Tobacco – Smoke separator or treater – By chemical reaction – e.g. – ion-exchange – chelating,...
Reexamination Certificate
2001-11-15
2004-09-14
Walls, Dionne A. (Department: 1731)
Tobacco
Smoke separator or treater
By chemical reaction, e.g., ion-exchange, chelating,...
C131S331000
Reexamination Certificate
active
06789546
ABSTRACT:
FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to methods of preventing or reducing pathogenesis of oxidant stress-associated diseases of the aerodigestive tract. More particularly, the present invention relates to methods of employing hydroxocobalamin (vitamin B12a, OH—CO), deferoxamine (DES) and reduced glutathione (GSH) to reduce or prevent tobacco smoke (TS)-induced cellular or macromolecular damage in the aerodigestive tract.
Harmful Effects of Tobacco Consumption:
The deleterious effects of tobacco abuse, principally via cigarette smoking, are well known. Tobacco is a worldwide public health hazard accounting for significant morbidity and mortality. Although smoking places an abundant oxidant insult to the oropharynx and respiratory tract, the oxidant burden is deleterious to the entire body of the tobacco consumer. Namely, tobacco consumption leads to development or enhancement of atherosclerosis, cardiovascular disease, chronic obstructive pulmonary disease and various forms of cancer, including carcinomas of the mouth, pharynx, esophagus and lung.
There are three principal ways to consume tobacco: smoking, chewing and dipping and snuffing. Approximately 50 million Americans smoke and countless others are affected by tobacco smoke (TS) as secondary smokers. Children of smokers breathe this second-hand smoke and have more respiratory problems than children of non-smokers. Smokeless tobacco is used by as many as 12 million individuals and has a detrimental effect on the oral cavity plus systemic effects from buccal absorption of nicotine and other chemicals. Chewing looseleaf tobacco and “dipping” moist, ground snuff tobacco are common uses of tobacco without smoking.
Studies have estimated that TS has over 3,000 different constituents, of which many are toxic, carcinogenic and/or generate free radical species. Free radicals are atoms or molecules containing an unpaired electron. Oxygen free radicals include the superoxide free radical (.O2
−
) and the hydroxyl radical (OH.) which, together with hydrogen peroxide (H
2
O
2
) and singlet oxygen (
1
O2), are jointly called reactive oxygen species (ROS). Due to their high reactivity they may lead to chemical modification and impairment of the components of living cells, such as proteins, lipids, carbohydrates and nucleotides.
Tobacco smoke mediated oxidant injury is similar to that induced by smog, thereby increasing such noxious stimuli to primary and secondary smokers in polluted atmospheric environments.
Most of constituents of TS have been identified in so-called mainstream and side stream TS. The former is that volume of smoke drawn through the mouthpiece of the tobacco product during puffing while side stream smoke is that smoke emitted from the smoldering cigarette in between puffs. Although tar and nicotine are retained in the filter of cigarettes, this applies mainly to mainstream smoke, when comparing filter and non-filter cigarettes. Mainstream smoke emission is also markedly reduced both in low and in ultra low tar yield cigarettes. However, the emissions of toxic and carcinogenic components in side stream smoke are not significantly reduced in filter cigarettes when compared to non-filter counterparts. Thus, side stream smoke is a major contributor to environmental smoke, affecting both the smoker and their non-smoking counterparts, so called secondary smokers.
Evidence shows that cigars as well as cigarettes are highly toxic and addictive. Tobacco smokers have a similar increased risk for oral and laryngeal cancers. Evidence indicates that one cigar generates levels of carcinogenic particles exceeding those generated by three cigarettes. Fumes from cigars are also of greater consequence to secondary smokers. Epidemiologic studies reveal greater frequencies of heart disease, emphysema, and cancers of the mouth and pharynx in cigar smokers when compared to matched non-smokers. Cigar smokers may spend one full hour smoking a single large cigar and commonly hold an unlit cigar in the mouth, allowing further exposure to toxins by local absorption. Thus, consumption of cigars may produce an equal or greater burden of toxic exposure to TS than cigarettes. Recently, sales of cigars have risen, partly due to their gaining popularity with women and the advent of the female friendly “cigar bar”.
