Serum fetuin-A level is independent of Helicobacter pylori postinfection status in systemic lupus erythematosus.

Helicobacter pylori is a common pathogen causing gastric inflammation and malignancy. Fetuin-A is a multifunctional protein that is involved in the regulation of calcification, insulin resistance and inflammation. Reports on serum levels of fetuin-A in acute H. pylori infection are contradictory. We intended to see whether H. pylori post-infection status has a long-term effect on serum fetuin-A levels in a well-characterized series of systemic lupus erythematosus cases. In this cross-sectional study 117 patients with systemic lupus erythematosus were enrolled. Helicobacter infection status and serum fetuin-A concentration were determined by ELISA and radial immunodiffusion, respectively. H. pylori positive patients had higher serum fetuin-A concentration than negative ones: 517 (456-603) vs. 476 (408-544) mg L-1, median (25-75% percentiles), P = 0.020. No other parameters differed between these groups. During univariate regression analysis fetuin-A levels were associated with Erythrocyte sedimentation rate (ESR), White blood cell count (WBC), C-reactive protein (CRP), serum total protein, albumin, and the SLEDAI index at the time of diagnosis but only serum albumin remained a significant determinant in multivariate regression study.

Cisplatin treatment induced interleukin 6 and 8 production alters lung adenocarcinoma cell migration in an oncogenic mutation dependent manner.

BACKGROUND: The predominant metastatic site of lung cancer (LC) is the brain. Although outdated, conventional cisplatin treatment is still the main therapeutic approach for patients with advanced non-small cell lung cancer (NSCLC), since targeted therapy that offers better tumor control is not always possible. In the present study brain metastasis associated cytokine expression was investigated in primary NSCLC adenocarcinoma (AC) tissues with known oncogenic mutations in the presence or absence of platina based and tyrosine kinase inhibitor (TKI) drugs. METHODS: Primary lung tumor samples were isolated, DNA was sequenced and then the samples were grouped based on mutation. Experiments were also performed using KRAS mutant A549 and EGFR mutant PC-9 cells. Drug response was analyzed in three dimensional (3D) tissue cultures. We assessed drug response and IL-6 and IL-8 cytokine expression in relation to cellular invasion using ATP dependent cell viability, qRT-PCR analysis, cytokine bead array, and migration assay. RESULTS: In 3D co-cultures, primary NSCLC derived cells harboring EGFR mutation responded better to erlotinib treatment than KRAS mutant or KRAS/EGFR wild type (WT) cancer cells. In contrast, under the same culture conditions KRAS/EGFR WT or KRAS mutant cancer cells are more sensitive to cisplatin than EGFR mutant cells. Drug response and pro-inflammatory cytokine production varied depending on the driver mutations. Cisplatin but not erlotinib increased both IL-6 and IL-8 secretion and only IL-6 increased cellular migration and proliferation. CONCLUSION: In vitro assays are available to determine the response to planned therapeutic approach of lung cancer subtypes. The sequence of administration of therapeutic drugs determines cytokine production and therefore therapeutic response.

Real-Time Locating System in Production Management.

Real-time monitoring and optimization of production and logistics processes significantly improve the efficiency of production systems. Advanced production management solutions require real-time information about the status of products, production, and resources. As real-time locating systems (also referred to as indoor positioning systems) can enrich the available information, these systems started to gain attention in industrial environments in recent years. This paper provides a review of the possible technologies and applications related to production control and logistics, quality management, safety, and efficiency monitoring. This work also provides a workflow to clarify the steps of a typical real-time locating system project, including the cleaning, pre-processing, and analysis of the data to provide a guideline and reference for research and development of indoor positioning-based manufacturing solutions.

Biotransformation of trichothecenes alleviates the negative effects of T-2 toxin in pigs.

Between 49 and 70 days of age, three groups of growing pigs (n = 10 each) were fed diets containing 0, 0.3 and 0.5 mg/kg T-2 toxin, respectively, for 21 days. The feed of another two groups of pigs (n = 10 each) contained 0.3 or 0.5 mg/kg T-2 toxin, respectively, plus a feed additive developed for splitting up the molecular structure of Fusarium toxins, in particular trichothecenes, by deepoxidation of the molecule, at 2 kg/tonne concentration. One group (n = 10) served as positive control; their feed was free from T-2 toxin but contained the feed additive at the above concentration. Toxin concentrations at these low dietary levels impaired the feed intake and growth rate of pigs. The feed additive alleviated the negative effects and justified its potential for prevention. Data of the present study indicated a 0.2 mg/kg feed no observed effect level (NOEL) of T-2 toxin in growing pig feeds.

