The use of phage display systems to combat infectious diseases in poultry: diagnostic, vaccine, and therapeutic approaches.

Development of molecular biology and understanding structures and functions of various biological molecules and entities allowed to construct various sophisticated tools for different biotechnological, medical, and veterinary applications. One of them is the phage display technology, based on the possibility to create specific bacteriophages bearing fusion genes, which code for fusion proteins consisting of a phage coat protein and a peptide of any amino acid sequence. Such proteins retain their biological functions as structural elements of phage virions while exposing foreign peptide sequences on their surfaces. Genetic manipulations allow to construct phage display libraries composed of billions of variants of exposed peptides; such libraries can be used to select peptides of desired features. Although the phage display technology has been widely used in biotechnology and medicine, its applications in veterinary and especially in poultry science were significantly less frequent. Nevertheless, many interesting discoveries have been reported also in the latter field, providing evidence for a possibility of effective applications of phage display-related methods in developing novel diagnostic tools, new vaccines, and innovative potential therapies dedicated to poultry. Especially, infectious diseases caused by avian viruses, bacteria, and unicellular eukaryotic parasites were investigated in this field. These studies are summarized and discussed in this review, with presentation of various possibilities provided by different phage display systems in development of useful and effective products facilitating management of the problem of infectious diseases of poultry.

Differences in the detection of circulating Hsp90 alpha between patients with atopic dermatitis and dermatitis herpetiformis.

Heat shock protein 90 alpha (Hsp90α) is one of the key intra- and extracellular chaperones responsible for the biological activity of various signaling molecules that are involved in (auto)immune-mediated inflammatory diseases. Recent epidemiologic data suggest that patients with atopic dermatitis (AD) are at risk for several autoimmune diseases, including dermatitis herpetiformis (DH), an extraintestinal manifestation of celiac disease (CD). In addition, pruritic diseases such as AD may be confused clinically with DH. In this study, we aimed to determine the role of circulating Hsp90α in patients with AD in relation to patients with DH, CD, and healthy controls. Using an enzyme-linked immunosorbent assay, levels of circulating Hsp90α were determined in serum samples derived from patients with AD (n = 31), DH (n = 26), CD (n = 15), and healthy controls (n = 55). Although serum concentrations of Hsp90α were similar between patients with DH, CD, and healthy controls, we found that serum levels of Hsp90α were significantly higher (mean value of 5.08-fold; p < 0.0001) in patients with AD when compared to patients with DH. A cutoff value calculated as 2 × standard deviation above the mean concentration of Hsp90α in DH patients revealed that 83.9% (26/31) of AD patients were Hsp90α positive, whereas none of the DH patients (0/26) displayed such a positivity. This preliminary study suggests a distinct role for extracellular Hsp90α in the pathogenesis of AD compared to DH and its potential use in distinguishing AD from DH. Nevertheless, the potential role of the evaluation of extracellular Hsp90α for distinguishing between AD and DH is at present speculative and requires further and careful observations.

Functional assessment of the right ventricle in patients with bronchial asthma of various severity.

INTRODUCTION: Pulmonary artery hypertension and its consequences still constitutes an underestimated clinical problem in asthma patients and its non-invasive early detection may influence proper treatment. AIM: To non-invasively examine the pulmonary artery flow parameters and right ventricular function in patients with asthma of various severity. MATERIAL AND METHODS: The analysis of parameters of echocardiography and first-pass and gated radionuclide angiography, and baseline examination in 31 patients with bronchial asthma and 16 healthy controls. RESULTS: Patients with severe asthma had higher mean pulmonary artery pressure (MPAP) compared to the healthy controls. The subgroup analysis of patients who suffered from asthma in their childhood showed that individuals with severe asthma were characterized by significantly higher MPAP than those with the mild/moderate condition (19.16 ±7.51 mm Hg vs. 5.0 ±1.15 mm Hg, p = 0.025). Gated, but not first-pass, radionuclide angiography revealed that individuals with severe asthma were characterized by a lower right ventricular ejection fraction (RVEF). Further analysis of the subgroup of patients in whom the initial manifestation of dyspnoea occurred no earlier than 6 years prior to the study showed that the RVEF of individuals with severe asthma was significantly lower compared to those with mild/moderate asthma (39.8 ±4.79% vs. 51.4 ±8.65%, p = 0.019). CONCLUSIONS: The pulmonary artery pressure in patients with severe asthma is significantly higher than in healthy individuals; in contrast, these two groups did not differ significantly in terms of the right ventricular echocardiographic characteristics. Gated radionuclide angiography, but not the first-pass technique, allowed for the detection of subtle right ventricular ejection fraction changes in asthma patients.

