Human SLFN5 is a transcriptional co-repressor of STAT1-mediated interferon responses and promotes the malignant phenotype in glioblastoma.

We provide evidence that the IFN-regulated member of the Schlafen (SLFN) family of proteins, SLFN5, promotes the malignant phenotype in glioblastoma multiforme (GBM). Our studies indicate that SLFN5 expression promotes motility and invasiveness of GBM cells, and that high levels of SLFN5 expression correlate with high-grade gliomas and shorter overall survival in patients suffering from GBM. In efforts to uncover the mechanism by which SLFN5 promotes GBM tumorigenesis, we found that this protein is a transcriptional co-repressor of STAT1. Type-I IFN treatment triggers the interaction of STAT1 with SLFN5, and the resulting complex negatively controls STAT1-mediated gene transcription via interferon stimulated response elements. Thus, SLFN5 is both an IFN-stimulated response gene and a repressor of IFN-gene transcription, suggesting the existence of a negative-feedback regulatory loop that may account for suppression of antitumor immune responses in glioblastoma.

Anti-inflammatory effects of atorvastatin treatment in chronic obstructive pulmonary disease. A controlled pilot study.

UNLABELLED: Observational studies have suggested that statins may have beneficial effects on outcomes in chronic obstructive pulmonary disease (COPD) patients. These effects may be mediated through an anti-inflammatory effect of statins. The purpose of this pilot-study was to determine whether statins have an anti-inflammatory effect on the lungs of COPD patients. We conducted randomized, controlled, parallel group pilot-study to compare the effects of atorvastatin (n=12) or placebo (n=6) on lung inflammation in patients with mild to moderate COPD. The primary endpoint was change in CD45+ cells expression measured by immunohistochemistry and changes in expression of genes measured using microarrays in lung biopsy (TBB) samples before and after 12 weeks of treatment with atorvastatin 40 mg/day. All subjects had spirometry, lung volumes, diffusing capacity of the lungs for carbon monoxide (DLCO), St George's Respiratory Questionnaire (SGRQ), 6 minute walk distance (6 MWD), serum lipids, hs-CRP, induced sputum (IS), bronchoscopy and TBB carried out at baseline and after treatment. TBB specimens were processed for histology, immunohistochemistry and genome-wide association studies (GWAS) profiling. Seventeen subjects completed the study. There was a significant improvement in SGRQ with mean SGRQ decreased by 12 points after treatment with atorvastatin (P=0.012). Atorvastatin treatment produced a significant 34% reduction in sputum neutrophil count, and a 57% reduction in CD45+ cells in lung biopsies (expressed as integrated optical density -IOD; median IOD 62.51% before, 27.01% after atorvastatin treatment, P=0.008). In patients' lung tissue atorvastatin treatment produced downregulation of key genes involved in inflammatory processes, immune response, and leukocyte activation. These data demonstrate the pulmonary anti-inflammatory effects of atorvastatin in COPD patients with the potential for beneficial clinical effects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01748279.

Usefulness of automatic measurement of contrast flow intensity: an innovative tool in contrast-enhanced ultrasound imaging of atherosclerotic carotid plaque neovascularization. A pilot study.

AIM: Contrast-enhanced ultrasound imaging of the carotid arteries (CECU) permits direct, real-time visualization of neovascularization in atherosclerotic plaques and is a confirmed predictor of unstable atheromatous lesions. The aim of the study was the assessment of a new, automatically measured index of intensity in quantitative estimation of the contrast flow through the carotid plaque (till now assessed only visually). METHODS: Forty-four patients (mean age 70.4±11.4) with ultrasound diagnosed significant stenosis of internal carotid artery (ICA), after cerebrovascular or cardiovascular events, qualified for carotid artery stenting (CAS) were examined. The carotid ultrasound examinations with contrast agent Sonovue were performed. RESULTS: Visually in 22 patients (50%) contrast flow through the atherosclerotic plaques was found. In 17 patients (38.6%) massive, calcified atherosclerotic plaques were present. Patients with preserved contrast flow through the plaque more frequently had a history of cerebral stroke (P=0.04). Massive calcifications of atherosclerotic plaques correlated with a previous MI (P=0.03) and the degree of advancement of coronary artery disease (P=0.04), but not with a previous cerebral stroke. Contrast flow through the atherosclerotic plaque positively correlated with values of the index of intensity (r=0.69, P<0.00001). In patients with preserved contrast flow the mean value of the index of intensity was 22.24±3.55 dB as compared with 12.37±7.67 dB - a value present in patients without preserved contrast flow. No significant relation for the degree of calcifications and the value of the index of intensity was found. CONCLUSION: The assessment of the index of intensity is a novel, simple and automatic method to estimate the degree of contrast flow through the carotid plaque. The values of the index of intensity correlate with the contrast flow through the atherosclerotic plaque, but not with its calcification.

The importance of intima-media thickness (IMT) measurements in monitoring of atherosclerosis progress after myocardial infarction.

