The Influence of 5-Fluorouracil on the Endothelium in Small Arteries. An Electron Microscopic Study in Rabbits

5-Fluorouracil (5-FU) is a widely used antineoplastic agent. 5-FU induced cardiotoxicity is a still relatively unknown side-effect of this drug. This phenomenon could be due to a direct cytotoxic effect on the endothelial cells. We tested this hypothesis in an experimental study in rabbits, by scanning or transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear) after in vivo treatment with 5-FU. Both local and systemic effects of 5-FU on endothelium were studied 15, 30, 60 and 120 minutes after intra-arterial or intraperitoneal treatment. Perfusion fixation at physiological pressure and temperature was used in order to minimize damage to the endothelium during the preparation procedure. Eighteen rabbits weighing 2.5-3.0 kg were used, and 6 animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell edema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter a scale of negative points was used. Irreversible cell damage was observed in 5-FU treated animals: disruption of the endothelial sheet and patchy exposure of the subendothelium, sometimes as a focus for thrombus formation. Our findings support the hypothesis that the thrombogenic effect of 5-FU secondary to its direct cytotoxic effect on endothelium might be one of the pathophysiological mechanisms behind 5-FU induced cardiotoxicity

The Appearance of Endothelium in Small Arteries After Treatment with 5-Fluorouracil. An Electron Microscopic Study of Late Effects in Rabbits

Cardiotoxicity is an unexplained toxic manifestation of 5-fluorouracil (5-FU). Its possible mechanism could be a direct cytotoxic effect on the vascular endothelium. We have tested this hypothesis in an experimental study in rabbits, using scanning and transmission electron microscopic evaluation of endothelium in small arteries (the central artery of the ear). The perfusion fixation method at physiological pressure and temperature was used. Both local and systemic effects of 5-FU on endothelium were studied 1, 3, 7, 14 and 30 days after in vivo treatment with 5-FU. Fifteen rabbits were used and five additional animals served as controls. The following parameters were evaluated: vessel wall and endothelial cell contraction, cell oedema, cytolysis, occurrence of denuded areas, platelet adhesion/aggregation and fibrin formation. For the description of each parameter, a scale of negative points (0.0-3.0) was used. We found severe cell damage with accompanying thrombus formation. The findings support the hypothesis that the thrombogenic effect of 5-FU, secondary to its direct cytotoxic effect on endothelium, is the pathophysiological mechanism behind 5-FU cardiotoxicity

Acute Effects of a Fungal Volatile Compound

Objective: 3-Methylfuran (3-MF) is a common fungal volatile product with active biologic properties, and previous studies have indicated a contribution to airway disease. The aim of the present study was to assess the acute health effects of this compound in humans. Design: Acute effects were assessed via chamber exposure to (1 mg/m(3)) 3-MF. Participants and measurements: Twenty-nine volunteers provided symptom reports, ocular electromyograms, measurement of eye tear film break-up time, vital staining of the eye, nasal lavage, acoustic rhinometry, transfer tests, and dynamic spirometry. Results: No subjective ratings were significantly increased during exposure. Blinking frequency and the lavage biomarkers myeloperoxidase and lysozyme were significantly increased, and forced vital capacity was significantly decreased during exposure to 3-MF compared with air control. Conclusions and relevance to clinical practice: Acute effects in the eyes, nose, and airways were detected and might be the result of the biologically active properties of 3-MF. Thus, 3-MF may contribute to building-related illness

Can air pollution affect tear film stability? a cross-sectional study in the aftermath of an explosion accident