The effect of chronically occluded coronary artery recanalisation on baroreflex sensitivity and left ventricular systolic function.

BACKGROUND: Recanalisation of chronic total occlusion (CTO) of a coronary artery can be reflected by improvements in various clinical parameters. Revealing increased parasympathetic activity would constitute an additional argument for performing this procedure. AIM: To assess the effect of CTO recanalisation on baroreflex sensitivity (BRS) and left ventricular ejection fraction (LVEF) in stable symptomatic patients with coronary artery disease. METHODS: BRS (spectral analysis, transfer function, Blackman-Tukey algorithm, 0.03 Hz bandwidth Parzen window) and LVEF (echocardiography, Simpson's method) were analysed in 23 patients: one day (R1) before, one day (R2) after, and three months (R3) after CTO recanalisation. Patients were divided into two groups: those with depressed (≤ 3 ms/mm Hg) or preserved(> 3 ms/mm Hg) BRS. RESULTS: Significant BRS changes were observed in the study group compared to baseline values (p = 0.016). In the patients with a depressed reflex, BRS in R2 was similar to R1 and almost doubled in R3 (p = 0.018). In the patients with a preserved reflex, BRS significantly decreased in R2 (p = 0.024) and returned to the baseline value in R3. The behaviour of LVEF was homogenous in the groups, showing an increase from R1 to R3. CONCLUSIONS: The improvement in autonomic nervous system activity after successful CTO recanalisation is reflected by an increase in BRS, and the changes are dependent on the baseline value of the measurement: patients with a depressed BRS before recanalisation present a greater BRS improvement than patients with a preserved BRS. The CTO recanalisation leads to the improvement of LVEF in both groups.

Application of adjusted subpixel method (ASM) in HRCT measurements of the bronchi in bronchial asthma patients and healthy individuals.

BACKGROUND: Recently, we described a model system which included corrections of high-resolution computed tomography (HRCT) bronchial measurements based on the adjusted subpixel method (ASM). OBJECTIVE: To verify the clinical application of ASM by comparing bronchial measurements obtained by means of the traditional eye-driven method, subpixel method alone and ASM in a group comprised of bronchial asthma patients and healthy individuals. METHODS: The study included 30 bronchial asthma patients and the control group comprised of 20 volunteers with no symptoms of asthma. The lowest internal and external diameters of the bronchial cross-sections (ID and ED) and their derivative parameters were determined in HRCT scans using: (1) traditional eye-driven method, (2) subpixel technique, and (3) ASM. RESULTS: In the case of the eye-driven method, lower ID values along with lower bronchial lumen area and its percentage ratio to total bronchial area were basic parameters that differed between asthma patients and healthy controls. In the case of the subpixel method and ASM, both groups were not significantly different in terms of ID. Significant differences were observed in values of ED and total bronchial area with both parameters being significantly higher in asthma patients. Compared to ASM, the eye-driven method overstated the values of ID and ED by about 30% and 10% respectively, while understating bronchial wall thickness by about 18%. CONCLUSIONS: Results obtained in this study suggest that the traditional eye-driven method of HRCT-based measurement of bronchial tree components probably overstates the degree of bronchial patency in asthma patients.

[The comparison of selected spirometric parameters with functional muscles exercise evaluation in patients with myasthenia]. / Porównanie wybranych parametrów spirometrycznych z funkcjonalna ocena wysilkowa miesni u chorych na miastenie.

UNLABELLED: Pathological skeletal muscle weakness is an axial clinical symptom of myasthenia (MG). Diminished respiratory muscular force can be manifested by decreased peak expiratory flow (PEF) value. MATERIAL AND METHODS: Patients aged 13-77 years were studied at which according to Osserman classification ocular form (the type I) or generalized form (the type II) was diagnosed (n = 68). PEF and FVC values such as % of predicted value (PV) obtained in "flow-volume" measure were analysed. The trunk and extremities muscles force was estimated according to Besinger. RESULTS: Weakness of lower extremities muscles was found at all examined subjects. Positive result of trunk muscle test was found in 69% of patients with type I and 89% with type II. In type II upper extremities muscles (UEM) weakness was observed more often than in type I (74% subjects vs. 31%). In both types of MG the mean value of PEF was lower in patients with UEM weakness and amounted 89.5% vs. 112.4% in type I and 87.4% vs. 100.4% in type II. In type I the mean value of FVC was lower in patients with UEM weakness than in patients without symptoms (83.7% vs. 106.2%), with trunk muscles weakness (93.8% vs. 111.7%) and in patients with decreased muscles force up to 15% (87.5% vs. 106.7%). In this type of MG decreased value of FVC < 80% PV was observed in 50% of patients with UEM weakness and in 40% of patients with decreased muscles force up to 15%, but at none of subjects without symptoms in above tests. CONCLUSIONS: In patients with myasthenia of type I and II the weakness of upper extremities muscles correlates with decreased PEF value in spirometry. In addition in ocular myasthenia decreased FVC value was observed more often in patients with positive results of test of the functional muscles estimation.

