Arachidonic acid metabolites and enzyme transcripts in asthma are altered by cigarette smoking.

BACKGROUND: Arachidonic acid metabolites are implicated in the pathogenesis of asthma although only limited information is available on the impact of current smoking history on these metabolites. The aim of the study was to examine the effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations and relevant enzyme transcripts in asthma. METHODS: In 108 smokers and never smokers with asthma and 45 healthy controls [smokers and never smokers], we measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4 , induced sputum fluid LTB4 , LTE4 , PGD2 , and PGE2 , plasma secretory phospholipase A2 (sPLA2 ), and 11ß prostaglandin F2α (11ßPGF2α ), and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA expression levels of arachidonic acid metabolic enzymes. RESULTS: Smokers with asthma had higher urinary LTE4 ; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012 concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157) vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4 (P = 0.013), and plasma 11ßPGF2α (P = 0.032), concentrations, respectively, were increased in smokers with asthma compared with healthy smokers. Asthma-specific and smoking-related increases (>1.5-fold expression) in arachidonate 15-lipoxygenase and gamma-glutamyltransferase transcripts were demonstrated. CONCLUSIONS: Several arachidonic acid metabolites and enzyme transcripts involving both lipoxygenase and cyclooxygenase pathways are increased in smokers with asthma and differ from never smokers with asthma. Possibly targeting specific lipoxygenase and cyclooxygenase pathways that are activated by asthma and cigarette smoking may optimize therapeutic responses.

The role of mast cells and their mediators in reproduction, pregnancy and labour.

BACKGROUND: Mast cells (MCs) are the classical mediators of allergy, however, their importance in the development of innate and adaptive immune responses is increasingly being recognized. Herein, the present MC literature is summarized, with particular focus on studies of MCs in the endometrium and myometrium, and their involvement in fertility, implantation, pregnancy and labour. METHODS: Recent developments in MC biology were identified by systematic searches of PubMed, Medline and Google Scholar from 2000 to November 2009. To specifically examine the role of MCs in fertility and pregnancy, we then performed a systematic review of English literature cited in the PubMed, Medline and Google Scholar databases, but extended the search period, from 1980 to January 2010 RESULTS: MCs can respond to immunoglobulin E-independent innate immune stimuli and are present within the endometrium, with activation and release of mediators occurring prior to menstruation and in association with endometriosis. With respect to pregnancy, MCs are redundant during blastocyst implantation and although their mediators can induce myometrial contractility, there is no epidemiological link of preterm birth with allergy, suggesting a non-essential role or robust regulation. In males, MCs are present in the testes and are increased in oligo- and azoospermia, with MC mediators directly suppressing sperm motility in a potentially reversible manner. CONCLUSIONS: MCs are prevalent in the female and male reproductive tract. However, whether MCs are absolutely required for a successful pregnancy or are fundamental to reproductive pathology, and thereby a therapeutic target, remains to be determined.

Standing magnetic resonance imaging detection of bone marrow oedema-type signal pattern associated with subcarpal pain in 8 racehorses: a prospective study.

REASON FOR PERFORMING STUDY: The proximal metacarpal region is a common site of origin of lameness in the performance horse. A number of disease entities are recognised as causes of proximal metacarpal lameness but a definitive diagnosis is often elusive. Magnetic resonance imaging (MRI) is hypothesised to offer advantages over traditional imaging modalities in the investigation of proximal metacarpal pain. OBJECTIVE: To describe clinical and imaging features of cases of lameness in racehorses arising from the proximal metacarpal region in which standing MRI identified 'bone marrow oedema-type' (BMO-type) signal patterns. METHODS: Records for all horses undergoing standing MRI of the proximal metacarpus/distal carpus from September 2006 to December 2008 were reviewed. Cases underwent a standardised protocol for diagnostic analgesia, radiography and ultrasonography of the proximal metacarpus and distal carpus. Cases with proximal metacarpal lameness displaying a characteristic BMO-type signal pattern on MRI were identified and outcomes analysed. RESULTS: Eight cases were identified with characteristic MRI findings of extensive hyperintensity on T2* gradient echo and short tau inversion fast spin echo sequences and corresponding hypointensity on T1 gradient echo images within the palmaroproximal aspect of the third metacarpal bone. Follow-up information was available for all cases; at the time of writing 7/8 had returned to full work and were free from lameness. CONCLUSIONS: The BMO-type signal patterns visible on MR images in these cases may signal the existence of a previously under-diagnosed pathological process associated with proximal metacarpal lameness in racehorses. This finding is postulated to be associated with a stress reaction and possible prodromal stress fracture of the palmaroproximal metacarpus not appreciable radiographically or ultrasonographically. POTENTIAL RELEVANCE: MRI of the proximal metacarpal region permits detection of pathological processes, which may elude conventional imaging and, therefore, has important therapeutic and prognostic implications in these cases.

Lung abscesses mimicking multiple pulmonary metastases.

Five patients receiving chemotherapy for cancer through Hickman central venous catheters had lung lesions detected by plain chest radiography or computed tomography. In each case these were initially misdiagnosed as metastases, although they ultimately proved to be staphylococcal abscesses. Because of the grave implications of an erroneous diagnosis of metastatic malignant disease, clinicians are urged to consider abscesses in the differential diagnosis of radiological chest abnormalities in such patients.