[The application of N-acetylcysteine in optimization of specific pharmacological therapies]. / Zastosowanie N-acetylocysteiny do optymalizacji specyficznych terapii farmakologicznych.

Based on the analysis of data from clinical trials it could be postulated that N-acetylcysteine has a positive impact on the treatment of various diseases. However, less is known about specific molecular and physiological mechanisms underlying the reported therapeutic effects. N-acetylcysteine (NAC, N-acetyl-L-cysteine) is an amino acid derivative containing a thiol group. It is a precursor of L-cysteine and glutathione. NAC is well absorbed and safe for the body at doses up to 300 mg per kg of body weight. Side effects are relatively rare. NAC is used as an mucolytic agent in adjunctive therapy of respiratory diseases causing the retention of secretions, as well as an antidote in the treatment of paracetamol poisoning. Moreover, NAC protects against the toxic effects of reactive oxygen species and their active metabolites. NAC is involved in free radical scavenging processes via several independent mechanisms, including a direct reduction of free radicals, providing substrates for oxidation-reduction reactions and activation of antioxidant enzymes. In the blood, NAC decreases the level of low density lipoprotein peroxidation. In various tissues, NAC may increase the levels of glutathione and cysteine and stimulate the superoxide dismutase action. NAC is used as a supplement in the treatment of various diseases associated with impaired exterior and intracellular oxidative balance. NAC increases the concentrations of amino acids and their derivatives, including cysteine, cystine, and glutathione. It also stabilizes the antioxidant status of the cells and the intercellular spaces. NAC changes the levels of transcription factors, modifying the transcription of selected genes and acting on the protein translation. It works on the activation of several enzymes in the cells and outside the cells. Based on the analysis of data from clinical trials it can be concluded, that an administration of NAC may be beneficial for these groups of patients, in whom the reversible accumulation and the negative action of free radicals was observed.

Time-dependent changes of plasma concentrations of angiopoietins, vascular endothelial growth factor, and soluble forms of their receptors in nonsmall cell lung cancer patients following surgical resection.

Even when patients with nonsmall cell lung cancer undergo surgical resection at an early stage, recurrent disease often impairs the clinical outcome. There are numerous causes potentially responsible for a relapse of the disease, one of them being extensive angiogenesis. The balance of at least two systems, VEGF VEGFR and Ang Tie, regulates vessel formation. The aim of this study was to determine the impact of surgery on the plasma levels of the main angiogenic factors during the first month after surgery in nonsmall cell lung cancer patients. The study group consisted of 37 patients with stage I nonsmall cell lung cancer. Plasma concentrations of Ang1, Ang2, sTie2, VEGF, and sVEGF R1 were evaluated by ELISA three times: before surgical resection and on postoperative days 7 and 30. The median of Ang2 and VEGF concentrations increased on postoperative day 7 and decreased on day 30. On the other hand, the concentration of sTie2 decreased on the 7th day after resection and did not change statistically later on. The concentrations of Ang1 and sVEGF R1 did not change after the surgery. Lung cancer resection results in proangiogenic plasma protein changes that may stimulate tumor recurrences and metastases after early resection.

Circulating endothelial cells in coronary artery disease.

