Predictors of excessive short-acting ß2-agonist use and asthma exacerbations: a retrospective analysis of a Polish prescription database.

Introduction: Despite being linked to unfavourable outcomes, short-acting ß2-agonists (SABAs) are still overused by a substantial proportion of patients with asthma. Aim: To analyse the prevalence and predictors of SABA overuse and exacerbations in patients with asthma in a nationwide database of prescription purchase records. Material and methods: The prevalence of excessive SABA use (≥ 12 canisters) and overuse (≥ 3 canisters) was analysed among patients aged 18-64 years who purchased asthma medications in 2018. Predictors of excessive SABA use and SABA overuse were examined by quasi-Poisson regression. Negative binomial regression was used to study the association of excessive SABA use or overuse to the risk of asthma exacerbation defined as a prescription for oral corticosteroids. Results: Of 91,763 patients with asthma, 42,189 (46%) were SABA users (mean age, 47 years; 58% female). Among them, 34% purchased ≥ 3 SABA canisters, and 6% purchased ≥ 12 canisters. The risk (risk ratio, 95% CI) of excessive SABA use was lower in patients with concomitant prescriptions for inhaled corticosteroids (0.41, 0.34-0.48) or inhaled corticosteroids and long-acting ß2-agonists (0.52, 0.47-0.56), women (0.63, 0.58-0.68), and those in secondary care (0.60, 0.44-0.66); older age was associated with a higher risk of excessive SABA use (1.06, 1.03-1.10). Excessive SABA use was the strongest predictor of asthma exacerbations among all patients (3.24, 2.84-3.70) and in those with ≥ 1 exacerbation (1.60, 1.50-1.71). Conclusions: Excessive SABA use is highly prevalent in asthma management, is associated with lack of prescriptions for inhaled corticosteroids, and substantially increases the exacerbation risk.

Effect of Vitamin D Concentration on Course of COVID-19.

BACKGROUND The course of COVID-19 disease is associated with immune deregulation and excessive release of pro-inflammatory cytokines. Vitamin D has an immunomodulatory effect. We aimed to assess the possible correlation between the incidence and severity of SARS-CoV-2 infection and serum vitamin D concentration. MATERIAL AND METHODS A total of 505 successive patients admitted to a COVID-19-dedicated hospital were included in the retrospective analysis. Serum 25-hydroxyvitamin D (25-OHD) levels and SARS-CoV-2 RT-PCR throat swab test results were determined for each patient. The course of COVID-19 was assessed on the basis of the serum Vitamin Modified Early Warning Score (MEWS), which includes respiratory rate, systolic blood pressure, heart rate, temperature, and state of consciousness), as well as number of days spent in the intensive care unit (ICU) and need for oxygen therapy. RESULTS There was no difference in 25-OHD concentration between COVID-19-confirmed and negative results of the PCR tests. No correlation was found between serum 25-OHD in the COVID(+) group and the need for and time spend in the ICU, as well as the MEWS score. Multivariate analyses showed a positive correlation between need for oxygen therapy and lower 25-OHD concentration, as well as older age (P<0.001) and similar positive correlation between need for ventilation therapy with lower 25-OHD concentration, as well as older age (P=0.005). CONCLUSIONS Our findings do not support a potential link between vitamin D concentrations and the incidence of COVID-19, but low vitamin D serum level in COVID-19 patients might worsen the course of the disease and increase the need for oxygen supplementation or ventilation therapy.

Pru du 1, the Bet v 1-homologue from almond, is a major allergen in patients with birch pollen associated almond allergy.

