CD4+CD25+ FOXP3-positive T-regulatory cells have an important role in controlling immune and inflammatory reactions. The present authors hypothesise that these cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to characterise the expression of FOXP3 in large and small airways of nonsmokers, smokers with normal lung function and COPD patients.A total of 19 nonsmokers, 20 smokers with normal lung function and 20 smokers with moderate COPD, undergoing lung resection for a solitary peripheral nonsmall cell carcinoma, were enrolled in the study. Immunohistochemical methods were used to evaluate FOXP3 expression in large and small airways.Smokers with normal lung function and COPD patients had increased numbers of FOXP3-positive cells in large airways compared with nonsmokers. A positive correlation was observed between FOXP3 expression in large airways and smoked pack-yrs. In small airways, COPD patients had decreased numbers of FOXP3-positive cells, compared with asymptomatic smokers and nonsmokers, that negatively correlated with airflow obstruction.To conclude, chronic obstructive pulmonary disease is characterised by upregulation of FOXP3-positive cells in large airways but a downregulation in small airways that correlated with airflow limitation. The results of the present study contribute to a better understanding of the pathogenesis of chronic obstructive pulmonary disease.

BackgroundTransarterial embolization (TAE) is a therapeutic option for patients with a high risk of recurrent bleeding after endoscopic haemostasis. The aim of our prospective study was a preliminary assessment of the safety, efficacy, and clinical outcomes following preventive TAE in patients with non-variceal acute upper gastrointestinal bleeding (NVUGIB) with a high risk of recurrent bleeding after endoscopic haemostasis.MethodsPreventive visceral angiography and TAE were performed after endoscopic haemostasis on patients with NVUGIB who were at a high risk of recurrent bleeding (PE+ group). The comparison group consisted of similar patients who only underwent endoscopic haemostasis, without preventive TAE (PE− group). The technical success of preventive TAE, the completeness of haemostasis, the incidence of rebleeding and the need for surgical intervention and the main outcomes were compared between the groups.ResultsThe PE+ group consisted of 25 patients, and the PE− group of 50 patients, similar in age (median age 66 vs. 63 years), gender and comorbid conditions. The ulcer size at endoscopy was not significantly different (median of 152 mm vs. 127 mm). The most frequent were Forest II type ulcers, 44% in both groups. The distribution of the Forest grade was even. The median haemoglobin on admission was 8, 2 g/dl vs. 8,7 g/dl, p = 0,482, erythrocyte count was 2,7 × 1012/L vs. 2,9 × 1012/L, p = 0,727. The shock index and Rockall scores were similar, as well as and transfusion – on average, four units of packed red blood cells for the majority of patients in both groups, however, significantly more fresh frozen plasma was transfused in the PE− group, p = 0,013. The rebleeding rate was similar, while surgical treatment was needed notably more often in the PE- group, 8% vs. 35% accordingly, p = 0,012. The median ICU stay was 3 days, hospital stay – 6 days vs. 9 days, p = 0.079. The overall mortality reached 20%; in the PE+ group it was 4%, not reaching a statistically significant difference.ConclusionPreventive TAE is a feasible, safe and effective minimally invasive type of haemostasis decreasing the risk of repeated bleeding and preparing the patient for the definitive surgical intervention when indicated.

Azidothymidine, a nucleoside-analogue reverse transcriptase inhibitor (NRTI), is a commonly used antiretroviral drug in AIDS treatment, however its use is limited by severe toxic side effects due to its influence on mitochondria that result in myopathy, particularly affecting the cardiac muscle. We suggest that effective protection of azidothymidineinduced cardiopathology can be expected from drugs that are capable of targeting mitochondria. Therefore the present study in mice was carried out with mildronate, a cardioprotective drug of the aza-butyrobetaine class, which previously has been shown to act as a highly potent protector of mitochondrial processes. In our study, saline (control), azidothymidine (50 mg/kg), mildronate (50, 100 and 200 mg/kg), and azidothymidine π mildronate (at the doses mentioned) were injected intraperitoneally daily in separate groups of mice for two weeks. At the termination of the experiment, mice were sacrificed, the hearts were removed and cardiac tissue was examined morphologically and immunohistochemically. It was found that azidothymidine, compared to control and mildronate groups, induced major morphologic changes in cardiac tissue, which were manifestated as degeneration and inflammation. These changes were prevented when mildronate was co-administered with azidothymidine. Mildronate also reduced the azidothymidine-induced expression of nuclear factor kBp65 (NF-kBp65). The obtained data demonstrate a high ability of mildronate of preventing azidothymidine-induced cardiopathologic changes, and suggest mildronate's indirect action on azidothymidine-caused oxidative stress reactions leading to mitochondrial dysfunction. This offers a rational combination of mildronate with azidothymidine or other anti-HIV drugs for beneficial application in AIDS therapy.

Background Upper gastrointestinal bleeding (UGIB) due to peptic ulcer disease is one of the leading causes of death in patients with non-variceal bleeding, resulting in up to 10% mortality rate, and the patient group at high risk of rebleeding (Forrest IA, IB, and IIA) often requires additional therapy after endoscopic hemostasis. Preventive transarterial embolization (P-TAE) after endoscopic hemostasis was introduced in our institution in 2014. The aim of the study is an assessment of the intermediate results of P-TAE following primary endoscopic hemostasis in patients with serious comorbid conditions and high risk of rebleeding. Methods During the period from 2014 to 2018, a total of 399 patients referred to our institution with a bleeding peptic ulcer, classified as type Forrest IA, IB, or IIA with the Rockall score ≥ 5, after endoscopic hemostasis was prospectively included in two groups—P-TAE group and control group, where endoscopy alone (EA) was performed. The P-TAE patients underwent flow-reducing left gastric artery or gastroduodenal artery embolization according to the ulcer type. The rebleeding rate, complications, frequency of surgical interventions, transfused packed red blood cells (PRBC), amount of fresh frozen plasma (FFP), and mortality rate were analyzed. Results From 738 patients with a bleeding peptic ulcer, 399 were at high risk for rebleeding after endoscopic hemostasis. From this cohort, 58 patients underwent P-TAE, and 341 were allocated to the EA. A significantly lower rebleeding rate was observed in the P-TAE group, 3.4% vs. 16.2% in the EA group; p = 0.005. The need for surgical intervention reached 10.3% vs. 20.6% in the P-TAE and EA groups accordingly; p = 0.065. Patients that underwent P-TAE required less FFP, 1.3 unit vs. 2.6 units in EA; p = 0.0001. The mortality rate was similar in groups with a tendency to decrease in the P-TAE group, 5.7% vs. 8.5% in EA; p = 0.417. Conclusion P-TAE is a feasible and safe procedure, and it may reduce the rebleeding rate and the need for surgical intervention in patients with a bleeding peptic ulcer when the rebleeding risk remains high after primary endoscopic hemostasis.