Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide.

PURPOSE: Eosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts. MATERIAL AND METHODS: NP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10(-7)M to 10(-4)M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method. RESULTS: The highest calcitriol concentration (10(-4)M) as well as tacalcitol at 10(-5)M and 10(-4)M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively). CONCLUSION: Active VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.

Vitamin D derivatives: calcitriol and tacalcitol inhibits interleukin-6 and interleukin-8 expression in human nasal polyp fibroblast cultures.

PURPOSE: Biologically active vitamin D3 (VD) derivatives possess modulatory activities on immunological and inflammatory responses which can be reflected by altered levels of pro-inflammatory chemokines. Nasal polyposis (NP), defined as a chronic inflammatory process of upper respiratory system, could be influenced by VD derivatives. The purpose of this study was to investigate the influence of 1alpha,25-dihydroxyvitamin D3 (calcitriol) and 1alpha,24(R)-dihydroxyvitamin D3 (tacalcitol) on the secretion of IL-6 and IL-8 by fibroblasts derived from NP. MATERIAL AND METHODS: The study involved 12 fibroblast cultures derived from NP samples obtained from surgically treated patients. Measurements were performed on the polyp cells after the 6-9 passages. Culture stimulation involved treatment with tacalcitol and calcitriol at a defined strength (from 10(-7)M to 10(-4)M). IL-6 and IL-8 concentrations were estimated with ELISA. RESULTS: Treatment with calcitriol or tacalcitol inhibits the synthesis of both IL-6 and IL-8 compared to the control group. The dose dependence of this effect has been confirmed. VD derivatives influence was marked at higher concentrations. Significant interleukin decrease was observed at 10(-5) and 10(-4) for calcitriol and 10-4 in the case of tacalcitol. CONCLUSIONS: The present study demonstrates that calcitriol and tacalcitol are capable of affecting pro-inflammatory cytokine (IL-6 and IL-8) levels in NP cultures. Our data imply a potential therapeutical application of topical VD derivates in NP and warrant further investigation.

Transcriptional activity of genes-encoding kinin B1 and B2 receptors and kinin-dependent genes in nasal polyps.

PURPOSE: The pro-inflammatory effects of kinins are mediated by two bradykinin receptors: BR1 and BR2. The aim of this study was to evaluate the expression profile of kinin receptor genes by an estimation of mRNA levels in human nasal polyps (NP) and normal mucosa (NM). MATERIAL AND METHODS: BR1 and BR2-dependent genes differentially transcribed in NP were investigated using oligonucleotide microarray technology. The mRNA copy number of BR1, BR2 and TIMP1 genes was assessed by QRT-PCR. Thirty six eosinophilic (ENP), 17 neutrophilic nasal polyps (NNP) and 28 NM samples were included into the study. RESULTS: Among 92 genes encoding proteins involved in signal transduction via B1 and B2 kinin receptors TIMP1 was found to be 2,63-fold higher in the NP than in NM. Increased TIMP1 gene expression was proved by QRT-PCR (p=0,003). Moreover two genes: FOS and PTGS1 presented higher (3,82- and 4,27-fold, respectively) expression in NM compared to NP tissues. In QRT-PCR analysis insignificantly higher expression of gene encoding BR1 in ENP [2564 mRNA copies/microg RNA (22-32863)] compared with NM [1426 copies mRNA (15-27995)] was found. mRNA expression for the BR2 in ENP [9872 copies mRNA (19-244832)] was insignificantly higher than in NM [5753 copies (46-199658)]. BR2 mRNA was the predominant transcript in most NP and NM samples followed by BR1 mRNA (p<0,01). There was a positive correlation between the expression of BR1 and BR2 in the ENP (r=0,91; p<0,01) and NNP (r=0,6; p<0,01). CONCLUSIONS: We did not document any changes in the expression profile of kinin receptors in the analyzed groups, which may suggest that kinin receptors do not make an important contribution in the etiology of NP.

Quantification of the mRNA encoding Tumor Necrosis Factor alpha (TNFalpha) and its receptors in human nasal polyps.

PURPOSE: The object of the study was to assess the expression of the genes encoding TNFalpha and its receptors (TNF-R1 and TNF-R2) in patients with nasal polyps (NP). MATERIAL AND METHODS: The number of the mRNA copies was assessed by QRT-PCR in RNA extracts from 16 eosinophilic (ENP) and 5 neutrophilic nasal polyps (NNP), and 9 normal mucosa (NM) samples. The expression of corresponding proteins was demonstrated using immunohistochemistry. RESULTS: The mean level of mRNA copies for TNFalpha in ENP (82229c/microg) was not significantly higher when compared with controls (74869c/microg). NNP demonstrated significantly lower mean TNFalpha gene expression (7021c/microg) than the controls (p<0.05). A statistically higher mRNA TNFalpha copy number in ENP than in NNP was also revealed (p<0.01). A noticeably lower mRNA expression of TNF-R1 in ENP and NNP was seen as compared to the control group (10198c/microg vs. 30749c/microg, p<0.05 and 3440c/microg vs. 30749c/microg; p<0.05 respectively). In ENP the mean TNF-R2 mRNA copy number was markedly higher than in NNP (185c/microg vs. 7.6c/microg, p<0.05). TNF-R2 mRNA level did not differ significantly between ENP and the control group (185c/microg vs. 469c/microg). TNF-R1 expression was significantly higher than TNF-R2 at the mRNA (p<0.01) and protein (p<0.05) level both in ENP and NNP. No significant correlations in proteins expression were detected between ENP and NNP. CONCLUSIONS: TNF-R1 has been identified to be a prevalent form of the TNFalpha receptor in nasal polyps which may reflect the apparent dominance of this form in TNFalpha signalling. The findings raise the possibility that the eosinophils from NP may influence biological responses through TNFalpha-dependent mechanisms. The differences between ENP and NNP relating to TNFalpha and the expression of its receptors may reflect the distinct character of those diseases.