Background: Almond allergy is common and can manifest in two different forms. Primary almond allergy has been reported to be associated with sensitization to almond legumin Pru du 6. In birchendemic regions, there is a link between birch-pollinosis which is likely based on a cross-reactive Bet v 1 homologue, a yet unidentified allergen in almond. Therefore, we sought to identify and characterize a Bet v 1-homologue in almond. Methods: The expression of a Bet v 1 homologue in almond kernels was confirmed by mass spectrometry. The recombinant protein was produced in Escherichia coli and its cross-reactivity and allergenic potency was analyzed by IgE quantitative and competitive ELISA, immunoblotting and basophil histamine release using sera from 17 almond allergic patients. Results: The identified Bet v 1 homologue received the designation Pru du 1.0101. Pru du 1.0101 bound IgE from 82 % of almond allergic patients. Bet v 1 was able to inhibit IgE-binding to rPru du 1 by 100%, while rPru du 1 inhibited IgE binding to rBet v 1 by 48%. Pru du 1.0101 activated basophils, though 100- to 1000-fold higher concentrations were required for maximum activation in comparison to rBet v 1. Conclusion: Considering the strong inhibition capacity and higher allergenic potency of Bet v 1, the results provide compelling evidence for primary sensitization to Bet v 1 in case of birch pollen associated almond allergy. Combining Pru du 6 and Pru du 1 in diagnostic approaches may help to discriminate between primary and birch-pollen associated almond allergy.

The Influence of the Type of Electrolyte in the Modifying Solution on the Protective Properties of Vinyltrimethoysilane/Ethanol-Based Coatings Formed on Stainless Steel X20Cr13.

The paper reports the results of the examination of the protective properties of silane coatings based on vinyltrimethoxysilane (VTMS) and ethanol (EtOH), doped with the following electrolytes: acetic acid (AcOH), lithium perchlorate LiClO4, sulphuric acid (VI) H2SO4 and ammonia NH3. The coatings were deposited on stainless steel X20Cr13 by the sol-gel dip-coating method. The obtained VTMS/EtOH/Electrolyte coatings were characterized in terms of corrosion resistance, surface morphology and adhesion to the steel substrate. Corrosion tests were conducted in sulphate media acidified up to pH = 2 with and without chloride ions Cl-, respectively. The effectiveness of corrosion protection was determined using potentiometric curves. It has been demonstrated that the coatings under study slow down the processes of corrosion of the steel substrate, thus effectively protecting it against corrosion.

Clinical Determinants of Successful Omalizumab Therapy in Severe Allergic Asthma Patients: 4-Year-Long, Real-Life Observation.

INTRODUCTION: Omalizumab is a high-cost therapy recommended for the treatment of severe allergic asthma. OBJECTIVE: To find clinical parameters that are related to the sustained response to omalizumab. PATIENTS AND METHODS: This retrospective, real-life, 4-year follow-up was provided in Poland between March 2013 and May 2019. The success of omalizumab was assessed based on composed subjective and objective criteria. Simple/multiple regression analyses were performed to search for predictors of the response to omalizumab. RESULTS: A total of 989 severe allergic asthma patients were referred for omalizumab therapy, of whom 854 patients were considered eligible for treatment. At weeks 16 and 52, omalizumab was successful in 84% and 91% of patients, respectively. Treatment effectiveness was maintained up to the 4-year follow-up. Four predictors of the response to omalizumab were found at week 16 and two at week 52. The results at week 16 may be used as predictors of success at week 52 based on the model including baseline FEV1% and change in ACQ-7 and miniAQLQ score at week 16: the area under the ROC curve equals 0.746 [95% CI: 0.672-0.820]. CONCLUSION: Omalizumab therapy is very effective, with this efficacy sustained after 4 years of treatment. Success of the therapy can be predicted from the baseline FEV1% and clinical improvement (based on ACQ-7 and miniAQLQ scores) at week 16.

The Reactions of H2O2 and GSNO with the Zinc Finger Motif of XPA. Not A Regulatory Mechanism, But No Synergy with Cadmium Toxicity.

Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (ZnXPAzf) with hydrogen peroxide and S-nitrosoglutathione (GSNO), as oxidative and nitrosative stress agents, respectively. We also used the Cd(II) substituted XPAzf (CdXPAzf) to assess the situation of cadmium assault, which is accompanied by oxidative stress. Using electrospray mass spectrometry (ESI-MS), HPLC, and UV-vis and circular dichroism spectroscopies we demonstrated that even very low levels of H2O2 and GSNO invariably cause irreversible thiol oxidation and concomitant Zn(II) release from ZnXPAzf. In contrast, CdXPAzf was more resistant to oxidation, demonstrating the absence of synergy between cadmium and oxidative stresses. Our results indicate that GSNO cannot act as a reversible modifier of XPA, and rather has a deleterious effect on DNA repair.

