Avian mite dermatitis: Diagnostic challenges and unmet needs.

The avian mite Dermanyssus gallinae (poultry red mite, PRM) is of major economic and veterinary importance for the poultry and egg industry worldwide. The accumulating reports on the opportunistic nonavian feeding of D. gallinae raise concerns on PRM host expansion. However, the consequent threats to human health remain largely unclear. PRM infestation in humans is usually manifested as a local or generalized noncharacteristic skin reaction referred to as gamasoidosis. This report presents the current state of the art and the new developments on PRM-associated dermatitis, sharing neither the authors' personal experience nor focusing on differential diagnosis. Specifically, it reflects the outcome of the critical assessment of the available literature by European medical and veterinary experts in the field under the "One Health" approach.

Comparable profiles of serum histamine and IgG4 levels in allergic beekeepers.

Growing evidence identifies histamine as a key player in allergic responses, but the reports relating serum histamine to tolerance are scarce and inconclusive. This study investigated the relationship of circulating histamine to the tolerant phenotype in allergic beekeepers. The results showed a positive correlation between the serum levels of histamine and specific immunoglobulin G4 (sIgG4) to honeybee venom, but not with total IgE or sIgE. Interestingly, both sIgG4 and histamine levels were negatively correlated with the time since the last bee sting. In contrast to total IgE and sIgE, serum sIgG4 and histamine levels followed comparable patterns, being higher in tolerant/recently stung individuals and lower in the least frequently stung subgroup. The data obtained in this pilot study associated, for the first time, serum histamine levels with allergen tolerance in allergic individuals and provided the lead for further considering the putative immunomodulatory properties of histamine in allergic responses.

Disease activity only moderately correlates with quality of life impairment in patients with chronic spontaneous urticaria.

BACKGROUND: The impact of chronic spontaneous urticaria (CSU) on health-related quality of life (HRQoL) is widely held to be mainly influenced by disease activity and comorbidities. OBJECTIVE: To assess the correlation between disease activity and HRQoL impairment by using validated disease-specific instruments. METHODS: The Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) was translated into Greek and subsequently applied to 110 CSU patients along with the Dermatology Life Quality Index and the Urticaria Activity Score. After the validity and reliability of the Greek CU-Q2oL had been determined, we assessed the relation between disease activity and HRQoL impairment by computing correlations as well as by performing multiple regression analysis. RESULTS: Exploratory factor analysis revealed a six-scale structure of the Greek CU-Q2oL that explained 67.9% of its total variance. The internal consistency was satisfactory with Cronbach's α >0.7. Disease activity was the only predictor of quality of life impairment, but it only moderately correlated with the CU-Q2oL total score (r = 0.40, p < 0.0001). CONCLUSION: Our results suggest that there are additional factors to disease activity that are responsible for the pronounced reduction of HRQoL in CSU, and this supports the recommendation to assess and monitor both disease activity and quality of life in CSU patients.

A subset of histamine receptor ligands improve thermotolerance of the yeast Saccharomyces cerevisiae.

AIMS: Histamine interacts with the stress response in eukaryotes. This study investigated the effects of antihistamines on the heat shock (HS) response in yeast, thereby exploring their functions in a well-established histamine receptor (H(x) R)-free model. METHODS AND RESULTS: Stress response was evaluated by determining growth and viability of postlogarithmic phase grown yeast cultures after HS at 53°C for 30 min. The effects of H(x) R ligands were investigated following short- and long-term administration. The H(1) R antagonist dimethindene exerted dose-related antifungal actions, whereas the H(2) R antagonist ranitidine failed to elicit any effect. In contrast, the H(3/4) R and H(4) R ligands, thioperamide and JNJ7777120, respectively, induced the thermotolerant phenotype. The circumvention of thermotolerance by cycloheximide and the induction of Hsp70 and Hsp104 expression indicated the contribution of de novo protein synthesis in the adaptive process, likely directed towards alterations in Hsp expression. CONCLUSIONS: The data provide evidence for the differential function of H(x) R ligands in thermotolerance induction in yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: First demonstration of the action of antihistamines in the HS response in yeast. The work supports the potential H(x) R-independent functions of histaminergic compounds in fungal adaptation and stimulates research on the prospect of their exploitation in eukaryotic (patho)physiology.

The role of histamine H4 receptor in immune and inflammatory disorders.