<p>Abstract</p> <p>Background</p> <p>After an explosion and fire in two tanks containing contaminated oil and sulphur products in a Norwegian industrial harbour in 2007, the surrounding area was polluted. This caused an intense smell, lasting until the waste was removed two years later. The present study reports examinations of tear film break up time among the population. The examinations were carried out because many of the people in the area complained of sore eyes. The purpose of the study was to assess the relationship between living or working close to the polluted area and tear film stability one and a half years after the explosion.</p> <p>Methods</p> <p>All persons working or living in an area less than six kilometres from the explosion site were invited to take part in the study together with a similar number of persons matched for age and gender living more than 20 kilometres away. Three groups were established: workers in the explosion area and inhabitants near the explosion area (but not working there) were considered to have been exposed, and inhabitants far away (who did not work in the explosion area) were considered to be unexposed. A total of 734 people were examined, and the response rate was 76 percent. Tear film stability was studied by assessing non-invasive break-up time (NIBUT) using ocular microscopy. In addition Self-reported Break Up Time (SBUT) was assessed by recording the time the subject could keep his or hers eyes open without blinking when watching a fixed point on a wall. Background information was obtained using a questionnaire. Non-parametric Wilcoxon-Mann-Whitney-tests with exact p-values and multiple logistic regression analyses were performed.</p> <p>Results</p> <p>Both NIBUT and SBUT were shorter among the male exposed workers than among the inhabitants both near and far away from the explosion area. This was also found for SBUT among males in a multiple logistic regression analysis, adjusting for age and smoking.</p> <p>Conclusions</p> <p>Reduced tear film stability was found among workers in an area where an explosion accident had occurred.</p

Infusion fluids contain harmful glucose degradation products

PURPOSE: Glucose degradation products (GDPs) are precursors of advanced glycation end products (AGEs) that cause cellular damage and inflammation. We examined the content of GDPs in commercially available glucose-containing infusion fluids and investigated whether GDPs are found in patients' blood. METHODS: The content of GDPs was examined in infusion fluids by high-performance liquid chromatography (HPLC) analysis. To investigate whether GDPs also are found in patients, we included 11 patients who received glucose fluids (standard group) during and after their surgery and 11 control patients receiving buffered saline (control group). Blood samples were analyzed for GDP content and carboxymethyllysine (CML), as a measure of AGE formation. The influence of heat-sterilized fluids on cell viability and cell function upon infection was investigated. RESULTS: All investigated fluids contained high concentrations of GDPs, such as 3-deoxyglucosone (3-DG). Serum concentration of 3-DG increased rapidly by a factor of eight in patients receiving standard therapy. Serum CML levels increased significantly and showed linear correlation with the amount of infused 3-DG. There was no increase in serum 3-DG or CML concentrations in the control group. The concentration of GDPs in most of the tested fluids damaged neutrophils, reducing their cytokine secretion, and inhibited microbial killing. CONCLUSIONS: These findings indicate that normal standard fluid therapy involves unwanted infusion of GDPs. Reduction of the content of GDPs in commonly used infusion fluids may improve cell function, and possibly also organ function, in intensive-care patients

Can Low-Severity Fire Reverse Compositional Change in Montane Forests of the Sierra Nevada, California, USA?

Throughout the Sierra Nevada, nearly a century of fire suppression has altered the tree species composition, forest structure, and fire regimes that were previously characteristic of montane forests. Species composition is fundamentally important because species differ in their tolerances to fire and environmental stressors, and these differences dictate future forest structure and influence fire regime attributes. In some lower montane stands, shade-tolerant, fire-sensitive species have driven a threefold increase in tree density that may intensify the risk of high-severity fire. In upper montane forests, which were historically characterized by longer fire return intervals, the effects of fire exclusion are both less apparent and less studied. Although land managers have been reintroducing fire to lower and upper montane forests for \u3e4 decades, the potentially restorative effects of these actions on species composition remain largely unassessed. We used tree diameter and species data from 51 recently burned and 46 unburned plots located throughout lower and upper montane forests in Yosemite National Park and Sequoia & Kings Canyon National Parks to examine the effects of low-to moderate-severity (hereafter, lower-severity)fire on the demography of seven prevalent tree species. The density of Abies concolor concolor 30–45 cm dbh, A. magnifica Calocedrus decurrens concolor but not for C. decurrens, and (2) variability in tree density among plots that burned at lower severity exceeded the range of tree densities reported in historical data sets. High proportions of shade-tolerant species in some postfire stands may increase the prevalence of shade-tolerant species in the future, a potential concern for managers who seek to minimize ladder fuels and promote forest structure that is less prone to high-severity fire

