale of an indenter tip to the behavior of alveoli, walls, and membrane at the micrometer scale. A finite-difference model of optical coherence tomography (OCT) generates the resulting images. Results show good agreement with the experiments performed using a unique indenter-OCT system. The images depict the physical result with the addition of refractive artifacts and speckle. Compression of the alveoli alters the refractive effects, which introduce systematic errors in the computation of alveolar volume. The complete computational model is useful to evaluate new proposed imaging instrumentation and to develop algorithms for obtaining quantitative data on deformation. Among the potential applications, a better understanding of recruitment of alveoli during inflation of a lung, obtained through a combination of models and imaging could lead to improvements in noninvasive treatment of atelectasis.

Global Government Health Partners' Forum 2006: eighteen months later.

BACKGROUND: The challenge of global health worker shortages, particularly among nurses, has been the topic of numerous forums over the last several years. Nevertheless, there has been little attention given to the roles of government chief nursing and medical officers as key partners in addressing health worker shortages. This partnership and its potential impact on the adequacy of the global health workforce was the focus of the most recent Global Government Health Partners (GGHP) Forum held in November 2006 in Atlanta, Georgia, USA. This forum was uniquely designed to create a context for government chief nursing officers and chief medical officers to engage in a joint learning and planning experience focused on positioning their leadership to impact health workforce issues. AIM: This article describes an 18-month follow-up evaluation of the outcomes of the GGHP. The purpose of the evaluation was to assess the impact of the forum experience on the actions of participants based on the country-level plans they produced at the forum. This important feedback is intended to inform the design of future partnered global forums and gain insights into the utility of forum-based action plans. The evaluation process itself has served as an opportunity for the engagement of university faculty, students and staff in a global service learning experience. CONCLUSION: The outcomes of this evaluation indicate that important progress has been made by countries whose leadership was involved in the forum, and was also an important learning activity for those participating in the conduct of the study.

Enhancement of inflammatory mediator release by beta(2)-adrenoceptor agonists in airway epithelial cells is reversed by glucocorticoid action.

BACKGROUND AND PURPOSE: Due to their potent bronchodilator properties, beta(2)-adrenoceptor agonists are a mainstay of therapy in asthma. However, the effects of beta(2)-adrenoceptor agonists on inflammation are less clear. Accordingly, we have investigated the effects of beta(2)-adrenoceptor agonists on inflammatory mediator release. EXPERIMENTAL APPROACH: Transcription factor activation, and both release and mRNA expression of IL-6 and IL-8 were examined by luciferase reporter assay, elisa and real-time RT-PCR in bronchial human epithelial BEAS-2B cells or primary human bronchial epithelial cells grown at an air-liquid interface. KEY RESULTS: Pre-incubation with beta(2)-adrenoceptor agonists (salbutamol, salmeterol, formoterol) augmented the release and mRNA expression of IL-6 and IL-8 induced by IL-1beta and IL-1beta plus histamine, whereas NF-kappaB-dependent transcription was significantly repressed, and AP-1-dependent transcription was unaffected. These effects were mimicked by other cAMP-elevating agents (PGE(2), forskolin). Enhancement of cytokine release by beta(2)-adrenoceptor agonists also occurred in primary bronchial epithelial cells. Addition of dexamethasone with salmeterol repressed IL-6 and IL-8 release to levels that were similar to the repression achieved in the absence of salmeterol. IL-6 release was enhanced when salmeterol was added before, concurrently or after IL-1beta plus histamine stimulation, whereas IL-8 release was only enhanced by salmeterol addition prior to stimulation. CONCLUSIONS AND IMPLICATIONS: Enhancement of IL-6 and IL-8 release may contribute to the deleterious effects of beta(2)-adrenoceptor agonists in asthma. As increased inflammatory mediator expression is prevented by the addition of glucocorticoid to the beta(2)-adrenoceptor, our data provide further mechanistic support for the use of combination therapies in asthma management.

Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury.