Clinical and economic impact of a one-year treatment with omalizumab in patients with severe allergic asthma within a drug programme in Poland.

BACKGROUND: Allergic asthma is the most prevalent phenotype of severe asthma where treatment with omalizumab (OMB) has been proven to be particularly beneficial. In Poland, OMB therapy is available and reimbursed within a drug programme where strict inclusion and exclusion criteria are defined. The objective of this study was to present a descriptive analysis regarding the trends in outcomes (clinical, quality of life, costs) among a cohort of patients who satisfy inclusion criteria for the initiation of OMB treatment and who successfully responded to OMB according to a set of objective criteria. METHODS: A retrospective analysis of data collected during the 52 weeks of OMB treatment was carried out. The study population was adolescents and adults with severe allergic asthma that was uncontrolled despite a combination of high-dose inhaled corticosteroids (ICS)/long-acting beta-agonists (LABA) and/or other controllers (leukotriene receptor antagonists (LTRA), sustained-release theophylline, and short- or long-acting muscarinic antagonists (SAMA/LAMA), who were the first to finish the one-year treatment. A clinical and cost analysis for patients included in the programme was conducted comparing the one-year pre-treatment period to the one-year treatment period outcomes. RESULTS: Data of 85 patients who completed the first year of therapy were reviewed and analysed. Add-on OMB treatment resulted in a median decrease in exacerbation rate of 66% relative to the baseline and a reduction in oral steroid (OCS) dose by an average of 7.7 mg. At the end of the 52 weeks of therapy the changes in the quality of life questionnaire (AQLQ) and the asthma control questionnaire (ACQ) scores were 1.86 and 1.45 points, respectively. The mean cost of asthma treatment increased by an average of 15,979 EUR per patient per year (baseline period - 802 EUR/patient/year; OMB treatment - 16,781 EUR/patient/year). The cost to avoid one exacerbation was 17721 EUR. CONCLUSION: The clinical outcomes for the observed subset of patients were highly improved. At the same time, costs of the treatment increased, mainly due to the high OMB costs. Other costs associated with a lower number of hospitalizations and ED and office visits and a reduction in OCS dose decreased. These descriptive data can be used for further investigation in defining patients who benefit the most from OMB treatment in clinical practice.

Recurrent infections in a patient with psoriatic arthritis and hypogammaglobulinemia, treated with conventional and biologic disease-modifying anti-rheumatic drugs-a primary or secondary entity?

A 54-year-old man with confirmed psoriatic arthritis, treated with conventional and biologic disease-modifying anti-rheumatic drugs, suffered from severe, recurrent respiratory tract infections. He was found to have hypogammaglobulinemia. Further investigations confirmed the diagnosis of common variable immunodeficiency. Introduction of immunoglobulin G replacement therapy allowed for safe and effective treatment of psoriatic arthritis with etanercept and methotrexate. Patients with a history of recurrent infections on disease-modifying anti-rheumatic drugs and hypogammaglobulinemia should be assessed for primary antibody immunodeficiencies, even in adulthood.

Sexual activity during pregnancy.

