Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.     

Effect of a thrombin receptor (protease-activated receptor 1, PAR-1) gene polymorphism in chronic hepatitis C liver fibrosis

Background and Aim:  Tissue injury leads to activation of coagulation and generation of thrombin. Inhibition of thrombin receptor protease-activated receptor 1 (PAR-1) has been shown to reduce liver fibrosis in animals. This study aimed to evaluate the effect of PAR-1 gene polymorphism on rate of liver fibrosis (RF) in chronic hepatitis C.
Methods:  Polymorphisms studied: C > T transition 1426 bp upstream of translation start site (-1426C/T), 13 bp repeat of preceding -506 5'-CGGCCGCGGGAAG-3' sequence (-506I/D), and A > T transversion in intervening sequence (IVS) 14 bp upstream of exon-2 start site (IVS-14A/T). A total of 287 European and 90 Brazilian patients were studied.
Results:  1426C/T polymorphism: There was a trend to higher RF in patients with the TT genotype ( P  = 0.06) and an association between genotype CC and slow fibrosis ( P  = 0.03) in Europeans. In males, RF was significantly higher in those with the TT genotype compared to CT ( P  = 0.003) and CC ( P  = 0.007). There was a significant association between TT and fast fibrosis ( P  = 0.04). This was confirmed in an independent cohort of Brazilians where RF was higher in TT than in CC ( P  = 0.03). Analysis of -506I/D showed no difference in RF and distribution of slow/fast fibrosis among different genotypes in both populations. Analysis of IVS-14A/T showed no difference between genotypes.
Conclusion:  In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis.     

Alterations of Granulopoiesis Following Chemotherapy

Clonal proliferation of marrow granulocytic progenitor cells (GPC) in vitro andthe daily urinary output of granulocyticcolony-stimulating factor (CSF) were determined in two patients with acutemyeloid leukemia (AML) in remission andone patient with malignant lymphoma receiving monthly pulses of chemotherapywith cytosine arabinoside and 6-thioguanine. During and immediately following therapy, a marked decrease of granulocytic colony-forming capacity (CFC)occurred, with an increase and return tobasal levels by 3-4 wk. In the AMLpatients, the proportion of GPC in DNAsynthesis (GPC-S), as determined by thethymidine suicide technique, declinedfrom basal levels (31%-39%) to 0%-26% after 2 days of treatment. This wasfollowed by a sharp rise in GPC-S to41%-75% 1-3 days posttherapy, with anoscillatory return of GPC-S to basal levelsby 3-4 wk. In all courses a marked increase of urinary CSF output occurredduring or 1 day posttherapy, concomitantwith the rise of the proportion of GPC-S.In the lymphoma patient, an initially highproportion of marrow GPC-S and low CFCanticipated the severe neutropenia whichfollowed therapy. These results provide abasis for determining the efficacy withwhich cytotoxic drugs destroy proliferativeactivity of GPC and for assessing thepotential for hemopoietic toxicity following chemotherapy.

Submitted on August 10, 1973 Accepted on February 27, 1974     

Ultrafast transient absorption of eumelanin suspensions: the role of inverse Raman scattering

An ultrafast investigation is carried out on synthetic eumelanin suspended either in water or in DMSO-methanol. Upon photoexcitation by visible femtosecond pulses, the transient absorption (TA) dynamics of the suspensions are probed in a broad visible spectral range, showing clear nonlinearities. The latter arise from pump-probe interactions that induce the inverse Raman scattering (IRS) effect. We show how eumelanin TA dynamics are modified in proximity of the solvent Stokes and anti-Stokes scattering peaks, demonstrating that IRS affects the sign of TA but not the relaxation times. We compare the results obtained in both suspensions, unveiling the role of the surrounding environment. Eventually, the intrinsic response of synthetic eumelanin to ultrafast photoexcitation is evaluated.OCIS codes: (160.1435) Biomaterials, (320.7150) Ultrafast spectroscopy, (300.6240) Spectroscopy, coherent transient, (190.5890) Scattering, stimulated     

