Cigarette smoke (CS) is a well-established risk factor to cardiovascular health and the most preventable cause of death. Countless studies have demonstrated its harm to health and many more studies investigating its pathogenic mechanisms. While the CS-induced pathogenic mechanism of cardiovascular dysfunction has been mainly attributed to a combination of oxidative imbalance, vascular endothelial dysfunction, inflammation and modification of lipid profile, the focus of the current study was on the mediators of inflammation and the activation of signal pathways. In this study, we investigated the effects of CS on the pro-inflammatory/anti-inflammatory status in the heart and to elucidate the activation of specific signaling pathways in an in vivo rat model. Male Sprague-Dawley rats were divided into groups of CS exposure and sham air (SA) and exposed to 1 hour of respective CS and SA exposure daily for 56 days. The rats were then sacrificed and the ventricular homogenates were examined. Cardiac pro- inflammatory and anti-inflammatory mediators such as C-reactive protein (CRP), interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (CINC-1), transforming growth factor (TGF)-β1, vascular endothelial growth factor (VEGF) and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA) and the activation of specific signaling pathways was determined by Western blot analysis. CS caused suppression of cardiac CRP, IL-6, TGF-β1, and IL-10 and elevation of VEGF, revealing the imbalance of pro-inflammatory/anti-inflammatory status. Nuclear factor-κB (NF-κB) was also activated along with the activation of extracellular-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) but not p38 mitogen-activated protein kinase (MAPK) after 56 days of CS exposure. These data suggests the presence of a local adaptive mechanistic response to modulate cardiac pro-inflammatory/anti-inflammatory status via NF-κB/MAPK pathways after exposure to CS. These findings shed insight into the mechanistic pathways of CVD progression, allowing possible identification of selected mediators as biomarkers that could benefit early detection of CVD arisen from cigarette smoking. / published_or_final_version / Pharmacology and Pharmacy / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Pharmacology / Master / Master of Philosophy

The purpose of this research was to compare and contrast the components and characteristics of selected widely available smoking cessation programs.To reach this goal, an evaluation form was developed after an extensive review of the literature which addressed the structure, duration, techniques, issues which were discussed, success rates and availability of the programs. This form was tested for content validity by a jury of experts and was used to review each of thirteen selected smoking cessation programs. The reviews were conducted by the author using program materials received from the sponsoring organizations. Any questions which could not be answered with these materials were answered through a telephone interview with a representative of the sponsoring organization.Once the reviews were completed, the information was transferred to table form and to a database so that collective data could be generated. The following conclusions were drawn from the table and the data generated: the existing smoking cessation programs appear to have been developed utilizing suggestions offered in to use similar program techniques, and a great deal of variance exists in terms of success rates and cost. / Department of Physiology and Health Science

Indiana University-Purdue University Indianapolis (IUPUI) / The complex pathogenesis of emphysema involves disappearance of alveolar structures, in part attributed to alveolar cell apoptosis. The mechanism by which cigarette smoke (CS) induces alveolar cell apoptosis is not known. We hypothesized that ceramides are induced by CS via specific enzymatic pathways that can be manipulated to reduce lung cell apoptosis. CS increased ceramides in the whole lung and in cultured primary structural lung cells. Exposure to CS activated within minutes the acid sphingomyelinase, and within weeks the de novo- ceramide synthesis pathways. Pharmacological inhibition of acid sphingomyelinase significantly attenuated CS-induced apoptosis. To understand the mechanisms by which ceramides induce apoptosis, we investigated the cell types affected and the involvement of RTP801, a CS-induced pro-apoptotic and pro-inflammatory protein. Direct lung augmentation of ceramide caused apoptosis of both endothelial and epithelial type II cells. Ceramide upregulated RTP801 and the transgenic loss of RTP801 inhibited only epithelial, but not endothelial cell apoptosis induced by ceramide. In conclusion, CS induces acid sphingomyelinase-mediated ceramide upregulation and apoptosis in a cell-specific manner, which in epithelial cells involves induction of stress response proteins that may further amplify lung injury. Molecular targeting of amplification pathways may provide therapeutic opportunities to halt emphysema progression.

M. S.

M.S.

published_or_final_version / Pharmacology / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / toc / Community Medicine / Doctoral / Doctor of Philosophy

The structural and functional integrity of a developing and maturing fetal and neonatal lung is critically dependent on carbohydrate metabolism. The energy derived from carbohydrate metabolism is utilized during the processed of cell growth and development. It is reported that maternal nicotine exposure during pregnancy and lactation results in the irreversible inhibition of glycolysis, for which no mechanism is currently proposed and a significant increase in glucose turnover. The principal objective of this thesis was to determine the influence of maternal nicotine exposure during gestation and lactation on the isoenzyme patterns and transcript levels of the selected enzymes in developing neonatal rat lung, in an attempt to elucidate the mechanism of inhibition of glycolysis observed.