BACKGROUND: endothelial damage and dysfunction play a crucial role in the pathophysiology of coronary artery disease (CAD). The quantification of circulating endothelial cells (CEC) in the peripheral blood is a novel method for assessing endothelial damage. AIM: to evaluate the possible diagnostic use of single quantification of CEC in peripheral blood by flow cytometry in patients with CAD. METHODS: we examined 48 patients with CAD, including 23 patients with acute myocardial infarction (AMI) and 25 patients with stable angina (SA). The control group consisted of 20 healthy subjects without symptoms of CAD. The CEC count was evaluated by flow cytometry using antibodies against CD31, CD146, and CD45. Plasma biochemical markers of endothelial damage (von Willebrand Factor [vWF], thrombomodulin [TM]) were measured by ELISA. Serum concentrations of troponin I (TnI) and lipid parameters were also included in the statistical analysis. RESULTS: A significant increase in the CEC count was found in patients with AMI compared to the control group (p < 0.05) and SA patients (p < 0.05). However, no difference was found in the CEC count between patients with SA and the control group. Increased vWF activity was found in both groups of CAD patients compared to the control group (AMI: p < 0.001, SA: p , 0.01), and vWF activity was significantly higher in AMI patients compared to SA patients (p < 0.001). Thrombomodulin concentration did not differ significantly between any patient groups and the control group. The CEC count correlated positively with vWF activity (r = 0.3852, p < 0.05) and the atherogenic index TC/HDL-C (r = 0.3844, p < 0.05) in all patients with CAD (AMI + SA). The sensitivity of CEC count for the diagnosis of an acute coronary syndrome was lower than that of TnI level on admission (39% vs 69%). CONCLUSIONS: we confirmed that CEC count in peripheral blood can be determined by flow cytometry in CAD patients with both AMI and SA. The CEC count in AMI was increased in comparison to healthy subjects and SA patients in one third of all cases. To determine whether CEC count could be used to improve the diagnosis of an acute coronary syndrome in patients with CAD, additional studies in larger patient groups would be required.

[The estimation of serum concentration of vascular endothelial growth factor in patients with non-small cell lung cancer]. / Ocena stezenia naczyniowo-sródblonkowego czynnika wzrostu w surowicy u chorych na niedrobnokomórkowego raka pluca.

UNLABELLED: Vascular endothelial growth factor (VEGF) is main angiogenic factor, which stimulates endothelial cells migration and proliferation. The extensive angiogenesis plays important role in tumor growth and metastasis. AIM OF THE STUDY: Analysis of serum concentrations of vascular endothelial growth factor in patients with non-small cell lung cancer depending on clinicopathologic findings. MATERIAL AND METHODS: The study group consisted of 50 patients with non-small cell lung cancer (16 females and 34 males) ranging in age from 47 - 80 years (mean age 63 +/- 8.2). Serum VEGF concentration was evaluated by ELISA. RESULTS: VEGF concentrations in serum did not differ significantly between groups of patients with different T-, N- and M-factor. Patients with inoperable tumor (IIIB and IV) had significantly higher serum VEGF concentrations compared with resected tumor (I-IlIA) and locally advanced cancer (IIIA). CONCLUSIONS: Serum VEGF may be a marker of tumor progression in non-small cell lung cancer.

[The serum concentration of metalloproteinase 9 and 2 in non-small cell lung cancer patients]. / Stezenie metaloproteinazy 9 i 2 w surowicy chorych na niedrobnokomórkowego raka pluca.

UNLABELLED: Matrix metalloproteinases are responsible for the proteolytic degradation of the basement membrane and extracellular matrix. Elevated expression levels of MMP-9 and MMP-2 have been associated with tumor invasion and metastasis. THE AIM OF THIS STUDY: To determine serum concentrations of metalloproteinases 9 and 2 in non-small cell lung cancer patients depending on tumor stage. MATERIAL AND METHODS: The study group consisted of 50 patients with non-small cell lung cancer (16 females and 34 males) ranging in age from 47 - 80 years (mean age 63 +/- 8.2). MMP-9 and MMP-2 concentrations in serum were evaluated by ELISA. RESULTS: MMP-9 and MMP-2 concentrations in serum did not differ significantly between group with different T- and N-factor. Serum level of MMP-9 was significantly higher in patients with metastases than those without them. Patients with inoperable tumor (IIIB - IV) had significantly higher serum MMP-9 concentrations compared with resected tumor (I - IlIA). CONCLUSIONS: Serum MMP-9 may be a marker of metastasis in non-small cell lung cancer.

