Smoking, Respiratory Diseases and Endothelial Dysfunction

Vascular endothelium actively participates in inflammatory reactions in the majority of chronic respiratory diseases. Smoking is a major risk factor for bronchopulmonary diseases, and it plays an important role in endothelial dysfunction development. Some experiments prove that aggressive pollutants of tobacco smoke (benzopyrene, peroxynitrite, acrolein, cyanides, peroxides, etc.) can cause direct damage to endothelial cells due to expression of adhesion molecules on their surface and intensification of lipid peroxidation. In turn, oxidized lipoproteins in the tunica intima of the vessel work as attractants for chemotaxis of leukocytes and monocytes that start to produce pro-inflammatory cytokines in big amounts. These processes trigger systemic inflammatory response that leads to irreversible thickening of the vessel walls and deterioration of their mechanical properties. Chronic exposure to tobacco smoke and the products of combustion of tobacco leads to chronic system inflammatory reaction, oxidative stress, endothelial dysfunction and morpho-functional damage of target organs. Nowadays, the connection between chronic obstructive pulmonary disease (COPD) and some cardiovascular and cerebrovascular diseases has been well established. Studying the mechanisms of endothelial dysfunction in brain blood vessels of patients with smoking habits and COPD can be very important for preventing acute vascular events

Smoking and COPD: Endothelium-Related and Neuro-mediated Emphysema Mechanisms

This chapter describes endothelium-related and neuro-mediated mechanisms of emphysema development in chronic obstructive pulmonary disease (COPD) and smoking on the basis of previously completed studies, literature data, and own researches. As components of neurogenic inflammation in the processes of tissue remodeling in emphysema, we describe the distribution and activity of the substance P, neurokinin-1 and its receptor, tissue metalloproteinases and their tissue inhibitors in the lungs during the entire experimental period, the modeling of COPD in rats with a smoking model. We also analyzed the content of neurokinin system markers, the localization, and markers of tissue metalloproteinases in human lung tissue structures. We have confidence that there is a special morphofunctional continuum of development of lower respiratory tract remodeling in response to chronic exposure to tobacco smoke and the development of inflammation in COPD. New data suggest that imbalance of neuro-mediated interactions, alteration of vasomotoric signaling mechanisms, secretion, mucociliary clearance, cytoprotection involving substance P-dependent components with impaired content, and development of dystopia of matrix metalloproteinases and their tissue inhibitors are involved in the initiation of morphological restructuring. Research in this direction should be continued to allow approaches to the development of preventive and therapeutic strategies for emphysema

Сопоставление информативности МР-перфузии и ПЭТ с [11С]метионином в дифференциации продолженного роста церебральных опухолей и лучевых поражений головного мозга после комбинированного лечения

The aim of the study was to compare T2*-weighted MR-perfusion (pMRI) and positron emission tomography using [11C]methionine (PET-Met) in differentiating recurrent brain tumor (RT) from posttreatment radiation effect (PTRE). Material and methods. PET-Met and pMRIwere performed in 45 patients with previously treated brain tumor A total 57 lesions were analyzed. The rCBV index and [11C] methionine uptake index (UI-Met) were calculated as the ratios of the highest lesion value to the that in the reference region. The diagnostic accuracy of UI-Met and rCBV for correct identification of recurrent tumor (RT) versus PTRE was evaluated by ROC-analysis using subsequent histologic analysis or clinical and radiological follow-up. Results. According to the final diagnosis patientsexhibitedthetwo typesofabnormalities: recurrent tumor (n = 33) and non-progressive lesions (n = 24). The inter-individual agreement between the both techniques was observed in 93% of cases. In 4 patients results were discordant. High [11C]methionine uptake and low rCBV were detected in 2 cases of radiation necrosis. In 2 patients PET-Met was able to distinguish foci of radionecrosis and the viable tumor tissue. Conclusion. T2*-weighted MR-perfusion and PET-Met could be efficiently used for differentiation RT from PTRE. Inter-individual comparison of the both methods showed that PET-Met was more sensitive in imaging recurrent tumor, but perfusion MRI had higher specificity.Цель исследования: сравнительный анализ результатов Т2* МР-перфузии (пМРТ) и позитронно-эмиссионной томографии с [11С]метионином (ПЭТ-Мет) в дифференциальной диагностике продолженного роста опухоли (ПРО) и лучевого повреждения головного мозга (ЛП). Материал и методы. ПЭТ-Мет и пМРТ были выполнены 45 пациентам после комбинированного лечения церебральных опухолей. Было проанализировано 57 контрастно-позитивных очагов, для каждого из которых вычислялся индекс накопления [11С]метионина и индекс rCBV. Верификация результатов базировалась на патогистологическом исследовании (n = 20) или динамическом клинико-радиологическом наблюдении (n = 24). Для определения информативности выбранных показателей и оптимальных величин для принятия решения использован ROC-анализ. Результаты. Согласно окончательному диагнозу, пациенты были разделены на 2 группы: группа ПРО (n = 33) и группа с отсутствием ПРО (n = 24). Совпадение результатов ПЭТ и пМРТ наблюдали в 93% случаев. У 4 пациентов отмечалось расхождение результатов. В 2 случаях лучевого поражения определялось высокое накопление метионина при пониженных значения rCBV. У других 2 больных ПЭТ позволила выявить участок активной опухолевой ткани на фоне постлучевых изменений. Выводы. nМРТ и ПЭТ-Мет могут быть эффективно использованы для дифференциации ПРО и ЛП головного мозга. Сопоставление результатов показало, что ПЭТ-Мет обладает большей чувствительностью в выявлении и контурировании границ ПРО, но уступает по специфичности nМР