Spinal release of cytokines may play a critical role in the maladapted nociceptive signaling underlying chronic pain states. In order to investigate this biology, we have developed a novel 'high flux' intrathecal microdialysis approach in combination with multiplex bead-based immunoassay technology to concurrently monitor the spinal release of interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)alpha in rats with unilateral sciatic nerve chronic constriction injury (CCI). Intrathecal microdialysis was performed under isoflurane/N(2)O anaesthesia in rats with confirmed mechanical hypersensitivity. In a first study, C-fiber strength electrical stimulation of the operated nerve in neuropathic rats was found to evoke a dramatic increase in IL-1beta efflux ( approximately 15-fold) that was significantly greater than that observed in the sham-operated group. Spinal IL-6 efflux was also responsive to primary afferent stimulation, whereas TNFalpha was not. In a second study, treatment with the glial inhibitor propentofylline for 7days normalized CCI-induced mechanical hypersensitivity. In the same animals, this treatment also significantly reduced intrathecal IL-1beta, IL-6 and TNFalpha and prevented afferent stimulation-evoked cytokine release of both IL-1beta and IL-6. These results provide support for glia as the source of the majority of intrathecal IL-1beta, IL-6 and TNFalpha that accompanies mechanical hypersensitivity in the CCI rat. Moreover, our studies demonstrate the ability of a neurone-glia signaling mechanism to dynamically modulate this release and support a role of spinal IL-1beta in the phasic transmission of abnormal pain signals.

In situ stress testing to identify Australian black tiger prawns (Penaeus monodon) free of gill-associated virus and Mourilyan virus.

OBJECTIVE: To identify whether black tiger prawns (Penaeus monodon) in the Weipa region of the Gulf of Carpentaria, Queensland, are free of gill-associated virus (GAV) and Mourilyan virus (MoV), which are endemic in P. monodon along the east coast of Queensland. PROCEDURE: Preliminary screening suggested that Weipa might be a source of P. monodon that are free of GAV and MoV. To assess this, more than 150 prawns captured near Weipa were maintained locally in tanks for 2 weeks and bled three times as a stressor to promote higher-level infections. The existence of GAV and MoV in lymphoid organ tissue was then determined using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Some prawns were maintained in tanks for an additional 75 days before being tested. RESULTS: Real-time qRT-PCR did not detect GAV in any of 33 pools of RNA isolated from the 166 prawns tested. MoV was detected in five pools of RNA at extremely low viral RNA copy numbers close to the sensitivity threshold of the test. MoV was also detected at a similar low copy number in one of nine pearl-oyster mantle samples used as negative controls. CONCLUSIONS: GAV infection is either absent or, like MoV, potentially present at a very low prevalence in juvenile P. monodon inhabiting the inshore waters at Weipa. This region can thus be recommended as a good source of P. monodon certifiable as specific pathogen-free for GAV and MoV, which is desirable for domestication and selective breeding programs in Australia.

Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid.

OBJECTIVES: Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF. METHODS: Human peripheral blood and SF neutrophils were incubated with iron-free lactoferrin and apoptosis determined after 9 h. SF from patients with RA was added to isolated neutrophils, with or without immunodepletion of lactoferrin, and effects on neutrophil apoptosis determined. Levels of lactoferrin in SF were assessed and related to disease duration and markers of disease activity. RESULTS: Iron-free lactoferrin significantly delayed apoptosis of peripheral blood neutrophils, in a concentration-dependent manner after 9 h in culture (P < 0.04). Lactoferrin could also delay apoptosis of neutrophils isolated from SF of patients with RA. SF from patients with established RA delayed apoptosis of peripheral blood neutrophils and this effect was significantly reduced by depletion of lactoferrin (P < 0.03). Lactoferrin levels in SF from patients with established RA did not correlate with disease severity, but did correlate with markers of inflammation (CRP) and with the presence of RF. SF from patients with arthritis of <12 weeks duration did not contain significant levels of lactoferrin. CONCLUSION: Lactoferrin contributes to extended neutrophil survival in the rheumatoid joint in the established phase of RA but not in very early arthritis.

A role for the integrin alpha6beta1 in the differential distribution of CD4 and CD8 T-cell subsets within the rheumatoid synovium.