[Cellular tumor markers in thyroid cancer]. / Komórkowe markery nowotworowe w raku tarczycy.

Thyroid cancer is the most common endocrine malignancy. Most patients with thyroid cancer have a great chance for successful treating. There is, however, a group of patients with poor prognosis. The present researches of thyroid tumor markers have related to permanent diagnostic progress of circulating markers analysis (thyroglobulin, thyroid peroxidase, calcitonin and carcinoembryonic antigen), cellular markers determination and interpretation of results, also. A number of molecular markers have been studied. Diagnostic value of some of them, e.g. TSHR, RET Ras, is well known. Others have investigated continually. Overexpression of BRAF, Met, and p53 has been correlated with aggressiveness of the cancer. Markers said to be of prognostic value in thyroid cancer are CD82, c- myc and Plk-1. The combination of markers: galectin-3, fibronectin and HBME-1 have proven to be sensitive for differentiated thyroid cancer. Further studies on new cellular thyroid markers are essential. The current review presents data concerning the well known cellular markers in thyroid cancer.

[Iron status with particular consideration of soluble transferrin receptors in children and youth with gastritis, with or without Helicobacter pylori infection]. / Stan gospodarki zielazem ze szczególnym uwzglidnieniem I osoczowych receptorów transferyny u dzieci i mlodziezy z przewleklym zapaleniem blony sluzowej ioladka ze wspólistniejacym zaka eniem Helicobacter pylori lub bez zakaienia.

UNLABELLED: Role of Helicobacter pylori infection in chronic gastritis and gastric and/or duodenal ulcers is well known. Simultaneously there are some articles in literature considering H. pylori as a cause of extra-gastrointestinal illnesses such as atopic dermatitis, chronic urticaria or acne rosacea, hypotrophy, Schoenlein-Henoch disease, atherosclerosis or hypochromic anaemia. The aim of the study. was to asses iron status in aspect of plasmatic transferrin receptors concentration among children and youth with chronic gastritis with or without Helicobacter pylori infection. MATERIALS AND METHODS: Forty one patients were included as a study group. Range of age was 9-18 years. All patients were diagnosed due to chronic abdominal pains. There were 13 males and 28 females. Blood was collected from every patient for blood cell count, iron, transferrin and transferrin receptors concentration (sTfR) assessment before endoscopy of upper gastrointestinal tract. RESULTS: Concentration of sTfR was higher than age norm among 29 (71%) of patients. Among patients with higher level of sTfR 20 (69%) had normal haemoglobin concentration and in this group 10 patients had H. pylori infection. During analysis of 12 patients with nornal level of sTfR normal haemoglobin concentration was found and among five of them H. pylori infection was stated. Among 21 patients without H. pylori infection 14 had normal level of sTfR and 7 had higher level of sTfR which means that 33% had hidden iron deficiency (involuntary of normal Hb concentrations). Among 15 of 20 patients with H. pylori infection level of sTfR was higher which means that 75% patients with infection had hidden iron deficiency (involuntary of normal Hb concentrations). CONCLUSION: Level of plasmatic transferrin receptors can be good and sensitive indicator of iron deficiency and can be helpful in differential diagnosis of hypochromic anaemia and anaemia caused by chronic illness including chronic gastritis with Helicobacter pylori infection.

[BRAF gene mutation in thyroid cancer]. / Mutacja genu BRAF w raku tarczycy.

