There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

/pdf/european-position-paper-on-rhinosinusitis-and-nasal-polyps-mj734vsl7p.pdf

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The proteoglycan superfamily now contains more than 30 full-time molecules that fulfill a variety of biological functions. Proteoglycans act as tissue organizers, influence cell growth and the maturation of specialized tissues, play a role as biological filters and modulate growth-factor activities, regulate collagen fibrillogenesis and skin tensile strength, affect tumor cell growth and invasion, and influence corneal transparency and neurite outgrowth. Additional roles, derived from studies of mutant animals, indicate that certain proteoglycans are essential to life whereas others might be redundant. The review focuses on the most recent genetic and molecular biological studies of the matrix proteoglycans, broadly defined as proteoglycans secreted into the pericellular matrix. Special emphasis is placed on the molecular organization of the protein core, the utilization of protein modules, the gene structure and transcriptional control, and the functional roles of the various proteoglycans. When possible, proteoglycans have been grouped into distinct gene families and subfamilies offering a simplified nomenclature based on their protein core design. The structure-function relationship of some paradigmatic proteoglycans is discussed in depth and novel aspects of their biology are examined.

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Matrix Proteoglycans: From Molecular Design to Cellular Function

Increasing evidence indicates that chronic obstructive pulmonary disease (COPD) is a complex disease involving more than airflow obstruction. Airflow obstruction has profound effects on cardiac function and gas exchange with systemic consequences. In addition, as COPD results from inflammation and/or alterations in repair mechanisms, the "spill-over" of inflammatory mediators into the circulation may result in important systemic manifestations of the disease, such as skeletal muscle wasting and cachexia. Systemic inflammation may also initiate or worsen comorbid diseases, such as ischaemic heart disease, heart failure, osteoporosis, normocytic anaemia, lung cancer, depression and diabetes. Comorbid diseases potentiate the morbidity of COPD, leading to increased hospitalisations, mortality and healthcare costs. Comorbidities complicate the management of COPD and need to be evaluated carefully. Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. Treatment of COPD inflammation may concomitantly treat systemic inflammation and associated comorbidities. However, new broad-spectrum anti-inflammatory treatments, such as phosphodiesterase 4 inhibitors, have significant side-effects so it may be necessary to develop inhaled drugs in the future. Another approach is the reversal of corticosteroid resistance, for example with effective antioxidants. More research is needed on COPD comorbidities and their treatment.

https://erj.ersjournals.com/content/erj/33/5/1165.full.pdf

Systemic manifestations and comorbidities of COPD

The progressive growth of most neoplasms is dependent upon the establishment of new blood vessels, a process regulated by tumor-secreted factors and matrix proteins. We examined the in vitro and in vivo angiogenic ability of conditioned media obtained from fibrosarcoma, carcinoma, and osteosarcoma cells and their decorin-transfected counterparts. Human endothelial cells were investigated in vitro by evaluating three essential steps of angiogenesis: migration, attachment, and differentiation. On the whole, wild-type tumor cell-secretions enhanced endothelial cell attachment, migration, and differentiation, whereas their decorin-expressing forms inhibited these processes. Similarly, decorin-containing media suppressed endothelial cell sprouting in an ex vivo aortic ring assay. Since angiogenesis is an important component of tumor expansion, the growth rate of these cells as tumor xenografts was examined by implantation in nude mice. In vivo, the decorin-expressing tumor xenografts grew at markedly lower rates and showed a significant suppression of neovascularization. Immunohistochemical, Northern and Western blot analyses indicated that the decorin-expressing cells produced vascular endothelial growth factor (VEGF) at markedly reduced rates vis-a-vis their wild-type counterparts. Specificity of this process was confirmed by experiments where addition of recombinant decorin to the wild-type tumor cells caused 80-95% suppression of VEGF mRNA and protein. These results provide a novel mechanism of action for decorin, and indicate that decorin could adversely affect in vivo tumor growth by suppressing the endogenous tumor cell production of a powerful angiogenic stimulus.

Decorin suppresses tumor cell-mediated angiogenesis.

Oxidative stress in acute ischemic stroke

The levels of two proinflammatory cytokines, namely tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), were investigated in seminal plasma (SP) of proven fertile (n=24) and infertile (n=55) men to evaluate the relationship between diagnosis and semen parameters in a prospective study. Infertile men were divided into four groups as follows: (1) varicocele (n=23), (2) 3 months after varicocelectomy (post-varicocele, n=14), (3) male accessory gland infection (MAGI, n=10) and (4) bilateral testicular atrophy (n=8). IL-6 and TNF-α levels were similar in the SP of fertile and infertile men. There was a strong correlation between the levels of TNF-α and IL-6 in all groups (P 0.05). TNF-α levels were negatively correlated with the sperm motility and morphology (P 0.05). The mean levels of IL-6 in the SP of the MAGI group was higher than in the other groups but did not reach statistical significance. No variation was found in the SP levels of the proinflammatory cytokines studied between the varicocele and the post-varicocele groups. Our results suggest that IL-6 and TNF-α are involved in male fertility. However, their measurement in SP seem to be unsuitable for routine infertility work, perhaps with the exception of men with inflammatory genital diseases.