[Ethiopathogenesis of spontaneous primary pneumothorax. Marijuana: cause or a blame?]. / A spontán primer légmell aetiopathogenesiséhez. Marihuána: ok vagy bunbak?

OBJECTIVE: There are contradictory data on chronic lung injury caused by marijuana, which is partially due to insufficient basic research. Anecdotic reports draw attention to an increased rate of primary spontaneous pneumothorax (PSP) among young marijuana smokers, suggesting a causative link. METHODS: A retrospective analysis of 20 patients treated for PSP in our department in the last two years was performed. Demographics, treatment modality and outcome data were analysed. Chi-square, Mann-Whitney and Fisher tests were applied for statistical evaluation. Gender distribution: 16 male, 4 female, age 23.95 ± 4,57 years: min: 18, max: 32. 13/20 patients admitted to be regular cannabis users (CU), among them 11 male, 2 female, age 24.54 ± 4.77 years. Altogether 7/20 patients had a history of previous pneumo-thorax, with a higher recurrence rate among CU (odds ratio 1.56). RESULTS: In the non-cannabis user group (NCU) 3/7 patients were managed with thoracic drainage alone. 4/7 NCH patients needed major surgery, VATS was performed on all 4 patients. 4/13 CU patients were managed with thoracic drainage, 9/13 patients needed thoracotomy (8 VATS, 1 open thoracotomy). We found a shorter drainage time among NCU patients (4.00 ± 1.00 days NCU vs 4.5 ± 1.73 days CU, p = 0.651). Operative treatment was needed more frequently among cannabis users (69.23% vs NCU 57.14%, p = 0.651) due to impaired lung expansion. Recurrence was detected in 2 patients after drainage, 1 CU, 1 NCU patients, respectively, both of them were managed with VATS. On histological examination there were no major differences between the two groups, 11/13 of operative cases had pulmonary emphysaema . Based on county demographical and clinical data, there's a higher risk for PSP among cannabis users (odds ratio 3.86). CONCLUSIONS: Despite the small sample size, there seems to be a connection between marijuana use and PSP prevalence. It's unclear if marijuana directly contributes to the development of pneumothorax, or just aggravates a fundamentally fragile lung parenchyma condition. In this group of young patients a more aggressive surgical approach is recommended, considering underlying parenchymal impairment and higher recurrence rate.

Interleukin-23 receptor gene variants in Hungarian systemic lupus erythematosus patients.

OBJECTIVE: We investigated the association between systemic lupus erythematosus (SLE) and polymorphisms of interleukin-23 receptor (IL23R) gene, which was recently found to be associated with autoimmune diseases, including Crohn's disease, rheumatoid arthritis, psoriasis and ankylosing spondylitis. SUBJECTS: We analysed 383 SLE patients and 253 controls for rs11805303, rs10889677, rs1004819, rs2201841, rs11209032, 11209026, rs10489629, rs7517847 and rs7530511 variants. METHODS: The analysis was carried out using PCR-RFLP methods. Logistic regression analysis was used to compare the genotype distributions of the polymorphisms and haplotypes between the SLE patients and healthy controls. RESULTS: We observed no significant difference of the examined variants between the patient and control groups. CONCLUSIONS: Our results suggest that neither single nucleotide variants nor haplotypes of IL23R indicate susceptibility to developing SLE in the Hungarian population.

The effect of long-term danazol prophylaxis on liver function in hereditary angioedema-a longitudinal study.

BACKGROUND: Danazol is a drug most widely used for the prophylaxis of hereditary angioedema resulting from the deficiency of the C1-inhibitor. Potential hepatotoxic or liver tumor-inducing side effects of long-term danazol prophylaxis have been investigated during the follow-up of hereditary angioedema patients. METHODS: Characteristic parameters of liver function (including bilirubin, GOT, GPT, gammaGT, total protein, ALP, LDH), as well as findings of viral serology screens and abdominal ultrasonography-determined during years 0 and 5 of follow-up of patient groups taking/not taking danazol-have been reviewed and analyzed comparatively. RESULTS: From a population of 126 hereditary angioedema patients, 46 subjects taking danazol and another 46 not taking danazol fulfilled the inclusion criteria. Longitudinal follow-up did not reveal any clinically relevant difference between the liver function parameters determined in years 0 and 5 in the two groups. Abdominal ultrasound did not detect neoplastic or other potentially treatment-related alterations of the liver parenchyma. There were no discontinuations of treatment during the study. CONCLUSIONS: Our results clearly suggest that, administered at the lowest effective dose, danazol does not induce liver injury in hereditary angioedema patients.

