Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2005. Directed by Boris Mizaikoff. / Hunt, William, Committee Member ; Weck, Marcus, Committee Member ; Mizaikoff, Boris, Committee Chair ; Janata, Jiri, Committee Member ; Orlando, Thomas, Committee Member. Includes bibliographical references.

Thesis (Ph.D)--Civil and Environmental Engineering, Georgia Institute of Technology, 2007. / Committee Chair: Dr. Armistead G Russell; Committee Member: Dr. James A. Mulholland; Committee Member: Dr. Michael Chang; Committee Member: Dr. Randall L. Guensler; Committee Member: Dr. Yuhang Wang. Part of the SMARTech Electronic Thesis and Dissertation Collection.

Diss. med. dent. Zürich. / Sonderdruck aus: Schweizer Monatsschrift für Zahnmedizin. Bd. 118, Nr. 6, 2009. Literaturverz.

Diss. med. dent. Zürich. / Sonderdruck aus: Schweizer Monatsschrift für Zahnmedizin. Bd. 118, Nr. 6, 2009. Literaturverz.

Cigarette smoking (CS) represents the main causative agent underlying development and progress of COPD. Recently, involvement of CS in the pathogenesis of COPDassociated muscle abnormalities is becoming increasingly evident. Nevertheless, involved triggers and underlying mechanisms remain largely unknown. This study was conceived in order to examine effects of cigarette smoke exposure on skeletal muscle morphology, vascular supply and function. For this purpose, we have specifically designed murine COPD/emphysema model and gastrocnemius muscle was examined, while in vitro experiments were conducted using murine C2C12 skeletal muscle myocytes. In addition to the mild emphysematous changes present in the lungs of CS-exposed mice, our results demonstrated evident signs of muscle atrophy reflected by decreased fiber cross-sectional area, profound fiber size variation and reduced body mass. Furthermore, we have observed impairment in terminal myogenesis and lower number of myonuclei in skeletal muscles of CS-exposed animals despite evident activation of muscle repair process. Additionally, our results demonstrate capillary rarefaction in skeletal muscles of CS-exposed animals which was associated with deregulation of hypoxia-angiogenesis signaling, reduced levels of angiogenic factors such as HIF1-α and VEGF and enhanced expression of VHL and its partner proteins PHD2 and Ube2D1. The results of our in-vitro experiments demonstrated that VHL and its ubiquitination machinery can be synergistically regulated by TNF and hypoxia consequentially impairing angiogenic potential of skeletal muscle myocytes. Finally, we have shown that CS elicits chronic ER stress in murine skeletal muscles which is associated with activation of ERAD and apoptotic pathways as mirrored by elevated expression of Usp19, caspase 12 and caspase 3 in skeletal muscles of CSexposed animals. Moreover, molecular and morphological alterations in CS-exposed mice resulted in impairment of muscle function as reflected by their impaired exercise capacity. Taken together, from our results it is evident that cigarette smoke exposure elicits set of morphological, vascular and functional changes highly resembling those observed in COPD. Additionally, CS induces wide range of molecular alterations and signaling pathway deregulations suggesting profound effects of cigarette smoke exposure on skeletal muscle cell homeostasis.

University of Macau / Faculty of Science and Technology / Department of Electromechanical Engineering

