Long-term effects of immunosuppressive therapy on lung function in scleroderma patients.

The study aims to analyze the effects of induction treatment with cyclophosphamide (CYC) pulse therapy followed by maintenance treatment with other mild immunosuppressive agents on lung function in scleroderma (SSc) patients. Thirty patients with SSc (mean age 52 years, mean disease duration < 2 years) with forced vital capacity (FVC) ≤ 80% and/or diffusing capacity of carbon monoxide (DLco) ≤ 70% were included. Monthly CYC pulses were given for 6 months (induction treatment), followed by 3-monthly maintenance pulses for the next 18 months, and during the next 5 years patients received other mild immunosupressive therapy brought by the competent rheumatologist. The efficacy was evaluated by comparing FVC% and DLco% after 6, 24, and 84 months from the baseline. All patients completed induction and maintenance treatment with CYC. Three patients were lost to follow-up. The rest of 27 patients, during the next 5 years, received other immunosupressive agents (14 azathioprine, 9 methotrexate, and 4 mycophenolate mofetil). Three patients died in the 4 years of follow-up. By 6, 24, and 84 months, the mean FVC and DLco changes were + 0.47 and + 2.10, + 3.30 and - 2.49, and + 1.53 and - 3.76%, respectively. These changes were not significantly different from the baseline values. CYC does not appear to result in clinically significant improvement of pulmonary function but fulfilled criteria of stable disease. Maintenance treatment with other mild immunosupressive agents preserves the benefits achieved during CYC treatment.

Oxidative stress markers predict early left ventricular systolic dysfunction after acute myocardial infarction treated with primary percutaneous coronary intervention.

BACKGROUND: Despite successful primary percutaneous coronary intervention (PCI) after ST-segment elevation myocardial infarction (STEMI), some patients develop left ventricular systolic dysfunction (LVSD) and acute heart failure (HF). Identifying patients with an increased risk of developing LVSD by means of biomarkers may help select patients requiring more aggressive therapy. OBJECTIVES: The aim of this study was to evaluate the relationship between the levels of oxidative stress markers and development of LVSD and acute HF early after STEMI. MATERIAL AND METHODS: The study enrolled 148 patients with the first STEMI, who were treated by primary PCI < 12 h from the onset of symptoms. We assessed the impact of different biomarkers for developing LVSD and acute HF (Killip ≥ 2) including: markers of necrosis - peak creatine kinase (CK), markers of myocardial stretch - B-type natriuretic peptide (BNP), inflammatory markers - C-reactive protein (CRP), leucocyte and neutrophil count, as well as oxidative stress markers - total thiol groups, catalase, superoxide dismutase (SOD) and glutathione reductase (GR). RESULTS: In multivariate analysis, thiol groups, peak CK, anterior wall infarction, and age were predictors of LVEF ≤ 40%. Out of 16 variables significantly associated with the Killip ≥ 2 in univariate logistic regression analysis, 5 appeared to be independently associated with acute HF in multivariate analysis: catalase, BNP, leucocytes, neutrophil count, and size of left atrium. CONCLUSIONS: In this study, we have shown for the first time that thiol groups and catalase are independent predictors of STEMI complication - LVSD and acute HF, respectively. Beside routine used biomarkers of necrosis and myocardial stretch, thiol groups and catalase may provide additional information regarding the risk stratification.

In vitro and in vivo antimelanoma effect of ethyl ester cyclohexyl analog of ethylenediamine dipropanoic acid.

Melanoma, an aggressive skin tumor with high metastatic potential, is associated with high mortality and increasing morbidity. Multiple available chemotherapeutic and immunotherapeutic modalities failed to improve survival in advanced disease, and the search for new agents is ongoing. The aim of this study was to investigate antimelanoma effects of O,O-diethyl-(S,S)-ethylenediamine-N,N'di-2-(3-cyclohexyl) propanoate dihydrochloride (EE), a previously synthesized and characterized organic compound. Mouse melanoma B16 cell viability was assessed using acid phosphatase, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, sulforhodamine B, and lactate dehydrogenase assays. Apoptosis and autophagy were investigated using flow cytometry, fluorescence and electron microscopy, and western blotting. In vivo antitumor potential was assessed in subcutaneous mouse melanoma model after 14 days of treatment with EE. Tumor mass and volume were measured, and RT-PCR was used for investigating the expression of autophagy-related, proapoptotic, and antiapoptotic molecules in tumor tissue. Investigated organic compound exerts significant cytotoxic effect against B16 cells. EE induced apoptosis, as confirmed by phosphatidyl serine externalisation, caspase activation, and ultrastructural features typical for apoptosis seen on fluorescence and electron microscopes. The apoptotic mechanism included prompt disruption of mitochondrial membrane potential and oxidative stress. No autophagy was observed. Antimelanoma action and apoptosis induction were confirmed in vivo, as EE decreased mass and volume of tumors, and increased expression of several proapoptotic genes. EE possesses significant antimelanoma action and causes caspase-dependent apoptosis mediated by mitochondrial damage and reactive oxygen species production. Decrease in tumor growth and increase in expression of proapoptotic genes in tumor tissue suggest that EE warrants further investigation as a candidate agent in treating melanoma.

[Cerebrospinal fluid amyloid beta and tau protein: biomarkers for Alzheimer's disease].

BACKGROUND/AIM: Introduction of acetylcholine esterase inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has additionally highlighted the importance of diagnostic markers in cerebrospinal fluid (CSF) for early AD diagnosis: low level of 42 amino acid form of amyloid-beta peptide (Abeta42), and levels of tau protein (T-tau) and phosphorylated tau protein (P-tau). The aim of this study was to diagnostic potential of CSF biomarkers T-tau, P-tau and Abeta42 as biochemical markers for AD. METHODS: Lumbar puncture was performed in 63 patients with AD and 26 control subjects who passed orthopedic surgery. The Innotest, ELISA sandwich test (Innogenetics - Belgium) was used for measuring the levels of T-tau, P-tau and Abeta342. RESULTS: The patients and the control group did not differ in age, education and sex. Mean levels of CSF T-tau and P-tau were significantly higher in the patients with AD (p < 0.001) compared to the control group, in contrast to significantely lower CSF Abeta42 in AD group (p < 0.001). A significant progressive decrease of Abeta42, as well as significant progressive increase of T-tau and P-tau was found among AD subgroups (according to MMSE staging) and controls. CONCLUSION: The obtained results suggest that these biomarkers may be supportive in the diagnosis of AD, especially in the early course of the disease and could be used in the routine clinical practice considering the approaching target therapeutics.