[House dust mite allergy]

House dust mites can be found all over the world where human beings live independent from the climate. Proteins from the gastrointestinal tract- almost all known as enzymes - are the allergens which induce chronic allergic diseases. The inhalation of small amounts of allergens on a regular base all night leads to a slow beginning of the disease with chronically stuffed nose and an exercise induced asthma which later on persists. House dust mites grow well in a humid climate - this can be in well isolated dwellings or in the tropical climate - and nourish from human skin dander. Scales are found in mattresses, upholstered furniture and carpets. The clinical picture with slowly aggravating complaints leads quite often to a delayed diagnosis, which is accidently done on the occasion of a wider spectrum of allergy skin testing. The beginning of a medical therapy with topical steroids as nasal spray or inhalation leads to a fast relief of the complaints. Although discussed in extensive controversies in the literature - at least in Switzerland with the cold winter and dry climate - the recommendation of house dust mite avoidance measures is given to patients with good clinical results. The frequent ventilation of the dwelling with cold air in winter time cause a lower indoor humidity. Covering encasings on mattresses, pillow, and duvets reduces the possibility of chronic contact with mite allergens as well as the weekly changing the bed linen. Another option of therapy is the specific immunotherapy with extracts of house dust mites showing good results in children and adults. Using recombinant allergens will show a better quality in diagnostic as well as in therapeutic specific immunotherapy.

Fas-activated serine/threonine phosphoprotein promotes immune-mediated pulmonary inflammation

We generated Fas-activated serine threonine phosphoprotein (FAST)-deficient mice (FAST(-/-)) to study the in vivo role of FAST in immune system function. In a model of house dust mite-induced allergic pulmonary inflammation, wild type mice develop a mixed cellular infiltrate composed of eosinophils, lymphocytes, and neutrophils. FAST(-/-) mice develop airway inflammation that is distinguished by the near absence of neutrophils. Similarly, LPS-induced alveolar neutrophil recruitment is markedly reduced in FAST(-/-) mice compared with wild type controls. This is accompanied by reduced concentrations of cytokines (TNF-alpha and IL-6 and -23) and chemoattractants (MIP-2 and keratinocyte chemoattractant) in bronchoalveolar lavage fluids. Because FAST(-/-) neutrophils exhibit normal chemotaxis and survival, impaired neutrophil recruitment is likely to be due to reduced production of chemoattractants within the pulmonary parenchyma. Studies using bone marrow chimeras implicate lung resident hematopoietic cells (e.g., pulmonary dendritic cells and/or alveolar macrophages) in this process. In conclusion, our results introduce FAST as a proinflammatory factor that modulates the function of lung resident hematopoietic cells to promote neutrophil recruitment and pulmonary inflammation.

[Allergies to animals and fungi]

Allergies to animals are behind the house-dust mite allergy the most frequent cause for indoor allergic respiratory symptoms. In case of persistent allergen exposure symptoms like rhinitis, itch of the skin or asthma are usually not perceived intensively and, thus, can not assigned to an animal or an animal source. In many cases animal allergies are based on a perennial allergen exposure. Although most likely all animals may be the cause of a respiratory allergy, cats, dogs, and horses are the most frequent elicitors. The diagnosis of an allergy to an animal needs to be set with due care, since it often causes emotional reactions, diverse conflicts, but also lack of understanding. Rarer are allergies to fungi even though fungi as allergen sources since decades belong to the differential diagnosis in respiratory allergies particularly in case of late summer asthma. Fungi are ubiquitous and present indoors as well as outdoors. Unfortunately the field of fungal allergy is not well explored and diagnostic possibilities are limited. The most promising therapy in both allergy to animals and fungi would be complete avoiding of contact with the respective allergen source. Indeed many preventive recommendations are given; however, realization is often not successful. In selected cases specific immunotherapy for both animal and fungal allergies is a potential therapeutic option.