Since its discovery at the beginning of the 20th century, histamine has been established to play a pathophysiological regulatory role in cellular events through binding to four types of G-protein-coupled histamine receptors that are differentially expressed in various cell types. The discovery, at the turn of the millennium, that the histamine H4 receptor is largely expressed in haemopoietic cells as well as its chemotactic properties designate its regulatory role in the immune system. H4 receptors modulate eosinophil migration and selective recruitment of mast cells leading to amplification of histamine-mediated immune responses and eventually to chronic inflammation. H4 receptor involvement in dendritic cell activation and T cell differentiation documents its immunomodulatory function. The characterization of the H4 as the immune system histamine receptor directed growing attention towards its therapeutic exploitation in inflammatory disorders, such as allergy, asthma, chronic pruritus and autoimmune diseases. The efficacy of a number of H4 receptor ligands has been evaluated in in vivo and in vitro animal models of disease and in human biological samples. However, before reaching decisive conclusions on H4 receptor pathophysiological functions and therapeutic exploitation, identification of genetic polymorphisms and interspecies differences in its relative actions and pharmacological profile need to be addressed and taken into consideration. Despite certain variations in the reported findings, the available data strongly point to the H4 receptor as a novel target for the pharmacological modulation of histamine-transferred immune signals and offer an optimistic perspective for the therapeutic exploitation of this promising new drug target in inflammatory disorders.

Protective effect of salicylates against hydrogen peroxide stress in yeast.

AIMS: To investigate the effects of salicylates in Saccharomyces cerevisiae exposed to oxidative stress induced by hydrogen peroxide (H(2)O(2)). METHODS AND RESULTS: Saccharomyces cerevisiae was cultured through to the postlogarithmic phase of growth. Stress was induced by the addition of 1.5 mmol l(-1) H(2)O(2) for 1 h, while N-acetyl-l-cysteine (NAC) and glutathione (GSSG) were used as control agents that affect the redox balance. Sodium salicylate, at 0.01-10 mmol l(-1)or acetylsalicylic acid, at 0.02-2.5 mmol l(-1) was administered at various times before hydrogen peroxide stress. Both agents conferred resistance to a subsequent hydrogen peroxide stress, similarly to the induction of the adaptive response observed upon pretreatment with NAC and GSSG. Sodium salicylate was more potent as a short-term, but not as a long-term pretreatment agent, compared to acetylsalicylic acid. CONCLUSIONS: Pharmacological pretreatment with salicylates resulted in dose related increases in cell survival, indicating the induction of the protective response in yeast. SIGNIFICANCE AND IMPACT OF THE STUDY: The possible role of salicylates in the modulation of the hydrogen peroxide stress response in eukaryotic cells address questions on the effects of these commonly used therapeutic agents in a number of disorders exhibiting an oxidative stress component.

The histamine H4 receptor antagonist JNJ7777120 induces increases in the histamine content of the rat conjunctiva.

OBJECTIVES: Although the H(4) receptor localisation in the eye is unresolved, this study aimed to investigate the effects of the H(4) receptor antagonist JNJ7777120 in a model of experimental conjunctivitis. METHODS: JNJ7777120, at 0.005-1 mmol/l, was instilled into the lower conjunctival fornix of normal and compound 48/80 (C48/80)-challenged eyes of male Wistar rats, in the absence or presence of 40 mg/ml disodium cromoglycate (DSCG). Conjunctival histamine content was quantified 20 min post-challenge. Statistical analyses were performed by ANOVA. RESULTS: JNJ7777120 increased dose-dependently (r = 0.784, p < 0.001) the conjunctival histamine content. In the C48/80-challenged eye no effect of the antagonist was observed. Co-administration of JNJ7777120 with DSCG resulted in a biphasic action of JNJ7777120, implying a competitive action of the two agents. CONCLUSIONS: These data suggest a functionality of the H(4) receptor in the rat eye and address questions on the localization and the role of the receptor in ocular inflammation.

Effect of histamine on the signal transduction of the AtoS-AtoC two component system and involvement in poly-(R)-3-hydroxybutyrate biosynthesis in Escherichia coli.

AtoS-AtoC two-component system acts directly on the atoDAEB operon transcription to regulate the biosynthesis of short-chain poly-(R)-3-hydroxybutyrate. This study sought to investigate the effect of histamine and compound 48/80 on the regulation of AtoS-AtoC two-component system in Escherichia coli K-12 MA255 (speC(-), speB(-)) and the isogenic E. coli strains BW25113 (atoSC(+)) and BW28878 (DeltaatoSC) transformed with plasmids carrying related genes. Histamine or compound 48/80 induced or tended to reduce atoC transcription, respectively, while neither compound showed any effect on atoDAEB operon transcription. Moreover, histamine down-regulated poly-(R)-3-hydroxybutyrate biosynthesis, whereas compound 48/80 up-regulated its biosynthesis, maximal induction being obtained in the presence of multiple copies of AtoS-AtoC. Interestingly, co-administration of histamine counteracted this inductive effect of compound 48/80. The reported data provide the first evidence for a differential modulator role of histamine and compound 48/80 on the AtoS-AtoC two-component system signaling in potentially pathogenic bacteria, leading to a new perspective on their symbiotic behavior.

Effect of the Hsp90 modulators on the heat-shock response in eukaryotic cells.