Feasibility study of in vitro drug sensitivity assay of advanced non-small cell lung adenocarcinomas.

Background Despite improved screening techniques, diagnosis of lung cancer is often late and its prognosis is poor. In the present study, in vitro chemosensitivity of solid tumours and pleural effusions of lung adenocarcinomas were analysed and compared with clinical drug response.Methods Tumour cells were isolated from resected solid tumours or pleural effusions, and cryopreserved. Three-dimensional (3D) tissue aggregate cultures were set up when the oncoteam reached therapy decision for individual patients. The aggregates were then treated with the selected drug or drug combination and in vitro chemosensitivity was tested individually measuring ATP levels. The clinical response to therapy was assessed by standard clinical evaluation over an 18 months period.Results Based on the data, the in vitro chemosensitivity test results correlate well with clinical treatment response.Conclusions Such tests if implemented into the clinical decision making process might allow the selection of an even more individualised chemotherapy protocol which could lead to better therapy response.

The effect of the Progesterone-Induced Blocking Factor (PIBF) on E-cadherin expression, cell motility and invasion of primary tumour cell lines.

In addition to being immunomodulatory, Progesterone-Induced Blocking Factor (PIBF) plays a role in cell cycle regulation and invasion. The full length protein is associated with the pericentriolar satellites and as such, it is crucial for maintaining the integrity of spindle poles during mitosis. Another suggestive evidence for the involvement of PIBF in tumour progression is the fact that the PIBF gene has been identified on chromosome 13 in the region associated with breast cancer susceptibility. Earlier we showed that PIBF differentially regulates the invasiveness of trophoblast and tumour cell lines. The aim of the present study was to further investigate the role of PIBF in tumour development, using primary ovarian- (OC) and primary lung carcinoma (LC) cell cultures, and JEG-3 choriocarcinoma cell line. In the cultured cells PIBF was knocked down by siRNA treatment, and the impact of PIBF deficiency on MMP-9 activity and E-cadherin expression as well as on invasive and migratory capacity of the cells was tested. In conditioned media of PIBF-deficient JEG-3 cells, LC cells and OC cells MMP-9 activity was reduced to 36% 35%, and 65% respectively compared to controls. Though PIBF knock down did not affect migration, in JEG-3 cells, LC primary cells and OC primary cells PIBF deficiency resulted 20%, 50% and 50% decrease of invasion respectively. PIBF silencing resulted in increased E-cadherin expression, suggesting that by down regulating E-cadherin expression, PIBF might interfere with the cell-cell adhesion mechanisms and by increasing MMP activity induced extracellular matrix degradation, facilitates the invasion of tumour cells.

Human serum fetuin A/alpha2HS-glycoprotein level is associated with long-term survival in patients with alcoholic liver cirrhosis, comparison with the Child-Pugh and MELD scores.

BACKGROUND: Serum concentration of fetuin A/alpha2HS-glycoprotein (AHSG) is a good indicator of liver cell function and 1-month mortality in patients with alcoholic liver cirrhosis and liver cancer. We intended to determine whether decreased serum AHSG levels are associated with long-term mortality and whether the follow-up of serum AHSG levels can add to the predictive value of the Child-Pugh (CP) and MELD scores. METHODS: We determined serum AHSG concentrations in 89 patients by radial immunodiffusion. Samples were taken at the time of enrollment and in the 1st, 3rd, 6th, and the 12th month thereafter. RESULTS: Forty-one patients died during the 1-year follow-up period, 37 of them had liver failure. Data of these patients were analysed further. Deceased patients had lower baseline AHSG levels than the 52 patients who survived (293 +/- 77 vs. 490 +/- 106 microg/ml, mean +/- SD, p < 0.001). Of all laboratory parameters serum AHSG level, CP and MELD scores showed the greatest difference between deceased and survived patients. The cutoff AHSG level 365 microg/ml could differentiate between deceased and survived patients (AUC: 0.937 +/- 0.025, p < 0.001, sensitivity: 0.865, specificity: 0.942) better than the MELD score of 20 (AUC: 0.739 +/- 0.052, p < 0.001, sensitivity: 0.595, specificity: 0.729). Initial AHSG concentrations < 365 microg/ml were associated with high mortality rate (91.4%, relative risk: 9.874, 95% C.I.: 4.258-22.898, p < 0.001) compared to those with > or = 365 microg/ml (9.3%). Fourteen out of these 37 fatalities occurred during the first month of observation. During months 1-12 low AHSG concentration proved to be a strong indicator of mortality (relative risk: 9.257, 95% C.I.: 3.945-21.724, p < 0.001). Multiple logistic regression analysis indicated that decrease of serum AHSG concentration was independent of all variables that differed between survived and deceased patients during univariate analysis. Multivariate analysis showed that correlation of low serum AHSG levels with mortality was stronger than that with CP and MELD scores. Patients with AHSG < 365 microg/ml had significantly shortened survival both in groups with MELD < 20 and MELD > or = 20 (p < 0.0001 and p = 0.0014, respectively). CONCLUSION: Serum AHSG concentration is a reliable and sensitive indicator of 1-year mortality in patients with alcoholic liver cirrhosis that compares well to the predictive value of CP score and may further improve that of MELD score.