OBJECTIVE: CD4 and CD8 T-cell subsets accumulate in distinct microdomains within the inflamed rheumatoid synovium. The molecular basis for their differential distribution remains unclear. Since chemokines and adhesion molecules play an important role in the positioning of leucocytes at sites of inflammation, we tested the hypothesis that the differential expression and function of chemokine and/or adhesion molecules explains why CD4(+) T cells accumulate within perivascular cuffs, whereas CD8(+) T cells distribute diffusely within the tissue. METHODS: Expression of an extensive panel of chemokine receptors and adhesion molecules on matched CD4(+) and CD8(+) T cells from peripheral blood (PB) and synovial fluid (SF) was analysed by multicolour flow cytometry. Migration assays and flow-based adhesion assays were used to assess the functional consequences of any differences in the expression of chemokine and adhesion receptors. RESULTS: CD4(+) and CD8(+) T cells from PB and SF expressed unique yet consistent patterns of chemokine and adhesion receptors. SF CD8(+) T cells were much less promiscuous in their expression of chemokine receptors than SF CD4(+) T cells. The alpha(6)beta(1) integrin was highly expressed on PB CD4(+) T cells, but not on PB CD8(+) T cells. Laminin, the ligand for alpha(6)beta(1), retained CD4(+) T cells, but less so CD8(+) T cells, within inflamed synovial tissue. CONCLUSION: Infiltrating PB CD4(+) T cells, but not CD8(+) T cells, express functional levels of the alpha(6)beta(1) integrin. We propose that this leads to their retention within the rheumatoid synovium in perivascular cuffs, which are defined and delineated by the expression of laminin.

Ozone inhalation induces exacerbation of eosinophilic airway inflammation and hyperresponsiveness in allergen-sensitized mice.

BACKGROUND: Ozone (O(3)) exposure evokes asthma exacerbations by mechanisms that are poorly understood. We used a murine model to characterize the effects of O(3) on allergic airway inflammation and hyperresponsiveness and to identify factors that might contribute to the O(3)-induced exacerbation of asthma. METHODS: BALB/c mice were sensitized and challenged with Aspergillus fumigatus (Af). A group of sensitized and challenged mice was exposed to 3.0 ppm of O(3) for 2 h and studied 12 h later (96 h after Af challenge). Naive mice and mice exposed to O(3) alone were used as controls. Bronchoalveolar lavage (BAL) cellular and cytokine content, lung function [enhanced pause (P(enh))], isometric force generation by tracheal rings and gene and protein expression of Fas and FasL were assessed. Apoptosis of eosinophils was quantified by FACS. RESULTS: In sensitized mice allergen challenge induced a significant increase of P(enh) and contractile force in tracheal rings that peaked 24 h after challenge and resolved by 96 h. O(3) inhalation induced an exacerbation of airway hyperresponsiveness accompanied by recurrence of neutrophils and enhancement of eosinophils 96 h after allergen challenge. The combination of allergen and O(3) exposure inhibited Fas and FasL gene and protein expression and eosinophil apoptosis and increased interleukin-5 (IL-5), granulocyte-macrophage-colony stimulating factor (GM-CSF) and G-CSF protein levels. CONCLUSIONS: O(3) affects airway responsiveness of allergen-primed airways indirectly by increasing viability of eosinophils and eosinophil-mediated pathological changes.

Fibroblasts as novel therapeutic targets in chronic inflammation.

A characteristic feature of many chronic inflammatory diseases is their persistence and predilection for certain sites. The molecular basis for such tissue tropism and failure of the inflammatory response to resolve has until relative recently remained obscure. Recent studies have strongly implicated fibroblasts as cells which contribute to disease persistence and which help define anatomical location. Therefore fibroblasts make an attractive therapeutic target as they help orchestrate the inflammatory infiltrate. Current anti-inflammatory therapies target immune cells in an attempt to inhibit the production of pro-inflammatory mediators. However an equally important target is the active induction of pro-resolution programmes responsible for the resolution of inflammation. Fibroblasts are likely to be an important source of these anti-inflammatory mediators. Therapeutic manipulation of fibroblasts and their biologically active products is an emerging concept in treating cancer and is likely to provide a novel method to achieve improved control of chronic inflammatory disease.