Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases.

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.

Eosinophil-induced prognosis improvement of solid tumors could be enabled by their vesicle-mediated barrier permeability induction.

Eosinophils are multifunctional cells, which contain and produce many biologically active substances. Generally, eosinophilia is associated with parasitic infections or allergic disorders, while according to recent studies eosinophil infiltration is also present in target tissues of both physiological and pathological processes, such as angiogenesis, embryogenesis, immune regulation, different infections or neoplasies, leading to tissue damage or remodeling. Reflecting on prognosis improvement in the case of solid tumors after eosinophilic infiltration of their capsules, it could be hypothesized that eosinophils are not tumoricidal per se; rather they can perforate such barriers through their vesicles' content, whereas the tumoricidal cytokines such as interleukin 4 (IL-4) fulfill the tumoral necrosis. This scenario can be supported by the fact that IL-4 originated from macrophages and lymphocytes fails to mediate tumor necrosis in vitro conditions in absence of eosinophils. In addition, the requirement of eosinophil-mediated increasing permeability among diverse biologic barriers and tissues may explain the eosinophils' introduction in capsules of cysts, mucosal membrane of respiratory and gastroenteric systems, hemato-encephalic barrier, in embryos, as well as in bacterial and parasitic membranes. Thus, in some situations rather than being multifunctional effectors per se, eosinophils, due to induction of target barrier dysfunction, may assure the host-required action, mediated by various kinds of leucocytes and their biologic effectors. Consequently, a better understanding of physiology and patho-physiology of this enigmatic cell will lead to new clinical strategies.

From latent incubation launched into hostile symptomatic pathology: A probable survival strategy for common respiratory infectious agents.

Common respiratory infections usually show a latent incubation period, followed by an acute stage. Finally, due to new synthesis of specific antibodies, the relative microorganisms undergo a massive eradication from hostile organism. Meanwhile, clinical symptoms induced by innate immunity mechanisms during these pathologies are assumed properly as host attempts for the expulsion of infectious agents. Some studies have demonstrated the existence of immuno-modulatory abilities by different infectious agents, which can inhibit inflammatory response and the development of respective symptoms by hostile organisms, especially during incubatory period. In contrast, after the incubatory period microorganisms-induced immuno-inhibitory effects may undergo a reduction, and in the meantime clinical symptoms appear a few days before the hostile organism synthesizes specific antibodies, which can eradicate these pathogens. From the evolutionary viewpoint of microorganisms, maybe induction of pathologic symptoms even before the period of specific hostile antibody synthesis, but not at beginning of infection, could play a particular adaptive role. Such scenario first could assure a maximal multiplication for the infectious agents, whereas later attempts to support the host abandonment, even due to induction of clinical expulsive symptoms. The existence of related pathologies since ancient times leads to the suggestion that perhaps the induction of such diseases is not a purpose per se for such pathogens, but rather an instrument to provide for host abandonment on time to catch a next one, assuring therefore maximal successive reproduction.

Erratum to: Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

[This corrects the article DOI: 10.1186/s13601-016-0095-x.].

Favorable hymenoptera sting reactions during childhood may have enabled transmission of responsible allergic genotype into generations.

Allergic reactions caused by hymenoptera venoms represent a major medical problem for certain groups of population. In addition to different anaphylaxis reactions, less frequent fatal cases have been recorded in Europe and USA. It has been observed that generally, following the initial anaphylaxis reaction to the venom of such insects, milder and less frequent successive reactions occur in children than in adults, though the latter are less frequently stung. Such findings could be explained by the fact that mainly children may have the advantage of self-restraining the aggravation of further reactions due to the ability of a higher plasticity of immune and non-immune protective mechanisms or the ability of adjustment of regulatory autonomous vital systems, activated after a prior allergic reaction. Hypothetically such ability has enabled most of those individuals to reach at least major age and frequently have their successors. This way the genetic lines carrying the respective allergic phenotype might have been transmitted generation after generation, although the prior allergic generations lacked modern treatment of anaphylactic reactions.