The use of a smartphone application for fast lung cancer risk assessment†.

OBJECTIVES: The overall prognosis of lung cancer is poor: Only every 8 patient survives 5 years after diagnosis. This outcome is partly attributable to late diagnosis. To implement a screening program for early diagnosis, selection of high-risk individuals is essential. Our aim was to construct a personalized lung cancer risk assessment tool using geographic localization to lead the high-risk individuals to the local health care provider. METHODS: A smartphone application was created for Android and iOS mobile platforms using a risk assessment questionnaire. The software provides immediate classification into low, moderate and high-risk groups. The high-risk group is directed to the nearest screening centre based on GPS location. The complete test data set is recorded on a collection server database for further analysis. RESULTS: The application was downloaded 13 890 times and completed by 89 500 persons over a period of 20 months. The mean age of the tested users was 36.91 years (9-93 years); the majority were men living in an urban area (62.3%). The test was completed by 38 850 active smokers and 26 710 persons who reported having already quit smoking, resulting in 30 072 moderate and 10 740 high-risk users. CONCLUSIONS: This free application is an active communication tool for most smartphone owners. It helps those who might need further medical attention. The affected users can be easily connected and localized via the smartphone, which helps recruit individuals into screening programs.

The in vitro effect of Garden Thyme (Thymus vulgaris L.) extract on Brachyspira hyodysenteriae.

Filtrates of a water extract of commercially available garden thyme (Thymus vulgaris L.) were used for studying its possible bactericidal effect on Brachyspira hyodysenteriae, the causative agent of swine dysentery, by agar-diffusion technique. Five of the six studied Brachyspira strains have proven to be sensitive and one moderately sensitive in the in vitro tests. It was concluded that water extract of garden thyme possesses inhibitory effects against B. hyodysenteriae. In vivo experiments are needed to check the validity of this conclusion.

[Effectiveness of mometasone furoate nasal spray in seasonal allergic rhinitis. First experiences in practice after the introduction of the drug in Hungary]. / Mometazon furoat orrspray hatékonyságának vizsgálata. A gyógyszer hazai bevezetését követó elsó pollenszezon gyakorlati tapasztalatai.

INTRODUCTION: The authors appraised the clinical efficacy of mometasone furoate in patients with seasonal allergic rhinitis and rhinoconjunctivitis. PATIENTS AND METHODS: An open, two-week trial was conducted in 89 patients between 1 July and 15 September 2001. A baseline oto-rhinolaryngological examination was performed. Nasal obstruction, rhinorrhea, sneezing, and itching as well as ocular, throat and ear clinical signs and general symptoms including cough and dyspnea were characterized using a symptom score. Mometasone furoate was administered intranasally in 100 micrograms doses into both nostrils. Depending on the severity of symptoms, antiallergic eye drops and systemic antihistamines were also allowed. After two weeks of treatment, a follow-up physical examination was performed and the symptom score was re-evaluated. Potential adverse events that had occurred during the treatment period were recorded. RESULTS: Mometasone furoate nasal spray alleviated all four nasal symptoms promptly and effectively. In particular, treatment resulted in a 93 percent decrease of overall symptom score. None of the participants discontinued treatment due to the occurrence of adverse effects. CONCLUSION: These results demonstrate that mometasone furoate nasal spray is a safe and effective intranasal corticosteroid for the therapy of SAR/SARC seasonal allergic rhinitis and rhinoconjunctivitis.