Bacterial isolates from infected wounds and their antibiotic susceptibility pattern: some remarks about wound infection

Wound infection plays an important role in the development of chronicity, delaying wound healing. This study aimed to identify the bacterial pathogens present in infected wounds and characterise their resistance profile to the most common antibiotics used in therapy. Three hundred and twelve wound swab samples were collected from 213 patients and analysed for the identification of microorganisms and for the determination of their antibiotic susceptibility. Patients with diverse type of wounds were included in this retrospective study, carried out from March to September 2012. A total of 28 species were isolated from 217 infected wounds. The most common bacterial species detected was Staphylococcus aureus (37%), followed by Pseudomonas aeruginosa (17%), Proteus mirabilis (10%), Escherichia coli (6%) and Corynebacterium spp. (5%). Polymicrobial infection was found in 59 (27·1%) of the samples and was mainly constituted with two species. The most common association was S. aureus/P. aeruginosa. All Gram‐positives were susceptible to vancomycin and linezolid. Gram‐negatives showed quite high resistance to the majority of antibiotics, being amikacin the most active against these bacteria. This study is mostly oriented to health care practitioners who deal with wound management, making them aware about the importance of wound infection and helping them to choose the adequate treatment options to control microbial infection in wounds.     

Comprehensive Treatment of Periorbital Region with Hyaluronic Acid

The periorbital subunit is one of the first facial regions to show signs of aging, primarily due to volume depletion of the soft tissue and bony resorption. Surgical and office-based nonsurgical procedures form an important basis for periorbital rejuvenation. It is important to make a detailed clinical evaluation of the patient to indicate the most appropriate procedure to be performed. With the objective of showing a nonsurgical procedure for the rejuvenation of the periorbital area, the authors describe a technique of applying fillers in the upper and lower periorbital regions, paying attention to the anatomy of this facial region and the type of product to be used besides the expected results of the procedure and its possible adverse effects and complications. The nonsurgical rejuvenation of the periorbicular region with hyaluronic acid is a new and innovative technique. In the opinion of the authors, it is a great aesthetic impact area and consequently brings high satisfaction to patients.Maintaining a youthful and pleasant appearance of the face in today’s culture impacts quality of life in many patients. The facial contour remodeling is being revolutionized by new nonsurgical techniques.Facial aging is a complex and dynamic process. All people age differently as a result of imbalance, disharmony, and disproportion of the aging process between the overlying soft tissue and the underlying bony frameworks.1 The upper periorbital subunit is one of the first facial regions to show signs of aging, and even minor changes in its structure and volume can distort the perceived emotions and health of patients.2 An aesthetic and youthful upper periorbital subunit is characterized by a well-defined brow of appropriate height and shape, fullness of the upper periorbit, a crisp and well-defined upper eyelid crease, minimal skin excess, and good skin quality.3,4In the aging process of this facial area, one group of patients displays signs of aging due predominantly to soft tissue ptosis of the upper eyelid, requiring surgical excision. Another group presents with volume depletion of the soft tissue and bony resorption of the orbit. The loss of septal support, leading to brow prolapse and an exacerbation of upper eyelid fullness and congestion, can also contribute to the aging process. This appearance is characterized by deflation of the upper eyelid as well as hollowing and visibility of the supraorbital bony rim, leading to a sunken, hollow, and skeletonized orbit, which can make the patient appear sickly, anorexic, and old. In recent years, modern facial rejuvenation surgery has evolved toward volume restoration in addition to tissue suspension.2Comprehensive analysis of both soft tissue and bony structural changes are essential for the periorbital rejuvenation. Surgical procedures and office-based nonsurgical procedures form an important basis for periorbital rejuvenation, including cosmeceuticals, chemical peels, laser and light treatments, neurotoxins, and fillers. Improved understanding of the pathophysiology of aging and technical advancements in nonsurgical techniques has enabled us to achieve better and more comprehensive improvement for patients.5