Regulator Versus Effector Paradigm: Interleukin-10 as Indicator of the Switching Response.

The interleukin-10 (IL-10) is generally considered as the most important cytokine with anti-inflammatory properties and one of the key cytokines preventing inflammation-mediated tissue damage. In this respect, IL-10 producing cells play a crucial role in the outcome of infections, allergy, autoimmune reactions, tumor development, and transplant tolerance. Based on recent findings with regard to the mentioned clinical conditions, this review attempts to shed some light on the IL-10 functions, considering this cytokine as inherent inducer of the switching immunity. While acute infections and vaccinations are associated by IL-10 enhanced during few weeks, chronic parasitoses, tumor diseases, allergen-specific immunotherapy, transplants, and use of immune-suppressor drugs show an increased IL-10 level along months or years. With regard to autoimmune pathologies, the IL-10 increase is prevalently observed during early stages, whereas the successive stages are characterized by reaching of immune equilibrium independently to disease's activity. Together, these findings indicate that IL-10 is mainly produced during transient immune conditions and the persistent IL-10-related effect is the indication/prediction (and maybe effectuation) of the switching immunity. Actual knowledge emphasizes that any manipulation of the IL-10 response for treatment purposes should be considered very cautiously due to its potential hazards to the immune system. Probably, the IL-10 as potential switcher of immunity response should be used in association with co-stimulatory immune effectors that are necessary to determine the appropriate deviation during treatment of respective pathologies. Hopefully, further findings would open new avenues to study the biology of this "master switch" cytokine and its therapeutic potential.

Epidemiological, clinical and therapeutic aspects of cerebral malaria imported in Albania.

This is a case-report of two patients with cerebral malaria (CM) imported from West-African countries. Notably, this form of malaria was developed as a second disease episode, while the first episode was experienced in West Africa. These findings suggest that the second episode of malaria was caused by a different strain of Plasmodium falciparum as compared to the first one. They are the first cerebral malaria cases imported in Albania after the eradication and absence of Plasmodium for five decades. Early treatment of cerebral malaria is decisive on the duration of coma and disease's outcome.

Allergen immunotherapy for insect venom allergy: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Management of Insect Venom Allergy. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recomendations for EAACI's Guidelines on AIT.

Substance P expression in TRPV1 and trkA-positive dorsal root ganglion neurons innervating the mouse lung.

In the present study, the co-localisation of substance P (SP) with the vanilloid receptor TRPV1 and the neurotrophin receptor tyrosine kinase trkA was analysed in airway-specific murine dorsal root ganglion (DRG) neurons. DRG neurons labelled with Fast Blue were predominantly found at the segmental levels T2-T5. Immunoreactivity for the receptor TRPV1 was localized to 12% of Fast Blue labelled DRG neurons. Double-labelling immunohistochemistry revealed that a substantial number of them also co-express SP (7.6 +/- 1.1% (mean +/- S.E.M.)), whereas neurons with immunoreactivity for TRPV1 only were found in 4.4 +/- 1.3% of the retrogradely labelled neuronal population. Further analysis of retrogradely labelled neurons showed that their majority expressed trkA (62.8 +/- 1.4%), neurofilament protein 68-kDa (64.8 +/- 1.5%) or glutamate alone (19.5 +/- 1.9%). SP was always expressed in trkA-positive neurons. Based on the extent of co-localization of SP with the receptors TRPV1 and trkA in DRG airway neurons, the present study indicates that the DRG pathway may have effects on the magnitude of neurogenic inflammation in airway diseases such as asthma.

Specific immunotherapy in Albanian patients with anaphylaxis to hymenoptera venoms.