OBJECTIVE: Pregnancy is usually associated with significant regression in genito-genital intercourse frequency, sexual desire and satisfaction. The aim of the study was to determine women's sexual habits during the third trimester of gestation and to compare their sexual activity before the current pregnancy and during previous pregnancies in case of multiparas. MATERIAL AND METHODS: The study material consisted of women in the third trimester of pregnancy, recruited from the Outpatient Clinic of the 1st Department of Obstetrics and Gynecology, Medical University of Warsaw between January 2013 and February 2014, who filled out a self-prepared questionnaire. The questionnaire consisted of three parts: demographic data, sexual activity prior to current pregnancy and during gestation, including sexual positions and sources of knowledge regarding the subject. The survey involved 25 questions and was distributed among 220 patients, out of which 165 were returned and 149 properly filled out and analyzed. RESULTS: The average age of the respondents was 29.6 ± 4.85 years; the majority (78.8%) were in an uncomplicated pregnancy. The decrease in sexual activity was evident in all age groups--the majority usually had sex 1 to 3 times a month in contrast to 1-2 times a week prior to conceiving. Sexual activity decreased significantly with increasing age. The main reasons for abandoning sexual activity included: decreased libido (35.5%), the doctor's suggestion (29%) and fears concerning child's health (29%). During pregnancy the frequency of vaginal intercourse significantly decreased (100% prior to vs. 86.6% during pregnancy; p < 0.001); as did oral sex (44.3% vs. 29.5%; p = 0.043) and anal sex (12% vs. 5.4%; p = 0.02). 54% of the respondents declared reduced satisfaction with sexual life during pregnancy in comparison with the previous period; almost half (43.5%) felt less attractive while pregnant. The same claim was related to libido--it decreased in 58.8% of respondents. Multiparas tended to have sexual intercourses less often in consecutive pregnancies (41.2%) or with an equal frequency (35.3%). The main source of knowledge about sexual life during pregnancy listed by women included internet and other media (63.5%), while medical staff was mentioned by 30%. CONCLUSIONS: Sexual activity decreases during gestation, however, it often result from an increased fear for the child and lack of possibilities to confront and broaden the knowledge on this subject. The role of medical staff in consulting sexual activity problems is insufficient.

[The costs of asthma in Poland in 2012]. / Koszty astmy w Polsce w 2012 roku.

UNLABELLED: The costs incurred for treatment of patients with asthma are an important part of health care in the budget of each country. The aim of the study was to evaluate the direct and indirect costs of asthma in Poland. The study was based on questionnaires completed by professionals--allergists and pneumonologists of 13 centers in which is conducted the diagnosis and treatment of asthma. MATERIALS AND METHODS: The costs of asthma were determined from the payer perspective (NHF) and from the perspective of social security (ZUS). The study evaluated the direct costs of one patient with asthma in 2012, and indirect costs, as measured by human capital or friction costs. The study involved 128 people, including 84 women and 44 men, mean age 51.04+/11.41 years. RESULTS: Among the most frequent concomitant diseases: allergic rhinitis (93.75%), gastro-oesophageal reflux (38.54%), urticaria (16.67%), atopic dermatitis (21.88%) were present. The average monthly cost of drugs in 2012 amounted to PLN 251.32 (61.29 EURO, 2012 EURO 1 year=4.1 PLN), including patient,s copayment amounted to PLN 65.48 (EUR 15.97). The study showed that the direct cost per patient was 3240,88 PLN (790,46 EURO,). The Indirect cost, calculated using the human capital was for an average PLN 17,579.18 (4287.6 EURO) per patient, and using the method of friction costs was PLN 5974.06 (EUR 1,457.2). CONCLUSIONS: Estimating the cost of the disease often depends on the adopted method of analysis, but in the study group, a significant advantage of the indirect costs of the disease was observed. The effectiveness of the treatment of asthma in Poland should also be aimed at reducing the indirect costs of illness.

Epidemiology of asthma in Poland in urban and rural areas, based on provided health care services.