Asthma control in patients with asthma and allergic rhinitis receiving add-on montelukast therapy for 12 months: a retrospective observational study.

BACKGROUND: Montelukast, a potent leukotriene receptor antagonist, is approved for treatment of both asthma and allergic rhinitis (AR). No studies to date have examined whether montelukast can improve asthma control over a long period of time in patients with seasonal AR and asthma. OBJECTIVE: To evaluate asthma control and use of asthma-related medical resources by patients with inadequately controlled mild to moderate persistent asthma and seasonal AR who required addition of montelukast as part of routine care. METHODS: This multicenter, 24-month, pre-post retrospective observational study included patients receiving current inhaled corticosteroid (ICS) therapy (alone or in combination with long-acting beta-agonist [LABA]), who received add-on treatment with montelukast for 12 consecutive months. The incidence of asthma attacks, defined as emergency department visit, hospitalization, or oral corticosteroid use for asthma, was compared for the year before and the year after addition of montelukast to therapy. RESULTS: For the 696 patients from Italy, Poland, and Spain who were included in the analyses, the proportion of patients experiencing an asthma attack declined from 31.5% in the year before to 10.1% (p < 0.001) the year after addition of montelukast to therapy. Proportions of patients with an asthma-related emergency room visit, hospitalization, and oral corticosteroid use declined from 18.7% to 3.9%, from 5.2% to 1.4%, and from 17.5% to 5.9% (all p < 0.01), respectively. The incidence of these outcomes declined in all three countries, regardless of baseline asthma severity or asthma therapy (ICS alone or ICS + LABA). Important study limitations include the possibility of selection bias or missing medical chart data in this retrospective study design. Also noteworthy is the inclusion of only those patients who remained persistent with montelukast therapy. Therefore, the results of the study are relevant for patients who remain persistent with montelukast therapy. CONCLUSIONS: Addition of montelukast to current ICS therapy improved long-term asthma control and resulted in substantial reductions in asthma-related resource use by patients with mild or moderate persistent asthma and concomitant seasonal AR who were persistent with montelukast therapy in this retrospective observational study.

[Spirometric evaluation of lung function in patients with myasthenia]. / Spirometryczna ocena funkcji pluc u chorych na miastenie.

UNLABELLED: Effort dyspnoea or dyspnoea at rest are predominating among subjective complaints in patients with myasthenia (myasthenia gravis--MG). THE AIM of the study was to evaluate the airway function in patients with MG by means of the chosen spirometric parameters analysis. MATERIAL AND METHODS: We observed 68 patients with MG in which type I (the ocular myasthenia), type IIA (the mild generalized form), type IIB (the subacute generalized form) and type IIC (the acute generalized form) was diagnosed based on Osserman classification and on 20 healthy volunteers (control group--CG). The function of the airways was assessed by means of "flow-volume" spirometry. RESULTS: The mean values of FEV1, MEF25-75 i FVC in the type II MG were lower than in CG. The mean value of PEF in the type II was lower than in CG and lower than in type I. In the type I of MG the mean values of evaluated parameters were not different than in CG. Decrease of PEF value was the most often found. The frequency of decreased PEF and FEV1 values was higher in type II than in CG. In all types of generalized MG the reduced FVC was found more frequently than in healthy people. In each types of MG (the type IIA, IIB, IIC) the mean values of the estimated parameters and the frequency of the deviation from predicted values were not different. CONCLUSION: The results show that in type II of MG the decrease of spirometric parameters is observed more often than in healthy people and these abnormalities are most marked in PEF. In the ocular MG the distinct tendency to FVC decrease is observed.

[Pulmonary masks of achalasia cardiae]. / Maski plucne achalazji przelyku.

In this article, the literature regarding the effects of achalasia cardiae on pulmonary disorders is reviewed. We specifically focused on the issue how achalasia may be associated with: airway obstruction, stridor, cough and recurrent pneumonia. Authors suggested it is necessary to carry out full differential diagnosis considering achalasia cardiae in patients with unsatisfactory treatment of recurrent respiratory tract diseases.