Oral Diseases Associated With Tobacco Consumption: Tobacco, whether smoked or chewed, causes common untoward effects in the oral cavity. Tobacco smoke has two chances to exert its deleterious effects in the mouth; when it is inhaled by the smoker and on its exit during exhalation.
Over 30,000 new cases of cancer of the oral cavity are diagnosed annually, accounting for 2-4 percent of all new cancers. Oral cancer kills 8,000 patients each year and only half of cases diagnosed annually have a five-year survival. The great majority of these patients are users of tobacco products. Oral squamous cell carcinoma (SCC) is the most common malignancy of the head and neck with a worldwide incidence of over 300,000 new cases annually. The disease is characterized by a high rate of morbidity and mortality (approximately 50%) and in this respect is similar to malignant melanoma (1-4). The major inducer of oral SCC is exposure to tobacco which is considered to be responsible for 50-90% of cases world-wide (5, 6). As such, the incidence of oral SCC in tobacco smokers is 4-7 times higher than in non-smokers (7, 8). Moreover, the higher TS-related risk for oral SCC is manifested by a reduction in the mean age of development of the disease by 15 years as compared to non-smokers (9).
Leukoplakia, a tobacco induced white patch on the buccal mucosa, as found in smokers, is a localized irritation due to direct contact of smoked or smokeless tobacco and it is directly related to the frequency and years of tobacco abuse. Although leukoplakia is a benign oral lesion, it has a malignant potential.
In addition, tobacco contributes to other oral symptoms or pathologies of the mouth and teeth. Tobacco may cause halitosis, may numb the taste buds, and interfere with the smell and the taste of food. It may stain teeth and contribute to dental caries. Smokers have more dental tartar (calculus) than non-smokers. Tobacco is associated also with destructive periodontal (gum) disease and tooth loss. Acute necrotizing ulcerative gingivitis (“trench mouth”) is a destructive, painful inflammatory condition occurring mainly in tobacco smokers. Swelling of the nasal and sinus membranes have also been associated, purportedly, in individuals who are “allergic” to TS.
Oral submucous fibrosis occurs mainly in India and is a chronic, progressive premalignant condition. The etiology is chronic chewing of tobacco or areca nut or both. The fibrosis results in restriction of mouth opening and involves the palates, tonsillar fossa, buccal mucosa and underlying muscle. Associated with this condition is also oropharyngeal carcinomas, also with a high frequency in India and associated in 70% of cases with chewing tobacco. Smokeless tobacco and areca nut usage is also common in Pakistan, Bangladesh and Java and in these and Indian immigrants to the United States and United Kingdom.
Tobacco smoke also affects the skin adversely. Dr. Douglas Model of England in 1985 added to the medical lexicon the term “smoker's face” from a study with pictures of 116 cases and suitable non-smoking controls (10). Akin to photodamage, those with smoker's face appear older and have more wrinkles.
Molecular Damage Resulting From Exposure to TS: Tobacco smoke induces oxidative damage to lipids, DNA and proteins, particularly via protein-SH groups as a consequence of containing high levels of both free radicals as well as aldehydes, including acetaldehyde (ethanol), propanol and acrolein, as well as other deleterious molecules.
Oxidant Injury: Tobacco smoke is divided into two phases; tar and gas-phase smoke. Tar contains high concentrations of free radicals. Many tar extracts and oxidants are water-soluble and reduce oxygen to superoxide radical which can dismutate to f
Klein Ifat
Nagler Rafael M.
Reznick Abraham Z.
G. E. Ehrlich (1995) Ltd.
Technion Research & Development Foundation Ltd.
Walls Dionne A.
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