Obesity and nocturnal gastro-oesophageal reflux are related to onset of asthma and respiratory symptoms

Several studies have identified obesity as a risk factor for asthma in both children and adults. An increased prevalence of asthma in subjects with gastro-oesophageal reflux (GOR) and obstructive sleep apnoea syndrome has also been reported. The aim of this investigation was to study obesity, nocturnal GOR and snoring as independent risk factors for onset of asthma and respiratory symptoms in a Nordic population. In a 5-10 yr follow-up study of the European Community Respiratory Health Survey in Iceland, Norway, Denmark, Sweden and Estonia, a postal questionnaire was sent to previous respondents. A total of 16,191 participants responded to the questionnaire. Reported onset of asthma, wheeze and night-time symptoms as well as nocturnal GOR and habitual snoring increased in prevalence along with the increase in body mass index (BMI). After adjusting for nocturnal GOR, habitual snoring and other confounders, obesity (BMI >30) remained significantly related to the onset of asthma, wheeze and night-time symptoms. Nocturnal GOR was independently related to the onset of asthma and in addition, both nocturnal GOR and habitual snoring were independently related to onset of wheeze and night-time symptoms. This study adds evidence to an independent relationship between obesity, nocturnal gastro-oesophageal reflux and habitual snoring and the onset of asthma and respiratory symptoms in adults

Upalni i hematotoksični potencijal metabolita plijesni Stachybotrys chartarum (Ehrenb.) Hughes u zatvorenim prostorijama

Mould Stachybotrys chartarum (Ehrenb.) Hughes is known to pose a health risk in indoor environments. Most of its strains can produce several intra- and extracellular trichothecene mycotoxins. Complex secondary metabolites of stachybotrys isolates from mouldy dwellings/public buildings in Slovakia were intratracheally instilled in Wistar male rats (4 μg in 0.2 mL of 0.2 % dimethylsulphoxide; diacetoxyscirpenol as the positive control). After three days, haematological parameters were measured in peripheral blood and infl ammatory response biomarkers in bronchoalveolar lavage fl uid (BALF), and the results were statistically analysed. Exometabolites proved to suppress red blood cell (RBC), decreasing the total RBC count, haemoglobin, and haematocrit. The exposed rats showed signifi cantly higher total BALF cell count, indicating infl ammation, lower alveolar macrophage counts, and increased granulocyte count related to the BALF cells. Due to haematotoxic and infl ammation-inducing properties, metabolites of S. chartarum can cause damage to the airways and haematological disorders in occupants of mouldy buildings.Plijesan Stachybotrys chartarum (Ehrenb.) Hughes poznata je kao rizični mikroorganizam u zatvorenim prostorijama. Većina njezinih sojeva može proizvesti nekoliko unutarstaničnih i izvanstaničnih trikotecenskih mikotoksina. Muškim Wistar štakorima instilirani su intratrahealno kompleksni sekundarni metaboliti stahibotrisa izolirani iz stambenih i javnih zgrada u Slovačkoj zahvaćenima plijesni (4 μg na 0,2 mL 0,2 %-tnog dimetilsulfoksida; dok se diacetoksiscirpenol rabio kao pozitivna kontrola). Tri dana kasnije izmjereni su hematološki parametri u perifernoj krvi te biopokazatelji upalnoga odgovora u bronhoalveolarnome ispirku te su rezultati obrađeni statistički. Pokazalo se da egzometaboliti suprimiraju eritrocite, smanjujući njihov ukupni broj, hemoglobin i hematokrit. Izloženi štakori imali su značajno veći broj stanica u bronhoalveolarnome ispirku, što upućuje na upalu, dok im je broj alveolarnih makrofaga bio manji, a broj granulocita povezanih sa stanicama u ispirku veći. Zbog svojih hematotoksičnih i upalnih svojstava S. chartarum može dovesti do oštećenja dišnih putova i poremećaja u krvotvornome sustavu osoba koje žive i/ili rade u zgradama zahvaćenima tom plijesni