Melatonin promoted chemotaxins expression in lung epithelial cell stimulated with TNF-α

BACKGROUND: Patients with asthma demonstrate circadian variations in the airway inflammation and lung function. Pinealectomy reduces the total inflammatory cell number in the asthmatic rat lung. We hypothesize that melatonin, a circadian rhythm regulator, may modulate the circadian inflammatory variations in asthma by stimulating the chemotaxins expression in the lung epithelial cell. METHODS: Lung epithelial cells (A549) were stimulated with melatonin in the presence or absence of TNF-α(100 ng/ml). RANTES (Regulated on Activation Normal T-cells Expressed and Secreted) and eotaxin expression were measured using ELISA and real-time RT-PCR, eosinophil chemotactic activity (ECA) released by A549 was measured by eosinophil chemotaxis assay. RESULTS: TNF-α increased the expression of RANTES (307.84 ± 33.56 versus 207.64 ± 31.27 pg/ml of control, p = 0.025) and eotaxin (108.97 ± 10.87 versus 54.00 ± 5.29 pg/ml of control, p = 0.041). Melatonin(10(-10 )to 10(-6)M) alone didn't change the expression of RNATES (204.97 ± 32.56 pg/ml) and eotaxin (55.28 ± 6.71 pg/ml). However, In the presence of TNF-α (100 ng/ml), melatonin promoted RANTES (410.88 ± 52.03, 483.60 ± 55.37, 559.92 ± 75.70, 688.42 ± 95.32, 766.39 ± 101.53 pg/ml, treated with 10(-10), 10(-9), 10(-8), 10(-7),10(-6)M melatonin, respectively) and eotaxin (151.95 ± 13.88, 238.79 ± 16.81, 361.62 ± 36.91, 393.66 ± 44.89, 494.34 ± 100.95 pg/ml, treated with 10(-10), 10(-9), 10(-8), 10(-7), 10(-6)M melatonin, respectively) expression in a dose dependent manner in A549 cells (compared with TNF-α alone, P < 0.05). The increased release of RANTES and eotaxin in A549 cells by above treatment were further confirmed by both real-time RT-PCR and the ECA assay. CONCLUSION: Taken together, our results suggested that melatonin might synergize with pro-inflammatory cytokines to modulate the asthma airway inflammation through promoting the expression of chemotaxins in lung epithelial cell

Mast cells and eosinophils in invasive breast carcinoma

<p>Abstract</p> <p>Background</p> <p>Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas.</p> <p>Methods</p> <p>Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome.</p> <p>Results</p> <p>Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours.</p> <p>Conclusion</p> <p>A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers.</p

An Unusual Case of A Blue Finger

Introduction:Acute discoloration and paresthesia of a distal extremity is concerning for an ischemic event or a manifestation of underlying systemic disease. Achenbach syndrome is an infrequent, but benign etiology of an acute blue finger that needs to be recognized clinically. We present a case to increase awareness. Case:A 57-year-old Caucasian female presented to rheumatology clinic for bruising digits.” She described four episodes of spontaneous segmental, blue discoloration of varying digits over the past two years. Each episode was isolated to a single digit and preceded by 10-15 minutes of throbbing with the digit then turning white and numb. These prodromes were followed by a feeling of “blood vessel popping” with subsequent bruising and mild swelling. Resolution of discoloration ranged from several hours to several days. There was no association with exposure to cold temperatures and warming the fingers would not alleviate the symptoms, nor abort the course. Past medical history includes Raynaud’s disease diagnosed in her twenties. Her current symptoms feel distinctly different from usual Raynaud’s episodes. She is a non-smoker and takes no medications. Family history is non-contributory. Physical exam was unremarkable at presentation and follow up. Photos from the recent episode were available, revealing blue discoloration involving the volar surface of the right 3rd digit at the PIP extending 1cm on either side of the joint with mild swelling, sparing of the distal phalange and no abnormalities of the surrounding digits. Work-up for Raynaud’s included anti-nuclear antibodies and its sub-serologies, anti-phospholipid serologies, complements, complete blood count and complete metabolic panel. These studies were unremarkable and no autoimmune process was identified. The patient also underwent MRA of the right upper extremity, which was non-revealing. Based on the clinical presentation, a diagnosis of Achenbach syndrome was made and the patient was reassured. Discussion:Achenbach syndrome is a benign, self-limiting cause of spontaneous blue finger discoloration that is commonly misdiagnosed as vascular problems, including Raynaud’s. Unlike Achenbach syndrome, Raynaud’s episodes may involve multiple fingers simultaneously, is temperature related and warrants further work-up. In contrast, case studies and case series of Achenbach syndrome suggest futility of angiography and extensive rheumatologic work-up and have not demonstrated any significant disease associations over time. Despite the concerns raised by acuity and appearance, knowledge of Achenbach syndrome along with careful history taking will direct the physician to the correct diagnosis and avoid unnecessary, costly testing