PURPOSE: Intima-media thickness (IMT) assessed in peripheral arteries correlates with presence and progression of atherosclerosis in coronary arteries. IMT measurements may help to select high risk patients and evaluate the efficacy of the therapy used. AIM: The aim of the study was to assess the usefulness of ultrasonographic measurement of IMT in atherosclerosis progress monitoring in patients after myocardial infarction (MI). PATIENTS AND METHODS: 70 men (mean age 52.8 ± 8.4) treated with PCI due to acute myocardial infarction, were enrolled in the study. All subjects underwent ultrasound examination of the IMT complex of: common carotid artery (CCA), carotid bulb and common femoral artery (CFA) during hospitalization and follow-up period (3.83 ± 1.29 years). RESULTS: During the follow-up 3 patients (4.3%) were not on any medications, 8 pts (11.4%) were on reduced doses of ß-blocker, statin or ACE-I (non-compliant pts.). The others (compliant) - 59 pts (84.3%) received standard pharmacological treatment after MI. Nevertheless, an increase of IMT complex value after follow-up compared to initial IMT values of all examined peripheral arteries was observed (respectively: IMT CCA - 0.91 ± 0.26 vs 1.10 ± 0.36, p=0.002, IMT of carotid bulb - 1.31 ± 0.55 vs 1.82 ± 0.69, p=0.012, IMT CFA - 1.38 ± 0.64 vs 1.97 ± 0.75, p=0.014). Non-compliant patients had statistically significant higher IMT values after follow-up when compared to compliant subjects (1.62 vs 1.20, p= 0.017). Patients with higher IMT values were reported to have cardiac events more frequently during the follow-up (p<0.05). CONCLUSIONS: Our results provide evidence that ultrasonographic IMT complex assessment of peripheral arteries in everyday clinical practice allows monitoring efficacy of pharmacological therapy in CAD patients after MI. They also suggest treatment intensification if necessary.

Adiponectin--an independent marker of coronary artery disease occurrence rather than a degree of its advancement in comparison to the IMT values in peripheral arteries.

OBJECTIVE: The aim of the study was to establish whether adiponectin may act as an independent risk factor of coronary artery disease (CAD) and if adiponectin has potential relations with a new marker of cardiovascular risk -intima-media thickness (IMT). METHODS: 165 patients, who had undergone coronary angiography due to symptoms of CAD were enrolled. Selected clinical and biochemical risk factors were assessed, adiponectin concentrations and IMT were measured. RESULTS: A significantly lower adiponectin concentrations in the CAD group, as compared to the controls, were found. Adiponectin concentration did not correlate with a degree of coronary vessels changes advancement. No correlation between adiponectin concentrations and IMT values in the studied peripheral arteries were found. The value of 9.8 ug/ml has been assigned as a cut-off value. Adiponectin concentrations <9.8 µg/ml had the highest positive predictive value (PPV=95.7%) and specificity (90.9), but low sensitivity (30.8). In the multilogistic regression analysis significant variables influencing the appearance of CAD were found: HDL-C (p=0.011, OR=0.88, 95%CI 0.80-0.97), IMT in CCA (p=0.0048, OR=5.25, 95%CI 1.65-16.75), IMT in CFA (p=0.015, OR=1.65, 95%CI 1.10-2.48 ), and adiponectin concentration <9.8 µg/ml (p=0.032, OR=28.95, 95%CI 1.31-641.48). CONCLUSIONS: Adiponectin is an independent risk factor of coronary artery disease occurrence, but not its advancement. No correlation between adiponectin concentration and IMT values in peripheral arteries was shown.

Intima-media thickness is a useful marker of the extent of coronary artery disease in patients with impaired renal function.

OBJECTIVE: The aim of the study was the assessment of intima-media thickness (IMT) in peripheral arteries (the carotid and the femoral artery) and its correlation with the extent of coronary artery disease (CAD). The second task was the analysis of the renal function's influence within IMT complex. METHODS: 231 patients (men, mean age 52.8), who had undergone coronary angiography due to symptoms of CAD were enrolled. The ultrasound measurement of IMT in the common carotid artery (CCA), carotid bulb and common femoral artery (CFA) was performed. The relationship between IMT, renal function and the extent of CAD was evaluated. RESULTS: Significantly higher values of IMT in the peripheral arteries were observed in patients with CAD than in those without (CCA-0.91 vs 0.61 mm, carotid bulb-1.31 vs 0.67, CFA-1.38 vs 0.63 respectively, p<0.0001). The GFR values in the CAD patients significantly negatively correlated with IMT complex in CCA (p<0.001) and carotid bulb (p<0.05). Lower values of GFR in patients with three-vessel disease were observed than in those patients with one- or two-vessel disease (p<0.05). In multifactoral analysis (post-hoc NIR test) we found that glomerular filtration rate (GFR) is strongly determined by age (p<0.0001), BMI (p<0.0001), value of carotid intima-media thickness (p<0.001), value of IMT in the carotid bulb (p<0.02) and the treatment with ACE-I (p<0.05). In multifactoral analysis we did not find any statistical influence of lipid profile and glucose disturbances on GFR. CONCLUSIONS: Higher peripheral artery IMTs in patients with CAD than in those without and patients with three-vessel disease indicate that IMT may be used as an early marker of atherosclerosis and reflect the severity of CAD. A significant negative correlation between the value of a GFR and the IMT confirmed the usefulness of this noninvasive method for the estimation of preclinical stages of atherosclerotic changes' development in patients with impaired renal function.

