Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 “functional” binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules

Cholesteatoma - the Neoangiogenesis in Adults and Children

Оbjective: The aim of the current study was: to detect the presence of large and newly form small blood vessels in chronic inflammation of cholesteatoma and to evaluate the role of VEGF and CD-31 in triggering of angiogenesis in chronic inflammation of cholesteatoma in adults and childrenMaterial & Methods: The CD-31- positive blood vessels and the level of expression of VEGF were determined by immunohistochemistry 16 archival biopsies which from patients with adults cholesteatoma and 5 patients with pediatric cholesteatomaResults: CD31-positive blood vessels in the granulation tissue of cholesteatoma were more numerous than the vessels in the adjacent normal skin of the auditory meatus; VEGF-positive blood vessels in the granulation tissue cholesteatoma are more numerous that the vessels in the adjacent normal skin of the auditory meatus.Conclusion: The observed increased angiogenesis in granulation tissue of cholesteatoma might be triggered by the increased expression of VEGF which is secreted by many structures and cells in perimatrix of cholesteatoma. The studies characteristics of the active angiogenesis were markedly enhanced in the biopsies from congenital cholesteatoma form. The results suggest the important role of angiogenesis in the growth of cholesteatoma and in aggressiveness of congenital pediatric typeKey words: Cholesteatoma, Adults, Children, Angiogenesis, VEGF, CD-3

Association of the MMP7 –181A>G promoter polymorphism with early onset of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is characterized by decreased air flow and is associated with abnormal chronic inflammation in the airways and extensive tissue remodeling. Matrix metalloproteinase-7 (MMP7) is produced primarily by the epithelium of many organs, including the lungs. A functional MMP7 –181A>G (rs11568818) promoter polymorphism influences the binding of nuclear regulatory proteins modulating the transcription of the gene. In this study, we genotyped 191 patients with COPD for MMP7 –181A>G single nucleotide polymorphism (SNP) and 215 control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and explored the role of that polymorphism as a risk factor for COPD. There were no differences in the genotype and allele distribution of the MMP7 –181A>G SNP between the COPD patients and control groups (p = 0.341 and p = 0.214). However, the carries of the G allele (AG and GG genotypes), appeared to develop COPD significantly earlier than those with the AA genotype (61.01 ± 10.11 vs. 64.87 ± 9.00 years, p = 0.032). When the genotype distribution was studied only in the groups of patients (n = 76) and controls (n = 106) younger than 60 years, we found significantly higher frequency of the carriers of the G allele in COPD patients than in the controls, determining about a 3-fold higher risk for COPD [odds ratio (OR) –3.33, 1.36-8.14, p = 0.008 for GG, and OR = 2.91, 1.38-6.13, p = 0.005 for AG+GG]. Based on our results, the MMP7 –181A>G promoter variant may influence early development of COPD. This effect could be attributed to the increased production of the enzyme resulting in enhanced airway wall protein degradation and injury

Clinical Significance of the Combination of Intraoperative Lavage and Continuous Antibiotic Peritoneal Lavage in Patients with Peritonitis

Background and Aim: The aim of our study is to determine the clinical significance of a combination of intraoperative and postoperative continuous closed lavage with antibiotic (PCLA) in patients with severe peritonitis.Materials and Methods: We analyzed 187 patients with severe peritonitis for a period of 10 years - 89 (47.6%) with total and 98 (52.4%) with diffuse peritonitis. All included patients were with clinical signs of sepsis and ICU treatment was needed. We performed peritoneal lavage during the surgical intervention in all patients, but PCLA was used in 98 (52.4%) of the patients. In all patients, we observed: amount of fluid, need of relaparotomy, duration of systemic antibiotic application and mortality. Results: We found significant statistical association between morbidity, mortality, and the amount of fluid, used for intraoperative and PCLA - patients who needed volume over 4 liters for intraoperative lavage were with high morbidity and mortality (p-0.0001; p-0.003, respectively) and PCLA with volume under 4 l was related to lower rate of complications and better outcome (p-0.0056). The mean duration of systemic antibiotical application in patients with PCLA was 7.45 days ± 2.61 against 12.6 days ± 3.5 without lavage (p-0.0093). The rate of relaparotomy was lower in patients with PCLA (p-0.0029). The mortality in the study reached 8.02% (n-15). Four of the 15 patients (26.6%) with unfavorable outcome were treated with PCLA (p-0.002). Independent predictors of mortality were: volume for lavage over 4 l (p-0.000), relaparotomy (p-0.002), need for PCLA over 72 hours (p-0.006). Conclusion: The application of PCLA is an effective therapeutic option for reduction of the relaparotomy rate and mortality in complicated patients with severe peritonitis