BACKGROUND: Severe allergic reactions during rush-specific immunotherapy (Rush-SIT) may occur in the treatment of hymenoptera sting allergy. The objective of the present study was to examine the characteristics of allergic reactions during Rush-SIT in a cohort of patients with allergy towards hymenoptera venom in the mediterranean population of Albania. METHODS: A retrospective study was performed using the clinical reports of 37 patients with venom of bee (apinae), wasp (vespidae, subfamily vespinae) or paperwasp (vespidae, subfamily polistinae) allergy treated with Rush-SIT between 1987 and 1996. After hymenoptera sting allergy diagnosis according to anamnesis and intracutaneous tests the patient were treated with Rush-SIT. The protocol lasted 3 - 4 d with an increase in the concentration from 0.01 microg/ml to 100 microg/ml. Anaphylactic reactions were classified according to the Mueller-classification. RESULTS: The frequency of reactions during Rush-SIT for bee-venom was 4.7% and for wasp-venom was 1.5% (p < 0.01). The mean frequency of reactions of Mueller grade II for the bee-venom Rush-SIT patients during the first 4 d (= 26 injections) was 0.73 and for the wasp-venom Rush-SIT patients 0.15. No patient experienced a third-degree reaction. 94.6% of the patient supported an end dose of 100 microg. CONCLUSIONS: Rush-SIT is a reliable method for the treatment of anaphylactic reactions to hymenoptera venom even in less developed countries. Bee-venom Rush-SIT was found to cause higher numbers allergic reactions than wasp or paperwasp Rush-SIT.

Unusual reactions to hymenoptera stings: what should we keep in mind?

This review includes a variety of extremely rare and unusual hymenoptera sting (HS) circumstances with regard to sting localization, geographic region, massivity of multiple stings, and particularly related to clinical symptoms. Such reactions occur in a temporal relationship to HS (s), differ from typical allergic symptomatology, and sometimes need follow-up during many months. With respect to pathogenesis, the major mechanisms involved are toxic, autoimmune, and other delayed immunological ones. While delayed inflammatory symptoms of the nervous system are considered as delayed hypersensitization or autoimmune entities, generalized rhabdomyolysis and consecutive acute kidney injury is considered a toxic reaction, mostly induced by massive envenomation to wasps or "Africanized" bees. Hemorrhagic episodes of targeted organ (s) could be additional potential risk for acute kidney injury, while the bee venom-induced hemorrhage is proposed to be a nonimmune-mediated anaphylactic symptom. The hemodynamic involvement of vital organs and systems with hypoxia and hypovolemia together with simultaneous immunoglobulin E (IgE) sensitization are considered potential indications for venom immunotherapy. In contrast, patients who have experienced various complications with unknown or nonallergic mechanisms should be informed about the importance of epinephrine's use and additional measures on future sting avoidance. In conclusion, although unusual reactions are extremely rare, it is important to keep them in mind.

Gliadin allergy manifested with chronic urticaria, headache and amenorrhea.

Gluten intolerance is an autoimmune enteropathy caused by heterogeneous mixture of wheat storage proteins. Malabsorption symptoms imply diarrhoea, abdominal pain/bloating and weight loss. This case describes a 22-year-old female subject, who had chronic headache, joint pain, urticaria and long period of amenorrhea. Skin prick tests revealed a sensitisation to α-gliadin, while neurological, gynaecological, endocrine and clinical-laboratory examinations did not justify the above-mentioned symptoms. Gluten-free diet resolved chronic symptoms and re-established the menstrual cycle, whereas a temporary gliadin daily diet re-exacerbated all clinical symptoms. Urticaria occurred 20 min and the chronic headache the next day after exposure to the gliadin-rich diet. In addition, the missing of the expected menstrual bleeding was observed. This case demonstrates that gliadin intake can induce malabsorption and 'idiopathic' neuronal or gynaecological symptoms.

Parasites induced skin allergy: a strategic manipulation of the host immunity.