Thrombin activatable fibrinolysis inhibitor (TAFI) in stable angina pectoris patients undergoing coronary artery bypass grafting (CABG).

PURPOSE: Thrombin activatable fibrinolysis inhibitor (TAFI) seems to be a potential haemostatic risk factor of coronary artery disease (CAD). Taking into account interactions between TAFI and haemostasis, especially during cardiopulmonary bypass, we decided to determine concentration of TAFI and activated TAFI (TAFIa) and other haemostasis markers in CABG patients. MATERIAL AND METHODS: 45 CAD patients (11 women, 34 men) undergoing elective CABG were included in the study. Blood samples were taken before the operation, on the 3rd, 7th day and 3 months after CABG. A value of p<0.05 was considered statistically significant. RESULTS: We found a significant decrease in TAFIa concentration on 3rd postoperative day: 6 microg/ml (0.3-43.2) vs 8.9 microg/ml (0.5-37) before CABG (p<0.05), a significant increase in TAFI concentration on the 7th postoperative day: 127.7% +/- 36.8 vs 112.18% +/- 30.34 of standard plasma concentration before CABG (p<0.05), significant increase in plasmin-antyplasmin (PAP) complexes concentration on 3rd and 7th day, respectively: 645 microg/l (323-1237) vs 406 microg/l (197-1840) before CABG (p<0.001); and 1030 microg/l (640-2149) vs 406 microg/l (197-1840) before CABG (p<0.0001). Before operation we found a significant negative correlation between PAP complexes concentration before CABG and EuroSCORE risk scale value (p<0.01). CONCLUSIONS: In CABG patients, there is a significant increase in fibrinolytic activity due to decrease in TAFIa concentration, with simultaneous increase in PAP complexes. A significant negative correlation between PAP complexes concentration before CABG and EuroSCORE risk scale value stressed a potentially higher operation risk in patients with lower fibrinolytic activity.

Cardiac surgical treatment of the patients with renal insufficiency.

Cardiac surgical treatment of the patients with renal insufficiency became more frequent necessity. Also postoperative renal insufficiency occurs pretty often after cardiac surgery. That is in part a result of broadening of operative indications, which might concern patients with multiple diseases. Patients with renal insufficiency and coexistent heart diseases, patients with endocarditis and patients with renal insufficiency after cardiac surgery require the treatment of cardiac surgeons and nephrologists. Heart diseases are the main cause of the mortality in the dialysis patients. Among the patients with renal diseases the cardiac surgeon most often receive long-term dialysis patients with coexistent heart diseases, who needs cardiac surgery (coronary artery by-pass grafting, valve operations). The amount of these operations increases, however it does not exceed 1% of overall number of cardiac operations. This group however, is very exacting and carries a high operative risk. Dialysis patients are exposed to increased risk of infection. 75% of them reveal infections in the form of sepsis. The presence of bacteria in the bloodstream increase the risk of infectious endocarditis. 6% of dialysis patients with IE require surgery. The prevention of renal failure after cardiac surgery is also very important. Renal insufficiency occurs in 12% of patients after cardiac surgery with the use of extracorporeal circulation. Renal failure complicates postoperative course and is of high risk for the patient. The mortality due to acute postoperative renal failure, which requires hemofiltration, reaches 70%. The proper cardiac surgical and nephrological management of renal insufficiency in patients selected for cardiac surgery as well as in patients with postoperative renal insufficiency is necessary to obtain good operative results.

[The effectiveness of conservative treatment of cervical lesions using the LLETZ and CO2 laser]. / Skutecznosc oszczedzajacego leczenia zmian szyjki macicy przy zastosowaniu procedury LLETZ oraz waporyzacyjnego lasera CO2.

Development made on the carcinogenesis process of the cervical lesions and increased detection of the early precancerous lesions enable discontinuance of radical treatments for non-radical techniques which it is of vital importance to young women of the child-bearing capacity. The aim of this study was to determine the efficacy of the non-radical treatment of the cervical lesions using LLETZ procedure (Large Loop Excision of Transition Zone) and laser CO2 vaporisation. 2046 women aged 18-46 who were diagnosed for cervical lesions were treated in the Institute of Obstetrics and Gynaecology Medical School of Bialystok in the years 1994-97. 216 of which were histologically confirmed for CIN I-III diagnosis. The choice between LLETZ or laser CO2 was made based on a pre-treatment examination (cytology, colposcopy, microbiology test and punch biopsy). The final results were evaluated from 6 months to 4 years after the treatment. The effectiveness of CO2 laser was 94.6% and was similar to LLETZ--96.4%. In spite of almost complete agreement in both procedures, the LLETZ seems to be more preferred because of the possibility of histological post-treatment verification.