Eczematous skin reaction to atopy patch testing with cockroach in patients with atopic dermatitis

BACKGROUND: Aeroallergens from house dust mite (HDM) may be an important trigger in a subgroup of patients with atopic dermatitis (AD). HDM and cockroach (CR) contain cross-reactive allergens, such as tropomyosin. OBJECTIVE: To investigate the diagnostic value of patch testing with an aeroallergen and the role of CR allergen and HDM allergen in persons with AD. METHODS: We performed skin prick tests (SPT) with a panel of common aeroallergens and total serum immunoglobulin (Ig)E and specific IgE tests for CR and HDM on 23 patients with AD and 9 nonatopic control participants. Atopy patch tests (APT) were performed with CR and HDM extracts on clinically uninvolved skin on the back, and evaluated after 48 and 72 hours. RESULTS: A positive APT reaction to CR was found in 10/23 (43%) patients with AD. No positive reactions were observed in the nonatopic control participants. Positive APT reactions for CR showed no significant correlation with SPT or specific IgE levels for this allergen. Twelve of the 23 (52%) patients with AD were also sensitized to HDM. There was no significant correlation between positive results for SPT, APT, and specific IgE to CR and HDM. CONCLUSION: We demonstrate that CR allergens can induce positive patch test reactions in patients with AD. The absence of a significant correlation to SPT and specific IgE antibodies suggests that T-cell- and IgE-sensitization may be mediated by different allergens. There was no significant relationship between CR and HDM sensitivity, thus indicating no major cross-reactivity.

Expression of thymic stromal lymphopoietin in canine atopic dermatitis

BACKGROUND In humans, thymic stromal lymphopoietin (TSLP) plays a central role in the development of allergic inflammation, such as atopic dermatitis (AD), but it is unknown whether it is involved in the pathogenesis of canine AD (CAD). HYPOTHESIS/OBJECTIVES Our aim was to characterize canine TSLP and to assess its expression in CAD. METHODS Canine TSLP was identified based on sequence homology with human TSLP and the complementary DNA (cDNA) cloned by RT-PCR. Real-time quantitative RT-PCR was established to assess the expression of canine TSLP in cultured canine keratinocytes and in skin biopsy specimens from lesional and nonlesional skin of 12 dogs with CAD and eight healthy control dogs. RESULTS Partial canine TSLP cDNA was cloned and characterized. It contained four exons that shared 70 and 73% nucleotide identity with human and equine TSLP, respectively, encoding the signal peptide and full-length secreted protein. We found significantly increased TSLP expression in lesional and nonlesional skin of dogs with CAD compared with healthy control dogs (P < 0.05), whereas no difference was measured between lesional and nonlesional samples. In cultured primary canine keratinocytes, we found increased TSLP expression after stimulation with house dust mite allergen extract or Toll-like receptor ligands lipopolysaccharide and poly I:C. CONCLUSIONS AND CLINICAL IMPORTANCE Increased TSLP expression in the skin of dogs with CAD supports an involvement of TSLP in the pathogenesis of CAD similar to that in humans. Further studies should elucidate the function and therapeutic potential of TSLP in CAD.

Effects of ex vivo γ-tocopherol on airway macrophage function in healthy and mild allergic asthmatics

Elevated inflammation and altered immune responses are features found in atopic asthmatic airways. Recent studies indicate γ-tocopherol (GT) supplementation can suppress airway inflammation in allergic asthma. We studied the effects of in vitro GT supplementation on receptor-mediated phagocytosis and expression of cell surface molecules associated with innate and adaptive immunity on sputum-derived macrophages. Cells from nonsmoking healthy (n = 6) and mild house dust mite-sensitive allergic asthmatics (n = 6) were treated ex vivo with GT (300 µM) or saline (control). Phagocytosis of opsonized zymosan A bioparticles (Saccharomyces cerevisiae) and expression of surface molecules associated with innate and adaptive immunity were assessed using flow cytometry. GT caused significantly decreased (p < 0.05) internalization of attached zymosan bioparticles and decreased (p < 0.05) macrophage expression of CD206, CD36 and CD86 in allergic asthmatics but not in controls. Overall, GT caused downregulation of both innate and adaptive immune response elements, and atopic status appears to be an important factor.