Streptococcus pneumoniae is a common human pathogen, causing severe and often life-threatening respiratory tract infections. Even though most patients receive appropriate antimicrobial chemotherapy, a significant percentage still die. Cigarette smoking is a well-documented risk factor for severe pneumococcal pneumonia; however, the microbiological/ immunological mechanisms which predispose smokers to infection are not yet completely understood. The pneumococcal toxin, pneumolysin, is a major virulence factor of S. pneumoniae; it forms pores in eukaryotic cell membranes, resulting in the influx of extracellular Ca2+. Biofilm is a self-generated polymer matrix, used by microbial pathogens to isolate themselves from both host defences, as well as antibiotics. In this dissertation, the effects of cigarette smoke condensate (CSC) on the bioactivity of pneumolysin, as well as on the growth of, and production of biofilm by Streptococcus pneumoniae are described. A clinical isolate of S. pneumoniae, strain 172, was used for both growth and biofilm determinations in the presence or absence of concentrations of CSC (20-160 μg/ml), representative of the smoking habit. Growth and biofilm determinations were performed using spectrophotometric procedures, viability by standard colony forming unit procedures, and the effect of the condensate on pneumolysin bioactivity using a fura-2/AM-based spectrofluorometric procedure. Exposure of the pneumococcus to CSC resulted in a dose-dependent increase in biofilm formation which achieved statistical significance (P≤0.05) at concentrations of 80 and 160 μg/ml, in the setting of modest effects on bacterial growth. These findings were not unique to S. pneumoniae since exposure of Staphylococcus aureus, a known biofilm former, to CSC showed similar results. Exposure of pneumolysin to CSC (20 and 40 μg/ml) was accompanied by attenuation of the biological activity of the toxin, resulting in impaired pore-forming ability manifest as a considerable reduction in influx of extracellular Ca2+ following exposure of isolated neutrophils to the toxin. It is possible that CSC acts as a stressor to the bacteria, thereby enhancing biofilm formation and consequently persistence in the respiratory tract. These effects of the toxin may be complemented by inactivation of pneumolysin, presumably by pro-oxidative mechanisms, affecting innate cellular host defences. These mechanisms may underpin the predisposition of smokers to develop severe pneumococcal infections. / AFRIKAANS : Streptococcus pneumoniae is ‘n algemene menslike patogeen, wat ernstige en soms lewensbedreigende lugweg infeksies veroorsaak. Alhoewel die meeste pasiënte geskikte antimikrobiese chemoterapie ontvang, sterf ‘n betekenisvolle hoeveelheid steeds. Sigaretrook is ‘n welbekende risikofaktor vir ernstige pneumokokkale pneumonie; die mikrobiologiese/ immunologiese meganisme wat rokers vatbaar maak vir infeksie word egter nog nie heeltemal verstaan nie. Die pneumokokkale toksien, pneumolisien, is ‘n belangrike virulensie faktor van S. pneumoniae; dit vorm porieë in die eukariotiese selmembrane wat ‘n invloei van ekstrasellulêre Ca2+ tot gevolg het. Biofilm is ‘n self-genererende polimeermatriks, wat deur mikrobiese patogene gebruik word om hulself teen gasheerverdedigings meganismes en antibiotika te isoleer. In hierdie verhandeling word die uitwerking van sigaretrook kondensaat (SRK) op die bioaktiwiteit van pneumolisien, asook die effekte op groei en die produksie van biofilm deur S. pneumoniae, beskryf. ‘n Kliniese isolaat van S. pneumoniae, stam 172, is gebruik vir beide groei en biofilm bepalings, in die teenwoordigheid en afwesigheid van SRK (20-160 μg/ml), wat verteenwoordigend van die rook gewoonte is. Groei en biofilm bepalings is uitgevoer deur gebruik te maak van spektrofotometriese prosedures, lewensvatbaarheid, deur standard kolonievormende eenheid prosedures, en die effek van die kondensaat op die pneumolisien bioaktiwiteit, deur fura-2/AM-gebaseerde spektrofluorometriese prosedures. Blootstelling van die pneumokokkus aan SRK het in ‘n dosis-verwante verhoging in biofilm-formasie tot gevolg gehad, wat statistiese betekenisvolheid (P≤0.05) bereik het teen konsentrasies van 80 en 160 μg/ml, teenoor die agtergrond van beskeie effekte op bakteriële groei. Hierdie bevindinge is nie uniek aan S. pneumoniae nie, aangesien blootstelling van Staphylococcus aureus, ‘n bekende biofilm-vormer, aan SRK soortgelyke resultate gelewer het. Blootstelling van pneumolisien aan SRK (20-160 μg/ml) was geassosieer met die verswakking van die biologiese aktiwiteit van die toksien, met verminderde porie-vormende vermoë, wat gemanifesteer het met ‘n ongelooflike verlaging in die invloei van ekstrasellulêre Ca2+ na die blootstelling van geïsoleerde neutrofiele aan die toksien. Dit is moontlik dat die SRK as ‘n stressor vir die bakterieë optree, en daardeur biofilm formasie en gevolglik hardnekkige infeksies in die lugweg tot sellulêre gasheervededing beïnvloed. Hierdie effekte op die toksien mag gekomplimenteer word deur die inaktivering van pneumolisien, heelwaarskynlik deur pro-oksidatiewe meganismes, wat die vatbaarheid van rokers om ernstige pneumokokkale infeksies te ontwikkel, beklemtoon. / Dissertation (MSc)--University of Pretoria, 2011. / Immunology / Unrestricted