[Pseudoasthmatic syndrome due to achalasia cardiae]. / Zespól pseudoastmatyczny maskujacy achalazje przelyku.

The authors present a case of an 18-year-old woman, were referred to an allergologist because of a suspicion of bronchial asthma. She had complained of respiratory symptoms: chronic bronchitis for three years, cough and dyspnoea. Auscultation revealed wheezies and rales. Spirometry showed severe airway obstruction. Because of negative result of a reversibility test, ex iuvantibus treatment with prednisone was used but no results were obtained. The next step of diagnostic procedure was computed tomography which revealed the trachea compression by the dilated oesophagus. Finally she was found by us to have esophageal achalasia. Pharmacological treatment with nifedipine did not give an improvement. After operation the asthmatic symptoms disappeared and marked improvement was found in the flow-volume curve and in the chest radiogram. The demonstrated case proves that esophageal achalasia should be considered as one of the differential diagnoses of pathological respiratory symptoms suggesting asthma difficult to treat.

[Nasal provocation tests with house dust mite in patients with perennial rhinitis]. / Prowokacje donosowe alergenami roztoczy kurzu domowego u chorych z calorocznym alergicznym niezytem nosa.

UNLABELLED: The aim of this study was to evaluate a response of the upper airways mucosae to allergens house dust mite: Dermatophagoides farinae and Dermatophagoides pteronyssinus. Compared were results of nasal challenge with results of skin prick tests. 87 patients with perennial rhinitis allergic to Dermatophagoides farinae and/or Dermatophagoides pteronyssinus were included. There were 58 men, 29 women, age 18-54 years, mean age 26 years. Nasal provocation tests were performed first with solvent, and next if flow rate did not change more than 20%, with Dermatophagoides farinae and Dermatophagoides pteronyssinus extracts. The nasal response was evaluated with active anterior rhinomanometry. Nasal flow was measured at 15, 30 and 45 minutes after allergen challenge. There were 99% positive skin prick tests Dermatophagoides farinae and 94% positive skin prick tests Dermatopagoides pteronyssinus. Nasal provocation tests with Dermatophagoides farinae extract were positive in 63% patients and Dermatophagoides pteronyssinus extract--in 62% patients. Majority of nasal challenges were positive at 15th minute. There is association between skin prick tests Dermatophagoides farinae and Dermatophagoide pteronyssinus 4+ and positive nasal provocation tests with the same allergen (p < 0.05). We have found correlation between skin tests Dermatophagoides farinae and Dermatophagoides pteronyssinus (correlation index = 0.58) and no correlation between nasal provocation Dermatophgoides farinae and Dermatophagoides pteronyssinus extracts. CONCLUSION: Nasal provocation tests are more specific than skin prick tests in patients with perennial rhinitis.

[Acarofauna in the apartments of patients with perennial atopic rhinitis and functional tests of the respiratory system]. / Akarofauna mieszkan chorych na caloroczne atopowe zapalenie blony sluzowej nosa a badania czynnosciowe ukladu oddechowego.

Prolonged exposure to house dust mites (HDM) of the Pyroglyphidae family leads to the development of perennial allergic rhinitis (PAR) in sensitized subjects. In PAR patients bronchial hyperreactivity--the clinical manifestation of allergic inflammation in the lower airways is often observed. The aim of the study was to estimate the influence of the exposure to HDM in PAR patients on selected functional parameters of the lower airways. The study was performed on 64 patients with PAR caused by allergy to HDM (Dermatophagoides pteronyssinus, Dermatophagoides farinae) without either symptoms of asthma or spirometry abnormalities. The lower airways function was estimated by bronchial histamine provocation test (BHR) and flow-volume spirometry. The house dust mite quantity was measured in dust samples collected in spring and autumn. One sample was assessed by flotation technique with the use of methylene chloride and the mites species were identified (direct method) and the other sample was used to perform the Acarex test (semiquantitative guanine determination test). Positive result of Acarex test was obtained in spring in 72% houses and in autumn in 63%. The predominance of the Pyroglyphidae family was observed in PAR patients' houses. The study showed that the exposure to the allergenic HDM in the quantity higher than 0.6 mg guanine/g dust in autumn implies the increased incidence of both bronchial hyperreactivity and decreased airflow in the small bronchi in control spirometry tests. A strict correlation between the quantity of mites in houses in spring and autumn measured by the direct (flotation method) and the indirect (Acarex) tests was observed. Both methods proved to be equivalent in detecting allergens of house dust mites.