Mutations of genes coding effectors of signaling pathway RET/PTC-RAS-RAF-MEK-ERK, involved in cell growth and proliferation, are important in papillary thyroid cancer development. To earlier discovered mutations of RAS and RET/PTC genes, BRAF gene mutation has been recently added. Mutation of BRAF gene appears in various types of carcinomas, but most frequently in malignant melanomas (66%) and papillary thyroid cancer (average 44%). The BRAF gene protein product belongs to the serine-threonine kinase family and to the RAF proteins subfamily, among which it is the strongest activator of MAP kinases cascade. The most frequently mutation of BRAF gene is thymine to adenine transversion at nucleotide position 1796 (T1796A). This point mutation causes valine to glutamic acid substitution at residue 599 (V599E), that results in constitutive and oncogenic activation of BRAF kinase. The relation between mutations of BRAF, RAS and RET/PTC genes has not been found, although they together exist in two thirds of papillary thyroid cancers. BRAF(TI796A) oncogene appears in papillary thyroid cancer, whereas it has not been found in follicular thyroid cancer and benign thyroid adenomas. For this reason mutated BRAF gene could be specific molecular marker, with relatively high sensitivity in diagnostics of papillary thyroid cancer. In addition, BRAF gene has been demonstrated as a novel prognostic biomarker, which correlates with unfavorable clinicopathological factors, such as extrathyroidal invasion and distant metastasis.

Clinical and experimental aspects of cutaneous neurogenic inflammation.

The aim of this paper is to present the state of knowledge on cutaneous neurogenic inflammation. Peripheral effector functions served by afferent sensory neurons underlie the so-called neurogenic inflammation. The mechanism of cutaneous neurogenic inflammation is connected with the release of neuropeptides from the sensory endings. They also exert a number of functions within the immune system. The activity of neuropeptides in the inflammation of the skin can be observed in the form of erythema, edema, hyperthermia and pruritus. Beside these peptides and their receptors, inflammatory skin response, is regulated by tryptase and proteinase-activated receptor 2 (PAR-2). Capsaicin decreases effects of inflammation-induced sensory neuropeptides, which was used in the treatment of diseases caused by inflammation. The activity of transient receptor potential vanilloid receptor 1 (TRP-V1) is associated with the neurogenic inflammation. In inflammatory processes, the neuro-immuno-cutaneous system undergoes activation, which is responsible for triggering and maintaining the inflammatory conditions, both in the healthy skin as well as in the pathological conditions, like psoriasis. Skin exposure to UV radiation influences the neuro-immuno-cutaneous system and causes the release of neuropeptides, thereby eliciting inflammatory response in photodermatosis. In conclusion, understanding the mechanisms and the factors controlling neurotransmitters and their receptors will lead to the identification of novel therapeutic targets for the treatment of cutaneous diseases e.g. pruritus, psoriasis, alopecia areata.

Model study of toluene diisocyanate effect on transepithelial ion transport.

BACKGROUND: Toluene diisocyanate (TDI), a low molecular weight compound, is commonly known as a factor causing asthma in chemical industry workers. The present study investigated a possible effect of TDI on ion transport using electrophysiological methods aimed at assessment of ion currents occurring in epithelial tissues. MATERIAL/METHODS: The experiments were carried out on 119 fragments of isolated frog skin, sampled from 59 specimens of hybrid frog Rana esculenta L. The procedures employed involved transepithelial electrical potential (PD in mV) measurement with an Ussing apparatus, modified to enable mechanical stimulation of organs and defined pharmacological actions. Incubation was carried out using Ringer solution and Ringer solution with amiloride and bumetanide. Direct actions of toluene diisocyanate (TDI) were assessed at the time of administering this substance to the Ussing chamber with a peristaltic pump. RESULTS: Based on the model of frog skin tested with Ussing apparatus, administration of TDI to the fluid stimulating preparations incubated with Ringer solution (RH) and with amiloride (AMI) was demonstrated to cause a hyperpolarization increase after mechanical stimulation. TDI action on isolated frog skin inflicted a change in response to mechanical stimulation, leading to a depolarization. The reaction magnitude of frog skin incubated with bumetanide (BUME) did not change due to TDI. CONCLUSIONS: TDI influences processes of sodium ion transport in the isolated frog skin model, depending on mechanical stimulation. This indicates that TDI effect on ion transport in epithelial cells depends on C fibres and tachykinins released from their endings.