UNLABELLED: The absence of a consistent link between parasitoses and skin allergic symptoms in the clinical investigations contrasts to the fact that some parasites are the most potent inducers of immunoglobulin E that exist in nature. To shed some light into this question, this review is focused on the actual knowledge regarding parasites life cycle, interactions with host immunity, the influence on host behavior, and finally the role of all these factors on the skin allergy. The collected data demonstrate that parasites could manipulate the host behavior for its own benefit in different ways, altering its (epi)genetic, biochemical, immunologic or physiologic functions as well as altering its behavior and activity. In this context, skin allergy may be associated with certain stages of the parasites' life cycle and migration into biological barriers, but not necessarily with presence of the parasitosis in the host organism. As compared to T helper (Th) 1 response, the Th2 one, the eosinophilic infiltration and the complement inhibition could assure better conditions for the development of some parasites. Taken together, the suggested hypotheses could be a plausible explanation for the epidemiological puzzle regarding urticaria occurrence, Th2 response and parasitoses, but further studies are necessary to provide better-based conclusions. KEYWORDS: Eosinophilic Infiltration; Host behavior; Parasites life cycle; Skin allergy; Th1/Th2 response.

Dexamethasone efficacy on bacterial meningitis--a retrospective analysis of Albanian adult patients.

BACKGROUND: Research on the effects of corticosteroids in bacterial meningitis (BM) yielded conflicting results. While some studies reveal that corticosteroids improve the outcomes in BM treatments, others provide strong evidence that patients do not profit from this treatment. We investigated the factors that may impact the dexamethasone efficacy in patients with BM. METHODOLOGY: In this retrospective study, we analyzed the medical records of patients with probable acute bacterial meningitis hospitalized between 2002 and 2008 at the Infectious Diseases Department, University Hospital Centre "Mother Theresa" of Tirana, Albania. They were all treated with dexamethasone. For study purposes, patients were divided into two subgroups: 1) Severely ill patients (Glasgow Coma Scale [GCS] or= 13. RESULTS: Sixty-seven patients analyzed had a mean age of 43.8 +/- 17.0 years old, forty-five (67.2%) of whom were males. The mean recovery time (RT) was 3.5 +/- 1.3 days, and four (6%) died. In the severely ill subgroup (GCS

A case of isocyanate-induced asthma possibly complicated by food allergy after peanut consumption: a case report.

BACKGROUND: Isocyanates are extensively used in the manufacture of polyurethane foams, plastics, coatings or adhesives. They are a major cause of occupational asthma in a proportion of exposed workers. Recent findings in animal models have demonstrated that isocyanate-induced asthma does not always represent an IgE-mediated sensitization, but still a mixed profile of CD4+ Th1 and TH2, as well as a CD8+ immune response. Despite immunologic similarities between this pathology and IgE-mediated food allergies, this co-morbidity is rarely reported. CASE PRESENTATION: A 50-year old man employed as vehicle body painter, for 8 years complained about breathlessness, wheezing, sneezing, nasal obstruction and excessive production of mucus during the use of DuPont Refinish Centari Tintings - an acrylic enamel tint. Symptoms occurred 15-20 minutes after workplace exposure and usually persisted until evening, or at times, up to two consecutive days. The above mentioned symptoms were associated with a decrease of lung functions parameters. The use of inhaled adrenergic bronchio-dilatators and steroids relived the symptoms.In addition, three years ago he developed an anaphylactic reaction due to peanut consumption, experiencing urticaria, angioedema and airway obstruction. He was successfully treated in the hospital. Later, the subject exhibited labial itching, as well as orbital and perioral angioedema, 20 minutes after stationary performance of challenge test with peanuts.Evaluating the reported data, this process might be developed rather due to induction of a TH2 profile, because in both cases have occurred IgE-mediated symptoms. A less plausible mechanism could be the presence of isocyanates in peanuts due to a probable contamination by pesticides resulting in an allergic reaction after "consumption" of di-isocyanate as long as the isocyanate contamination of peanuts has not been proven. CONCLUSION: Despite the lack of relevant laboratory findings, this might be the first case of isocyanate-induced occupational asthma described in a patient who developed peanut allergy symptoms later in his life. However, in order to take further suitable precautions, further studies are necessary to elucidate the questions posed in this report.