Relationship between seminal plasma interleukin-6 and tumor necrosis factor α levels with semen parameters in fertile and infertile men

Perlecan is a major heparan sulfate proteoglycan of basement membranes and cell surfaces. Because of its strategic location and ability to store and protect growth factors, perlecan has been implicated in the control of tumor cell growth and metastatic behavior. To test the role of perlecan in malignancy, we generated several stably transfected clones of HT-1080, a human fibrosarcoma cell line, harboring a perlecan cDNA in the antisense orientation. Surprisingly, clones with a reduced synthesis of perlecan mRNA and protein core grew faster, formed larger colonies in semisolid agar, and induced faster formation of s.c. tumors in nude mice than the wild-type cells. Their growth properties in vitro were independent of exogenous basic fibroblast growth factor. Reduction of perlecan expression was associated with three distinct properties typical of tumor cells with a more aggressive phenotype: enhanced migration through 8-µm-pore filter, increased invasion in Matrigel-coated filters, and heightened adhesiveness to type IV collagen substrata. These results thus provide the first evidence that perlecan may inhibit the growth and invasiveness of fibrosarcoma cells in a basic fibroblast growth factor-independent pathway and raise the possibility that perlecan may prevent the infiltration of host tissues in mesenchymal neoplasms.

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A Role for Perlecan in the Suppression of Growth and Invasion in Fibrosarcoma Cells

In COPD, the systemic effects of the disease reflect the structural and/or biochemical alterations occurring in the structures or organs other than the lungs in relation to the characteristics of the primary disease. The disorders of endothelial structures due to COPD may lead vascular pathologies, such as ischemic heart disease, stroke, to occur more commonly in those with COPD. On consideration of the fact that the vascular endothelium is a major site in which the systemic effect of the inflammation occurs, should von Willebrand Factor, a clotting factor of endothelium origin, and the plasma level of fibrinogen vary with the severity of the disease in COPD, the variability of arterial blood gas values, and the stability or exacerbation of the disease? Considering the fact that microalbuminuria is an indirect manifestation of the renal endothelial permeability and/or renal perfusion; should there be an association between microalbuminuria and the severity of COPD? Therefore, in order to assess the effect of the systemic inflammation in COPD on the vascular endothelium, we compared the levels of the plasma vWF, fibrinogen, 24-h urine microalbuminuria of those with stable COPD (33 patients) and exacerbation of COPD (26 patients) with those of the controls (16 healthy subjects). The mean age was 63.42 ∓ 10.29, 68.00 ∓ 9.77 and 59.63 ∓ 14.10 years in SCOPD, COPDAE, and CG, respectively. The level of microalbuminuria was found to increase significantly in COPDAE group, compared to that of the controls (P = 0.004). When we investigated the relation between smoking burden and microalbuminuria, vWF, fibrinogen levels, the amount of consumption and positive relationship were found significant. (r = 0.336, P = 0.003 between smoking pack-years and vWF, r = 0.403, P = 0.001 between smoking pack-years and fibrinogen, and r = 0.262, P = 0.02 between smoking pack-years and microalbuminuria). The levels of vWF and fibrinogen are AECOPD > SCOPD > CG, with the highest being in AECOPD, and the difference among the groups was statistically significant. The relationship between the level of hypoxemia and microalbuminuria, fibrinogen and vWF was found to be significant (r = −0.360, P = 0.005 between oxygen saturation and microalbuminuria, r = −0.359, P = 0.005 between the level of PaO2 and fibrinogen, and r = −0.336, P = 0.009 between PaO2 and vWF). In conclusion, the levels of plasma vWF, fibrinogen, and microalbuminuria may be helpful in grading the severity of COPD exacerbation. The related increase in these markers may represent a possible pathophysiological mechanism behind the increased vascular morbidity of patients with COPD and detecting indirectly the endothelial dysfunction as a manifestation of systemic outcomes due to COPD and in detecting earlier the cases in which the risk for developing the associated complications are higher. We suggest that further studies are necessary to investigate the impact of antithrombotic treatment on microalbuminuria, plasma vWF and fibrinogen as markers of endothelial dysfunction coexisting COPD exacerbation.

Cigdem Yenisey

Papers

Decorin suppresses tumor cell-mediated angiogenesis.

Oxidative stress in acute ischemic stroke

Relationship between seminal plasma interleukin-6 and tumor necrosis factor α levels with semen parameters in fertile and infertile men

A Role for Perlecan in the Suppression of Growth and Invasion in Fibrosarcoma Cells

Microalbuminuria, von Willebrand factor and fibrinogen levels as markers of the severity in COPD exacerbation.