Background: According to the partial smoke-free legislation implemented on 1 September 2010 in Guangzhou, China, smoke-free did not cover all indoor areas. Some places have a full smoking ban (100 % smoke-free), other places have a partial smoking ban, and homes have no ban. This study aimed to compare the smoking behaviors before and after implementation of a smoke-free legislation. Method: A repeated cross-sectional survey was conducted on smoking-related behaviors with a total of 4,900 respondents before, and 5,135 respondents after the legislation was instituted. For each wave of the survey, a three-stage stratified sampling process was used to obtain a representative sample. Pearson's Chi-square test was used to determine differences of smoking prevalence and quit ratio between the two samples. Logistic regression models were used to examine the associations of a smoke-free legislation with smoking behaviors. Results: The overall daily smoking rate declined significantly from 20.8 % to 18.2 % (p∈<∈0.05), especially among those aged 15-24 years. The quit ratios increased significantly (from 14.5 % to 17.9 %), but remained low among 15-44 year olds. The overall self-reported smoking behaviors in locations with a full smoking ban decreased significantly from 36.4 % to 24.3 % with the greater drops occurring in cultural venues, public transport vehicles, and government offices. Smoking in places with partial smoking bans remained high (89.6 % vs. 90.4 %), although a slight decrease was observed in some of these areas. The implementation of a smoke-free legislation did not lead to more smoking in homes (91.0 % vs 89.4 %), but smoking in homes remained high. Conclusions: These findings highlight the urgent need for a comprehensive smoke-free legislation covering all public places in Guangzhou, simultaneously educational interventions and campaigns promoting voluntary changes in home smoking need to occur.

The dangers of secondhand smoke (SHS) exposure on the human body were initially reported in 1972, just eight years after the negative effects of smoking on smokers was reported. The Surgeon General of the United States systematically expanded (and continues to expand) the warnings over time, as new scientific evidence becomes available. Warnings, which began to incorporate youths in 1975, emphasized the need to pay particular attention to fetuses, newborns, infants, children, adolescents, and young adults since they rely on parents, guardians, and other adults to keep them safe. Although fewer in number than adults, the diseases that are causally linked to smoking and exposure to SHS in youths are also complex and can result in death (i.e., sudden infant death syndrome). The introduction of new tobacco products, such as low nicotine cigarettes and electronic cigarettes, prompted the Surgeon General to release additional warnings. In 2016, the Surgeon General advised the nation that more information will become available as the electronic cigarette manufacturers comply with new Tobacco Control Act requirements to report harmful vapor constituents. Physicians need to keep abreast of the vast and growing body of knowledge related to the biological and chemical components of SHS and vapor, as well as the dangers that SHS and vapor cause. To ease the burden on physicians, the federal government and medical professional societies created clinical practice guidelines which summarize the literature related to the dangers of SHS and make recommendations for medical management. Guidelines recommend that physicians and other clinicians should offer smoking cessation advice and intervene to limit youth exposure to SHS. Although the approach recommended for use with patients in a physician’s office is clear and attempts to streamline the processes have been made, the identification and counseling process for smoking cessation and eliminating SHS exposure remains time consuming. Barriers to payment make it difficult for physicians to be adequately reimbursed for their efforts to keep their patients safe from the dangers of SHS and vapor exposure. More work is needed to be able to continue to reduce the percentage of youths exposed to SHS in their environments. Additional attention is needed to address the racial and ethnic disparities that are evident in the scientific literature.

No description available.