Effects of lung recruitment maneuvers on splanchnic organ perfusion during endotoxin-induced pulmonary arterial hypertension

Lung recruitment maneuvers (RMs), used to reopen atelectatic lung units and to improve oxygenation during mechanical ventilation, may result in hemodynamic impairment. We hypothesize that pulmonary arterial hypertension aggravates the consequences of RMs in the splanchnic circulation. Twelve anesthetized pigs underwent laparotomy and prolonged postoperative ventilation. Systemic, regional, and organ blood flows were monitored. After 6 h (= baseline), a recruitment maneuver was performed with sustained inflation of the lungs. Thereafter, the pigs were randomly assigned to group C (control, n = 6) or group E with endotoxin-induced pulmonary arterial hypertension (n = 6). Endotoxemia resulted in a normotensive and hyperdynamic state and a deterioration of the oxygenation index by 33%. The RM was then repeated in both groups. Pulmonary artery pressure increased during lipopolysaccharide infusion from 17 ± 2 mmHg (mean ± SD) to 31 ± 10 mmHg and remained unchanged in controls (P < 0.05). During endotoxemia, RM decreased aortic pulse pressure from 37 ± 14 mmHg to 27 ± 13 mmHg (mean ± SD, P = 0.024). The blood flows of the renal artery, hepatic artery, celiac trunk, superior mesenteric artery, and portal vein decreased to 71% ± 21%, 69% ± 20%, 76% ± 16%, 79% ± 18%, and 81% ± 12%, respectively, of baseline flows before RM (P < 0.05 all). Organ perfusion of kidney cortex, kidney medulla, liver, and jejunal mucosa in group E decreased to 65% ± 19%, 77% ± 13%, 66% ± 26%, and 71% ± 12%, respectively, of baseline flows (P < 0.05 all). The corresponding recovery to at least 90% of baseline regional blood flow and organ perfusion lasted 1 to 5 min. Importantly, the decreases in regional blood flows and organ perfusion and the time to recovery of these flows did not differ from the controls. In conclusion, lipopolysaccharide-induced pulmonary arterial hypertension does not aggravate the RM-induced significant but short-lasting decreases in systemic, regional, and organ blood flows.

SphK1 regulates proinflammatory responses associated with endotoxin and polymicrobial sepsis

During sepsis, activation of phagocytes leads to the overproduction of proinflammatory cytokines, causing systemic inflammation. Despite substantial information regarding the underlying molecular mechanisms that lead to sepsis, several elements in the pathway remain to be elucidated. We found that the enzyme sphingosine kinase 1 (SphK1) is up-regulated in stimulated human phagocytes and in peritoneal phagocytes of patients with severe sepsis. Blockade of SphK1 inhibited phagocyte production of endotoxin-induced proinflammatory cytokines. We observed protection against sepsis in mice treated with a specific SphK1 inhibitor that was enhanced by treatment with a broad-spectrum antibiotic. These results demonstrated a critical role for SphK1 in endotoxin signaling and sepsis-induced inflammatory responses and suggest that inhibition of SphK1 is a potential therapy for septic shock.

Diabetes-related knowledge among medical and nursing house staff

To assess the diabetes-related knowledge of medical and nursing house staff with particular focus on inpatient diabetes management and insulin therapy.

Sperm morphology, swimming velocity, and longevity in the house sparrow Passer domesticus

Sperm competition exerts strong selection on males to produce spermatozoa with an optimal morphology that maximizes their fertilization success. Long sperm were first suggested to be favored because they should swim faster. However, studies that investigated the relationship between sperm length and sperm competitive ability or sperm swimming velocity yielded contradictory results. More recently, ratios of the different sections of a spermatozoon (the head, midpiece, and flagellum) were suggested to be more crucial in determining swimming velocity. Additionally, sperm ability to remain and survive in the female storage organs may also influence fertilization success, so that optimal sperm morphology may rather maximize sperm longevity than velocity. In this study, we investigated how sperm morphology is related to sperm velocity and sperm longevity in the house sparrow Passer domesticus. Sperm velocity was found to be correlated with head/flagellum ratio. Sperm with small heads relative to their flagellum showed higher swimming velocity. Additionally, shorter sperm were found to live longer. Finally, we found sperm morphological traits to vary substantially within males and the head/flagellum ratio to be unrelated to total sperm length. We discuss the hypothesis that the substantial within-male variation in sperm morphology reflects a male strategy to produce a diversity of sperm from long, fast-swimming to short, long-living sperm to maximize their fertilization success in a context of sperm competition.