The effect of collagen,Interleukin-l α and glicosaminoglycan on the neovascularization of central nervous system

Abstract

Neovascularization, the development of a new microvasculature, has an important role in physiological and pathological processes. The vascular changes in the brain can be easily detected because the proliferation of endothelial cells in its vascular structure is quite small, and so constitutes a good model for neovascularization studies. In the present investigation, to induce intracerebral neovascularization, we implanted collagen, Interleukin-l alpha (IL-lα) and glicosaminoglycan into the brain ofpigs, in order to test the hypothesis that IL-l α, collagen and glicosaminoglycan play a pivotal. role in the process of neovascularization. Both pure collagen and collagen combined with IL-l a induced neovascularization according to light-electron microscopic findings and values of enzymes' activities. In particular, collagen combined with IL-lα synergically affected the increase of neovascularization. However, glicosarrinoglycan did not affect it significantly. Although the results of this study provided us with some interesting data indicating the beneficial effects of collagen combined with IL-1α on neovascularization, further studies should be done to study the short term effect of these biochemical substances. [Neural Res 1998; 20: 513-525]     

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Planning and managing a complex multisite study in the age of technology

A 2‐year long, multisite research study that evaluated cardiopulmonary resuscitation skill decay among nursing students was conducted at 10 schools of nursing across the United States. The study was conducted in two phases and required carefully timed sessions for skill performance. Multisite studies in nursing education need to be carefully planned. Time delays should be anticipated with processes and Institutional Review Board protocols across sites. All team members were trained and consistently supported during the entire study. While challenges and obstacles were identified, innovative solutions were implemented that assisted the research team to successfully complete the study. The use of new and existing technology allowed the team to surmount many of the challenges encountered in this study. The purpose of this article is to describe the logistics, processes, challenges, and lessons learned related to conducting a complex multisite study.     

Effectiveness and safety of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet combination among HIV-infected patients in Turkey: results from a real world setting

BackgroundEfficacy of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil (E/C/F/TDF) in treatment-naïve and experienced patients with HIV infection was demonstrated in phase 3 trials. The primary objective of this study was to evaluate effectiveness and safety of E/C/F/TDF in real world settings.MethodsRetrospective, observational data collected by the Turkish ACTHIV-IST study group between May 2015 and December 2016 were analysed.ResultsA total of 387 patients were prescribed E/C/F/TDF; 210 patients with available data at 6th month were eligible; 91.5% were male, and mean age was 35.2 (SD: 10.8) years; 54.0% of males identified themselves as MSM. Sixty-three percent (133) of the study population were treatment-naïve patients, and 37% (77) were treatment experienced. HIV RNA level was below 100 copies/mL in 78.9% of treatment-naïve patients and 89.9% of treatment experienced patients at month 6. Median increase in CD4 T lymphocyte count was 218 copies/mL in treatment-naïve patients and remained stable or increased in treatment experienced patients. Adverse events were observed in 15% of the patients, and the regimen was discontinued in only six patients.ConclusionReal world data on the effectiveness and safety of E/C/F/TDF is comparable with the phase 3 trial results Adverse events are uncommon and manageable.     

Differential proteolytic activity and induction of apoptosis in fibrous versus atheromatous plaques in carotid atherosclerotic disease

PURPOSE: Atherosclerotic plaque instability may be a contributing factor to plaque complications, such as rupture, thrombosis, and embolization. Of the two types of plaques, atheromatous and fibrous, the atheromatous type has been reported to be vulnerable and unstable. This instability may be related to changes in the cell cycle and extracellular matrix degradation. Apoptosis may weaken the plaque structurally. In addition, alteration of the cellular component may lead to imbalances in associated proteolytic activity. Our study was designed to compare the two types of plaques in terms of apoptosis, apoptosis-inducing factors, namely Fas/CD95/APO-1 and CPP-32/YAMA/caspase-3, and proteolytic activity. METHODS: Carotid artery plaques were obtained from patients undergoing endarterectomy and were classified as either atheromatous or fibrous on the basis of established criteria. Histologic study included hematoxylin and eosin staining, Verhoeff's van Gieson elastin staining, and trichrome staining. Detection of apoptosis was performed with the TUNEL assay. Immunohistochemical studies were performed to localize the expression of CPP-32/YAMA and Fas/CD95. Gelatin gel zymography was used to compare proteolytic activity levels in the two types of plaque. RESULTS: Apoptosis was significantly higher (P <.001) in atheromatous plaques (4.90% +/- 1.27% [SEM]) as compared with fibrous plaques (0.86% +/- 0.46% [SEM]). Zymography demonstrated elevated levels of proteinases in atheromatous plaques. Immunohistochemistry revealed significant increases in the expression of Fas/CD95 (P <.04) and CPP-32/YAMA (P <.001) in atheromatous plaques as compared with that in fibrous plaques. CONCLUSIONS: This is the first study comparing molecular factors that render atheromatous plaques more susceptible to rupture than fibrous plaques. The higher number of apoptotic cells seen in atheromatous plaques as compared with fibrous plaques could contribute to their greater instability. Immunoreactivity to cytoplasmic death domain, Fas/CD95 and CPP-32/YAMA, a prominent mediator of apoptosis, was consistent with the numbers of apoptotic cells detected. The increased levels of proteolytic activity in atheromatous plaques may make these plaques more prone to rupture. These data identifying some of the molecular events and biochemical pathways associated with plaque vulnerability may help in the development of new strategies to prevent plaque rupture.     

Programmed Cell Death (Apoptosis) and Its Role in the Pathogenesis of Lower Extremity Varicose Veins

p < 0.03). This increased apoptotic activity was not observed in media or intima of either vein group (p < 0.001). No significant difference in immunoreactivity to bcl-2 protein was observed in varicose vein specimens as compared to controls. Varicose vein specimens demonstrated increased nuclear expression of cyclin D1 whereas its cytoplasmic expression was significantly diminished (p≤0.02). These data show that programmed cell death is inhibited in varicose veins. Differential expression of cyclin D1 suggests that it may deregulate cell cycle events, thereby leading to varicosity formation.