Primary immunodeficiencies (PIDs) are inherited disorders in which one or several components of immune system are decreased, missing, or of non-appropriate function. These diseases affect the development, function, or morphology of the immune system. The group of PID comprises more than 200 different disorders and syndromes and the number of newly recognized and revealed deficiencies is still increasing. Their clinical presentation and complications depend on the type of defects and there is a great variability in the relationship between genotypes and phenotypes. A variation of clinical presentation across various age categories is also presented and children could widely differ from adult patients with PID. Respiratory symptoms and complications present a significant cause of morbidity and also mortality among patients suffering from different forms of PIDs and they are observed both in children and adults. They can affect primarily either upper airways (e.g., sinusitis and otitis media) or lower respiratory tract [e.g., pneumonia, bronchitis, bronchiectasis, and interstitial lung diseases (ILDs)]. The complications from lower respiratory tract are usually considered to be more important and also more specific for PIDs and they determinate patients’ prognosis. The spectrum of the causal pathogens usually demonstrates typical pattern characteristic for each PID category. The respiratory signs of PIDs can be divided into infectious (upper and lower respiratory tract infections and complications) and non-infectious (ILDs, bronchial abnormalities – especially bronchiectasis, malignancies, and benign lymphoproliferation). Early diagnosis and appropriate therapy can prevent or at least slow down the development and course of respiratory complications of PIDs.

Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.

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Oncologic diseases are among leading cause of mortality in developed countries. Despite significant progress, the use of standard cytotoxic chemotherapy has reached a therapeutical plateau. Currently, the process of selecting chemotherapy represents a trial and error method neglecting biological individuality of tumor and its bearer. The improvement of treatment results is expected from ex vivo drug sensitivity testing which may allow to choose the most effective drug for individual patient and to exclude agents to which the tumor cells exert resistance. New techniques and rapidly increasing knowledge about the molecular basis of malignant diseases provide important opportunities for the future of chemotherapy. This paper reviews current methods used to test the resistance of tumor cells to a panel of anticancer agents in vitro. In addition, we focused on the in vitro MTT assay which represents one of major technique for testing of tumor cell resistance to anticancer agents.

Bronchial asthma is one of the most common chronic inflammatory diseases of the airways. In the pathogenesis of this disease, the interplay among the genes, intrinsic, and extrinsic factors are crucial. Various combinations of the involved factors determine and modify the final clinical phenotype/endotype of asthma. Oxidative stress results from an imbalance between the production of reactive oxygen species and reactive nitrogen species and the capacity of antioxidant defense mechanisms. It was shown that oxidative damage of biomolecules is strongly involved in the asthmatic inflammation. It is evident that asthma is accompanied by oxidative stress in the airways and in the systemic circulation. The oxidative stress is more pronounced during the acute exacerbation or allergen challenge. On the other hand, the genetic variations in the genes for anti-oxidative and pro-oxidative enzymes are variably associated with various asthmatic subtypes. Whether oxidative stress is the consequence of, or the cause for, chronic changes in asthmatic airways is still being discussed. Contribution of oxidative stress to asthma pathology remains at least partially controversial, since antioxidant interventions have proven rather unsuccessful. According to current knowledge, the relationship between oxidative stress and asthmatic inflammation is bidirectional, and genetic predisposition could modify the balance between these two positions—oxidative stress as a cause for or consequence of asthmatic inflammation.

The effect of oxidative stress on the Ca2+-ATPase activity, lipid peroxidation and protein modification of cardiac sarcoplasmic reticulum (SR) membranes was investigated. Isolated SR vesicles were exposed to FeSO4/EDTA (0.2 micromol Fe2+ per mg of protein) at 37 degrees C for 1 h in the presence or absence of antioxidants. FeSO4/EDTA decreased the maximum velocity of Ca2+-ATPase reaction without a change of affinity for Ca2+ or Hill coefficient. Treatment with radical-generating system led also to conjugated diene formation, loss of sulfhydryl groups, changes in tryptophan and bityrosine fluorescences and to production of lysine conjugates with lipid peroxidation end-products. Lipid antioxidants butylated hydroxytoluene (BHT) and stobadine partially prevented inhibition of Ca2+-ATPase and decrease in tryptophan fluorescence, while the loss of -SH groups and formation of bityrosines or lysine conjugates were completely prevented. Glutathione also partially protected Ca2+-ATPase activity and decreased formation of bityrosine, but it was not able to prevent oxidative modification of tryptophan and lysine. These findings suggest that combination of amino acid modifications, rather than oxidation of amino acids of one kind, is responsible for inhibition of SR Ca2+-ATPase activity.

Aging process is accompanied by various biological dysfunctions including altered calcium homeostasis. Modified calcium handling might be responsible for changed cardiac function and potential development of the pathological state. In the present study we compared the mRNA and protein levels of the intracellular Ca(2+)-handling proteins--inositol 1,4,5-trisphosphate receptor (IP(3)R), ryanodine receptor (RyR), sarcoplasmic reticulum Ca(2+) pump (SERCA2), and also transient receptor potential C (TRPC) channels in cardiac tissues of 5-, 15-, and 26-month-old rats. Aging was accompanied by significant increase in the mRNA levels of IP(3)R and TRPC channels in both ventricles and atria, but mRNA level of the type 2 RyR was unchanged. Protein content of the IP(3)R1 correlated with mRNA levels, in the left ventricle of 15- and 26-month-old rats the value was approximately 1.8 and 2.8-times higher compared to 5-month-old rats. No significant differences were observed in mRNA and protein levels of the SERCA2 among 5-month-old and aged rats. However, Ca(2+)-ATPase activity significantly decreased with age, activities in 5-, 15-, and 26-month-old rats were 421.2 +/- 13.7, 335.5 +/- 18.1 and 304.6 +/- 14.8 nmol P(i) min(-1) mg(-1). These results suggest that altered transporting activity and/or gene expression of Ca(2+)-handling proteins of intracellular Ca(2+) stores might affect cardiac function during aging.

BackgroundAsthma is a heterogeneous disease with variable symptoms especially in children. Exhaled nitric oxide (FeNO) has proved to be a marker of inflammation in the airways and has become a substantial part of clinical management of asthmatic children due to its potential to predict possible exacerbation and adjust the dose of inhalant corticosteroids.ObjectivesWe analyzed potential factors that contribute to the variability of nitric oxide in various clinical and laboratory conditions.Materials and methodsStudy population consisted of 222 asthmatic children and 27 healthy control subjects. All children underwent a panel of tests: fractioned exhaled nitric oxide, exhaled carbon monoxide, asthma control test scoring, blood sampling, skin prick tests, and basic spirometry.ResultsFeNO and other investigated parameters widely changed according to clinical or laboratory characteristics of the tested children. Asthmatics showed increased levels of FeNO, exhaled carbon monoxide, total serum IgE, and higher eosinophilia. Boys had higher FeNO levels than girls. We found a significant positive correlation between FeNO levels and the percentage of blood eosinophils, %predicted of forced vital capacity, total serum IgE levels, and increasing age.ConclusionsVarious phenotypes of children's asthma are characterized by specific pattern of the results of clinical and laboratory tests. FeNO correlates with total serum IgE, blood eosinophilia, age, and some spirometric parameters with different strength. Therefore, the coexistence of atopy, concomitant allergic rhinitis/rhinoconjunctivitis, and some other parameters should be considered in critical evaluation of FeNO in the management of asthmatic children.