INTRODUCTION: Asthma is a serious health and social problem, also in Poland. The epidemiological data indicate that the problem of asthma concerns approximately 4 million people in Poland, whereas almost approximately 70% of them have no diagnosis and are not aware of their illness, and on the other hand in 39% of persons who declared the diagnosis of asthma in a survey the diagnosis was negatively verified (overdiagnosis of asthma). So far, no detailed comparative studies for asthma incidence rate in urban and rural areas were conducted in Poland. The aim of the study was to analyze patients with asthma in Poland in the years 2008-2012, with regard to province and type of commune (rural/urban). MATERIAL AND METHODS: The study used data from National Health Fund (NFZ) - reported by health care providers regarding the patients diagnosed with asthma. Using structured query language (SQL) a set of patients was selected and created, for whom at the same time ICD-10 code: J45.X-bronchial asthma was reported. In order to estimate the number of patients with asthma we used the PESEL social security number as a unique identifier of the patient. Code of the patient's commune of residence in conjunction with the Central Statistical Office data formed the basis for the division of municipalities into urban and rural areas. The analysis of asthma incidence trends in Poland was performed on the basis of health services provided to patients. The analysis was performed by using the Statistica 10 software using a negative binomial regression model. RESULTS: In 2009 a significant increase in the number of patients with asthma was observed compared with the previous year, whereas after 2009 the number of patients diagnosed with asthma remained relatively constant. A significant increase of predominance of women among asthma patients in recent years can be noticed: from 107% in 2008 to almost 115% in 2012 (F:M ratio). Regardless of the analyzed year and the diagnosis the incidence rate remained constant: approximately 55-57% for urban areas and about 43-45% in rural areas. CONCLUSIONS: The average prevalence rate for rural areas is significantly lower than for urban areas. The use of adjusted incidence rate leads to the conclusion that the number of sufferers in urban areas is higher (about 10%) of the number of sufferers in the rural areas. The results of the analysis are consistent with information from previous studies in Poland and in the world.

Sequence based typing and pre-absorption test in retrospective analysis of a pseudo-outbreak of Legionella infections differentiates true cases of legionellosis.

UNLABELLED: The aim of this study was elimination of false positive results obtained by the Chlamylege kit. Two serological kits (IgM ELISA L. pneumophila sgs1-7; ImmuView(TM) L. pneumophila sg1/sg3) and pre-absorption tests (with L. pneumophila sg1 and sg3 reference strains antigens) were used. 153 sera (79 patients) were examined. The high correlations were found between the results by both tests. Positive results by ELISA (sgs1-7) were found in 19/79 patients; by ImmuView(TM) (sg1+sg3) in 16/63. In 8 patients, the dynamics of the IgM in pairs of sera was high (ratio ≥2). In 5/8 of those patients seroconversion was determined. Selected pre-absorbed sera (15 pairs) were tested simultaneously by the same tests. In 8/15 pairs of sera, the reduction of IgM levels in pre-absorbed sera was higher than 10. The reduction of IgM differed in sg1 and sg3 tests. The probability of infections due to L. pneumophila sg3 (7 patients) and L. pneumophila sg1 (5 patients) was based on the results of pre-absorption tests. The correlation between ELISA and ImmuView(TM) tests of pre-absorbed sera was statistically significant (Po=0.0389). Moreover, genotyping of L. pneumophila (SBT) directly in the sera of selected 15 patients (high IgM reduction) was carried out. Completed 7 alleles profile (ST36) was determined in one patient. However, a second patient had the same profile of 5 alleles, and similar reactions in pre-absorption tests. At least 4 sources of infections were suggested on the base of genotyping and pre-absorption results. CONCLUSIONS: Positive results obtained by molecular techniques (eg.PCR) in the diagnosis of Legionella infections should be supplemented by other tests for confirmation of legionellosis. The sequence based typing carried out directly in clinical specimens seems to be a promising method.

[Clinical efficacy and costs of the three-year specific allergen immunotherapy--retrospective study]. / Skutecznosc i koszty trzyletniej immunoterapii alergenowo-swoistej--badanie retrospektywne.

UNLABELLED: Morbidity on allergic diseases has been increasing in the last years. They are becoming important medical, social and economical problem all over the world. Allergic rhinitis and asthma are one of the most common allergic diseases. Specific allergen immunotherapy (SIT) has additional effects, not shared by pharmacological therapy; it has long-lasting preventive effect, especially the capacity to modify the natural course of the allergic diseases. THE AIM OF THE STUDY: To evaluate the clinical efficacy and costs of specific immunotherapy in patients with allergic diseases. MATERIAL AND METHODS: The study were carried out on the group of 83 allergic patients treated with three-years subcutaneous SIT Clinical efficacy of SIT, costs of SIT and costs of one-year symptomatic treatment before and after SIT were assessed. RESULTS: Three-years subcutaneous allergen-specific immunotherapy decreases allergic symptoms about 80% and reduces costs of symptoms-relieving drug about 70%. Patients with allergic bronchial asthma gain most clinical and economical benefits with SIT while presence of atopic dermatitis is correlated with less effective immunotherapy. CONCLUSION: From public payer's and patient's perspective, SIT essentially reduces costs of symptoms-relieving treatment, especially in patients with allergic bronchial asthma. It can be a premise to consider to increase a level of refund of specific immunotherapy in Poland.

Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis.

UNLABELLED: Eotaxins are the chemokines which are highly selective chemotactic agents for eosinophils. The aim of our study was the evaluation of the gene expression level for eotaxin 1/CCL11, eotaxin 2/CCL24, and eotaxin 3/CCL26, both in skin changes and in uninvolved skin of atopic dermatitis (AD) patients. The study comprised 19 patients with AD and 10 healthy controls. The gene expression level for eotaxins in the skin biopsies was evaluated by the real-time quantitative PCR. The change of the gene expression level, calculated as log10 skin lesions/non-lesional skin, was 0.635 for CCL11, 0.172 for CCL24 and 0.291 for CCL26. The change of the gene expression level, calculated as log10 non-lesional skin of AD patients/healthy control, was 0.394 for CCL11, -0.216 for CCL24, and 0.229 for CCL26, while skin lesions of AD patients/healthy control, was: 0.788, -0.046, and 0.483, respectively. CONCLUSION: The mean gene expression level for CCL11, CCL24, CCL26 was higher in skin changes of AD patients than in uninvolved skin. The higher level of CCL26 in skin changes, indicates its role in their aetiology in AD. The gene expression level for CCL24 in AD patients was lower, both in involved and uninvolved skin vs. the healthy control.

Reaction of the XPA zinc finger with S-nitrosoglutathione.

S-Nitrosoglutathione (GSNO) is an intracellular redox signaling molecule, also implicated in nitrosative stress. GSNO actions include modifications of Cys thiols in proteins. In this study, we focused on a GSNO reaction with a Cys4 zinc finger (ZF) sequence of human protein XPA, crucial to the nucleotide excision repair pathway of DNA repair. By using a corresponding synthetic 37-residue peptide acetyl-DYVICEECGKEFMDSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) and combining the detection of noncovalent and covalent complexes by ESI-MS with zinc release monitored by the zinc-sensitive chromophore 4-(2-pyridylazo)resorcinol (PAR), we demonstrated that the reaction of XPAzf with GSNO yielded S-nitrosylated intermediates, intrapeptide disulfides, and mixed glutathione disulfides. The reaction started with the formation of a complex of GSNO with ZnXPAzf followed by thiol transnitrosylation reactions and the final formation of disulfides. The results obtained suggest that at low levels/transient exposures, GSNO may act as a reversible regulator of Cys4 ZF activity, whereas transnitrosylation by GSNO, occurring at prolonged exposures, may cause deleterious effects to the functions of Cys 4 ZF proteins. In the case of XPA, this may lead to DNA repair inhibition.

Quantitative electrospray ionization mass spectrometry of zinc finger oxidation: the reaction of XPA zinc finger with H(2)O(2).

Oxidation plays an important role in the functioning of zinc fingers (ZFs). Electrospray ionization mass spectrometry (ESI-MS) is a very useful technique to study products of ZF oxidation, but its application has been limited largely to qualitative analysis of reaction products. On the other hand, ESI-MS has been applied successfully on several occasions to determine binding constants in metalloproteins. We used a synthetic 37-residue peptide acetyl-DYVICEECGKEFMDSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf), which corresponds to the Cys4 ZF sequence of human nucleotide excision repair protein XPA, to find out whether ESI-MS might be used quantitatively to study ZF reaction kinetics. For this purpose, we studied oxidation of the Zn(II) complex of XPAzf (ZnXPAzf) by H(2)O(2) using three techniques in parallel: high-performance liquid chromatography (HPLC) of covalent reaction products, 4-(2-pyridylazo)-resorcinol monosodium salt (PAR)-based spectrophotometric zinc release assay, and ESI-MS. Single and double intrapeptide disulfides were detected by ESI-MS to be the sole reaction products. All three techniques yielded independently the same reaction rate, thereby demonstrating that ESI-MS may indeed be used in quantitative kinetic studies of ZF reactions. The comparison of experimental information demonstrated that the formation of the Cys5-Cys8 single disulfide was responsible for zinc release.