Alteration in the Wnt microenvironment directly regulates molecular events leading to pulmonary senescence.

In the aging lung, the lung capacity decreases even in the absence of diseases. The progenitor cells of the distal lung, the alveolar type II cells (ATII), are essential for the repair of the gas-exchange surface. Surfactant protein production and survival of ATII cells are supported by lipofibroblasts that are peroxisome proliferator-activated receptor gamma (PPARγ)-dependent special cell type of the pulmonary tissue. PPARγ levels are directly regulated by Wnt molecules; therefore, changes in the Wnt microenvironment have close control over maintenance of the distal lung. The pulmonary aging process is associated with airspace enlargement, decrease in the distal epithelial cell compartment and infiltration of inflammatory cells. qRT-PCR analysis of purified epithelial and nonepithelial cells revealed that lipofibroblast differentiation marker parathyroid hormone-related protein receptor (PTHrPR) and PPARγ are reduced and that PPARγ reduction is regulated by Wnt4 via a ß-catenin-dependent mechanism. Using a human in vitro 3D lung tissue model, a link was established between increased PPARγ and pro-surfactant protein C (pro-SPC) expression in pulmonary epithelial cells. In the senile lung, both Wnt4 and Wnt5a levels increase and both Wnt-s increase myofibroblast-like differentiation. Alteration of the Wnt microenvironment plays a significant role in pulmonary aging. Diminished lipo- and increased myofibroblast-like differentiation are directly regulated by specific Wnt-s, which process also controls surfactant production and pulmonary repair mechanisms.

Down-regulation of canonical and up-regulation of non-canonical Wnt signalling in the carcinogenic process of squamous cell lung carcinoma.

The majority of lung cancers (LC) belong to the non-small cell lung carcinoma (NSCLC) type. The two main NSCLC sub-types, namely adenocarcinoma (AC) and squamous cell carcinoma (SCC), respond differently to therapy. Whereas the link between cigarette smoke and lung cancer risk is well established, the relevance of non-canonical Wnt pathway up-regulation detected in SCC remains poorly understood. The present study was undertaken to investigate further the molecular events in canonical and non-canonical Wnt signalling during SCC development. A total of 20 SCC and AC samples with matched non-cancerous controls were obtained after surgery. TaqMan array analysis confirmed up-regulation of non-canonical Wnt5a and Wnt11 and identified down-regulation of canonical Wnt signalling in SCC samples. The molecular changes were tested in primary small airway epithelial cells (SAEC) and various lung cancer cell lines (e.g. A549, H157, etc). Our studies identified Wnt11 and Wnt5a as regulators of cadherin expression and potentiated relocation of ß-catenin to the nucleus as an important step in decreased cellular adhesion. The presented data identifies additional details in the regulation of SCC that can aid identification of therapeutic drug targets in the future.

Hereditary angioedema: a decade of human C1-inhibitor concentrate therapy.

BACKGROUND: C1-inhibitor (C1-INH) is a serine protease inhibitor regulating the complement, kinin-kallikrein, coagulation, and fibrinolytic systems. Hereditary angioedema (HAE) is caused by an inherited deficiency of C1-INH characterized by sudden, recurrent edematous swellings of the subcutaneous or submucosal tissues. The optional therapy for the acute management of HAE is administration of human C1-INH (hC1-INH) concentrate. However, hC1-INH is not available in many countries, in which case fresh frozen plasma is an alternative. OBJECTIVE: To summarize our experience with hC1-INH concentrate in patients with HAE. METHODS: Clinical and laboratory information on the effectiveness and safety of hC1-INH administered to relieve 468 acute edematous attacks in 61 patients with HAE was analyzed. RESULTS: Severe abdominal or subcutaneous attacks and laryngeal edema were consistently relieved by the administration of 500 U hC1-INH concentrate. Symptoms improved within 15 to 60 minutes of administration. Progression of the attacks was never observed, and there were no recurrent attacks within 72 hours. hC1-INH concentrate requirements did not change after repeated use. hC1-INH concentrate proved effective in the management of 94 attacks in 22 children and 6 attacks in 4 pregnant women. Adverse reactions, viral infections, and antibody formation against the purified protein did not occur. CONCLUSION: The administration of hC1-INH concentrate in HAE is highly effective and safe for the treatment of acute attacks and short-term prophylaxis and in pediatric patients and pregnant women. CLINICAL IMPLICATIONS: Human C1-INH concentrate is effective and safe for the treatment of acute HAE attacks as well as for short-term prophylaxis.