The possible role of the heat-shock protein 90 (Hsp90) complex on the heat-shock (HS) response in yeast using the Hsp90 inhibitors geldanamycin (GA) and 17-allylamino-17-demethoxygeldanamycin (AAG), and prednisolone and 17beta-estradiol as modulators was investigated. Following long- or short-term administration of the drugs, either alone or in combination, the response was determined as cell viability and growth after exposure to HS. Upon short-term preconditioning, both Hsp90 inhibitors conferred cycloheximide-dependent thermal resistance to the yeast cultures, while upon long-term treatment the induction of thermotolerance was confined only to AAG. Co-administration of prednisolone or 17beta-estradiol failed to significantly alter the response to Hsp90 inhibitors. However, since short-term incubation with prednisolone alone induced thermotolerance, increased the budding cell fraction and tended to reduce the adaptive response to GA, its effect on GA-induced thermotolerance is not yet explained. Generally, GA and AAG showed a comparable short-term action but a different long-term effect on the HS response in yeast; this response was not related to any regulation by prednisolone or 17beta-estradiol (while 17beta-estradiol was unable to modify the response, the action of prednisolone in both the stress response and the cell cycle was equivocal).

Nuclear translocation during the cross-talk between cellular stress, cell cycle and anticancer agents.

The function of many endogenous molecules in all eukaryotic cells depends on their subcellular localisation, being active when localized in one cellular compartment and inactive in another. Translocation or re-localization of mislocalized components in the optimal subcellular site may contribute to the development of novel cancer therapies and to the re-evaluation of conventional treatment. For instance, various agents are able to entrap cytoplasmic anti-apoptotic pathways to the nucleus, thus activating apoptosis. Moreover, amongst the factors identified so far, the optimal location of the tumor suppressor p53 for promoting cell arrest and apoptosis seems to be the nucleus, while the nuclear factor kappa B (NFkappaB) is desirable to stay in the cytoplasm. Thus, the mechanisms of nuclear translocation of endogenous signaling components, like p53, NFkappaB and various heat shock proteins (HSPs), may serve as targets for pharmacological intervention, without excluding the possible role of uptake and active transport into the nucleus of extracellular proteins.

Chemotherapy: induction of stress responses.

Eukaryotic cells, from yeast to mammals, respond and adapt to environmental and microenvironmental stressors by evolutionary conserved multicomponent endogenous systems that utilise a network of signal transduction pathways to regulate the adaptive and protective phenotype. The balance between cell survival and cell death is decisive for sensitivity or resistance to DNA-damaging chemotherapeutic agents. Anticancer drugs may themselves act as stressors to induce adaptive signals that could limit their clinical value. Related research has been focused on the modulation of the expression and function of the heat shock proteins, the unfolded protein response, the mechanisms of subcellular translocation of signalling components, the genomic and non-genomic actions of drugs and endogenous functional components like hormonal pathways, the input of inflammation and alterations in the microenvironmental milieu and on the control of the cell cycle and proliferation. The outcome seems to be driven by the first-line responses that support cellular integrity and by specific mechanisms that depend on the type of cell and the nature, and duration and severity of the noxious stimulus. Data obtained from experimental organisms like the yeast have added valuable information on the basic conservation in cellular stress-related processes in eukaryotes and on the consequences that may accompany the adaptive and protective phenotype during the stress response to anticancer agents. Understanding the complex molecular pathways mediating these processes has started to contribute to the reevaluation of the current therapeutic regiments and to revolutionise the approaches for improved anticancer therapy.

Leukotriene antagonists attenuate late phase nitric oxide production during the hypersensitivity response in the conjunctiva.

OBJECTIVE: To investigate the role of cysteinyl leukotrienic (cysLT) antagonists on conjunctival nitric oxide (NO) release in experimental allergic conjunctivitis. METHODS: Zafirlukast, disodium cromoglycate or levocabastine were instilled into the C48/80-challenged eyes of male Wistar rats. The conjunctival histamine content and nitrite levels in the lavage fluid were quantified 45 min and 6 h post-challenge, respectively. Instillation of phosphate buffer saline reflected control treatment. Statistical analyses were performed by ANOVA. RESULTS: Topical challenge with C48/80 significantly altered the histamine and nitrite levels to 44.6 +/- 2.8% and 233 +/- 19% of the control (P < 0.01), respectively. Instillation of zafirlukast, disodium cromoglycate or levocabastine reversed the effect of C48/80 on nitrite release, its levels being 150 +/- 27%, 54 +/- 14% and 121 +/- 20% of the control (P > 0.05), respectively. Zafirlukast had no effect on the histamine content. CONCLUSIONS: By inhibiting the late-phase NO component of the conjunctival hypersensitivity response, cysLT antagonists might contribute to the management of ocular inflammatory responses.