Content of trace elements in serum of patients with carcinoma of the larynx.

An examination of the content of arsenic, nickel, copper, selenium, zinc, and iron in the serum of 78 patients with carcinoma of the larynx was carried out. The patients were divided into 4 groups: I - patients before treatment, II - patients after surgical treatment, III - patients after radiotherapy, IV - patients after combined treatment (surgery treatment + radiotherapy). The control group was formed of 17 patients operated for deviation of the nasal septum. Higher concentrations of arsenic, nickel and copper were found in the serum of the patients with carcinoma of the larynx before treatment (group I) as compared with the control group, whereas the concentrations of selenium, zinc and iron were lower. In the groups of patients after treatment, the highest concentrations of iron and zinc were found after surgical treatment. The level of selenium in all groups of patients was considerably lower than in the control group.

[The content of some trace elements in tissue of laryngeal squamous cell carcinoma]. / Zawartosc niektórych pierwiastków sladowych w tkance raka plaskonablonkowego krtani.

The examination of the content of arsenic, nickel, copper, selenium, zinc, iron, cadmium, lead, cobalt, antimony and tin in the tissue of laryngeal squamous cell carcinoma was carried out. Material was taken from tumour of the larynx of 22 patients during laryngectomy. The control group was made up by healthy tissue of the larynx taken from 14 patients during diagnostic examinations. Trace elements were determined by means of BAIRD plasma spectrometer. Higher values of the concentration of arsenic, nickel, copper, cadmium, lead and cobalt were found in the tissue with carcinoma of the larynx as compared with the control group. The concentration of selenium, zinc, and iron in the carcinoma tissue was lower than in the healthy tissue. The concentration of antimony and tin was similar to that of the control group.

[Auditory evoked potentials from brain stem determined in acoustic nerve neurinomas]. / Badanie wywolanych potencjalów sluchowych z pnia mózgu (PSPW) w przypadkach nerwiaków nerwu sluchowego.

An analysis of the studies of Brain Stem Electric Response Audiometry of patients operated on Bachaumont Clinic or in Cochin hospital in Paris, because of acoustic neurinoma, was carried out. The studies comprised 88 patients divided into groups according to the size of tumour. A group of small intrameatal tumours, a group of up to 2 cm tumours, a group of between 2 and 3 cm tumours and a group of above 3 cm tumours. A control group of examined patients consisted of 20 persons with one-side acoustic impairment or two-side impairment but predominant on one side and patients with one-side tinnitus or two-side tinnitus but predominant on one side. Examinations of these patients made with CT and NMR did not show presence of acoustic neurinoma. BERA's tests did not show a response in case of 22 patients with acoustic neurinoma. In 71% of cases BERA's tests showed an extrahelix type, for which in 50% of cases a prolonged latency on the side of the tumour was found. In 4% of cases Brain Stem Electric Response Audiometry gave results within normal range both with respect to morphology and latency time of each wave. A slight correlation between the size of tumour and type of BERA change was found.

[Progress in research for new drugs against the herpes virus]. / Postepy w badaniach nad nowymi lekami przeciw wirusom herpes.

Significant advances have been made in the development of effective antiherpes-virus chemotherapy in the last decades. Acyclovir was approved for the treatment of HSV infections over 15 years ago and it remains an important and reliable antiviral agent. In this review the most promising new antiviral drugs are described. It will focus on the drugs that have just entered the therapy, or will do so within a short period of time. Some of the them are still under clinical investigation. Antiviral activity, results of clinical trials and adverse effects will be presented.

[Influence of vapours of paint and toxic dusts on mucous membranes of the upper airways in paint and varnish factory workers]. / Wplyw par rozpuszczalników i pylów toksycznych na blony sluzowe górnych dróg oddechowych pracowników fabryki farb i lakierów.

Macroscopic, cytologic and bacteriologic conditions of mucous membranes of the upper airways in workers (n = 146) of the Polifarb Factory, Wroclaw, exposed to dusts and solvent vapours used in the paint and varnish production was estimated. In 89% of the workers, pathologic changes in throat mucous membranes were observed. Three types of macroscopic changes were distinguished. In workers with the shortest period of employment, laryngeal oedema congestion alteration was diagnosed, and atrophic changes with medium intensity were observed in workers employed for a long period. It was found that cytologic changes in the nose mucous membrane depended on the duration of exposure. Inflammation cytograms appeared during the first period of exposure to the substances discussed. The longer period of exposure, the more clear features of metaplasia squamous epithelium. The composition of the nose and throat bacterial flora changed according to the length of employment. An increased growth of G(-) genera Enterobacter, Klebsiella, Proteus, Escherichia and Candida fungi was found in workers with long period of employment.