Ap4A is not an efficient Zn(II) binding agent. A concerted potentiometric, calorimetric and NMR study.

Diadenosine 5',5''-P(1)P(4) tetraphosphate (Ap(4)A) has been considered as an intracellular partner for Zn(II). We applied potentiometry, ITC and NMR to study protonation equilibria of Ap(4)A and Zn(II) complexation by this dinucleotide. The values of binding constants obtained by these three techniques under various experimental conditions coherently demonstrated that Ap(4)A binds Zn(II) weakly, with an apparent binding constant of ca. 10(4) at neutral pH. Such a low stability of Zn(II) complexes with Ap(4)A excludes a possibility for interactions between these two agents in vivo.

[The effects of amiodaron on the thyroid function]. / Wplyw amiodaronu na czynnosc tarczycy.

The use of several groups of medications may result in thyroid dysfunction including thyrotoxicosis or hypothyroidism of various degree (from subclinical to full-clinical syndrome). The mentioned disturbances may develop either on the basis of normal euthyroid gland or may overlap the previously-existing oceult changes (first of all different forms of autoimmune thyroiditis). Amiodarone is a widely used anti-arrythmic drug with considerable potential to cause thyroid dysfunction because of its 35% iodine content. Besides amiodarone particles are known to inhibit T4 to T3 conversion, they work as inhibitors of nuclear receptors for thyroid hormones, exert cytotoxic effect and induce immune/inflammatory process in thyroid gland. Both thyrotoxicosis (AIT - amiodarone induced thyrotoxicosis) and hypothyroidism (AIH - amiodarone induce hypothyroidism) may develop during amiodarone therapy. AIT appears to occur more frequently in geographical areas with low iodine intake, whereas AIH is more frequent in iodine-sufficient areas. Two forms of AIT are known. Their differentiation is very important for further therapeutical procedures. Because thyrotoxicosis and hypothyroidism symptoms during amiodarone therapy are scanty, there is need for periodic determination of thyroid function. Normal ranges for amiodarone patients differ from those for the rest of population. They are presented in this review. Treatment of AIT is very complicated. Sometimes there is need to use few methods together, especially when amiodarone treatment can not be stopped.

Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis.

Zinc finger motifs participate in protein-nucleic acid and protein-protein interactions in many groups of proteins, including those involved in DNA repair. The Zn(II) ion, bonded tetrahedrally to cysteine thiolates and/or histidine imidazole groups, maintains the three-dimensional structure, crucial for the function of the domain. Zinc fingers can thus be compromised by a substitution of Zn(II) with another metal ion or by a release of Zn(II), due to the oxidation of thiolate donors. The latter may result from an action of redox-active metals or other oxidative agents. Studies in cell cultures and ex vivo demonstrated that soluble compounds of definite carcinogenic metals and metalloids, such as arsenic, cadmium and nickel, and putative carcinogens, including cobalt and lead, inhibit zinc finger containing DNA repair proteins. Further experiments demonstrated that these metals, as well as endogeneous oxidative substances, including hydrogen peroxide, nitrosoglutathione, and reducible selenium compounds damage or distort zinc finger domains. This reactivity can therefore be regarded as a novel molecular mechanism in carcinogenesis.

[Drugs affecting thyroid--part II]. / Leki wplywajace na czynnosc tarczycy - cz. II.

The use of several groups of medications may result in thyroid dysfunction. So far the best known medication is amiodarone. The role of other medications and diagnostic agents in causing thyroid dysfunction is quite often forgotten. We presented medications and diagnostic agents commonly used in medical day-to-day practice. We described other than amiodarone iodinated agents and quoted recently published European guidelines in using iodinate contrast agents. We focused on lithium and psychiatric drugs and mechanism of their toxic impact on thyroid gland. These agents are important as they are applied for years (including children). At the end the impact of cytokines on thyroid gland was discussed, medications ever more widely applied in anti-viral and anti-neoplastic therapy.