Interaction of alcohol and smoking in the pathogenesis of upper digestive tract cancers - possible chemoprevention with cysteine

Background: Alcohol consumption and smoking are the main causes of upper digestive tract cancers. These risk factors account for over 75% of all cases in developed countries. Epidemiological studies have shown that alcohol and tobacco interact in a multiplicative way to the cancer risk, but the pathogenetic mechanism behind this is poorly understood. Strong experimental and human genetic linkage data suggest that acetaldehyde is one of the major factors behind the carcinogenic effect. In the digestive tract, acetaldehyde is mainly formed by microbial metabolism of ethanol. Acetaldehyde is also a major constituent of tobacco smoke. Thus, acetaldehyde from both of these sources may have an interacting carcinogenic effect in the human upper digestive tract. Aims: The first aim of this thesis was to investigate acetaldehyde production and exposure in the human mouth resulting from alcohol ingestion and tobacco smoking in vivo. Secondly, specific L-cysteine products were prepared to examine their efficacy in the binding of salivary acetaldehyde in order to reduce the exposure of the upper digestive tract to acetaldehyde. Methods: Acetaldehyde levels in saliva were measured from human volunteers during alcohol metabolism, during tobacco smoking and during the combined use of alcohol and tobacco. The ability of L-cysteine to eliminate acetaldehyde during alcohol metabolism and tobacco smoking was also investigated with specifically developed tablets. Also the acetaldehyde production of Escherichia coli - an important member of the human microbiota - was measured in different conditions prevailing in the digestive tract. Results and conclusions: These studies established that smokers have significantly increased acetaldehyde exposure during ethanol consumption even when not actively smoking. Acetaldehyde exposure was dramatically further increased during active tobacco smoking. Thus, the elevated aerodigestive tract cancer risk observed in smokers and drinkers may be the result of the increased acetaldehyde exposure. Acetaldehyde produced in the oral cavity during ethanol challenge was significantly decreased by a buccal L-cysteine -releasing tablet. Also smoking-derived acetaldehyde could be totally removed by using a tablet containing L-cysteine. In conclusion, this thesis confirms the essential role of acetaldehyde in the pathogenesis of alcohol- and smoking-induced cancers. This thesis presents a novel experimental approach to decrease the local acetaldehyde exposure of the upper digestive tract with L-cysteine, with the eventual goal of reducting the prevalence of upper digestive tract cancers.

Helicobacter pylori: resistance and treatment results in Finland

Background: Helicobacter pylori infection is usually acquired in early childhood and is rarely resolved spontaneously. Eradication therapy is currently recommended virtually to all patients. While the first and second therapies are prescribed without knowing the antibiotic resistance of the bacteria, it is important to know the primary resistance in the population. Aim: This study evaluates the primary resistance of H. pylori among patients in primary health care throughout Finland, the efficacy of three eradication regimens, the symptomatic response to successful therapy, and the effect of smoking on gastric histology and humoral response in H. pylori-positive patients. Patients and methods: A total of 23 endoscopy referral centres located throughout Finland recruited 342 adult patients with positive rapid urease test results, who were referred to upper gastrointestinal endoscopy from primary health care. Gastric histology, H. pylori resistance and H. pylori serology were evaluated. The patients were randomized to receive a seven-day regimen, comprising 1) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and metronidazole 400 mg t.d. (LAM), 2) lansoprazole 30 mg b.d., amoxicillin 1 g b.d. and clarithromycin 500 mg b.d. (LAC) or 3) ranitidine bismuth citrate 400 mg b.d., metronidazole 400 mg t.d. and tetracycline 500 mg q.d. (RMT). The eradication results were assessed, using the 13C-urea breath test 4 weeks after therapy. The patients completed a symptom questionnaire before and a year after the therapy. Results: Primary resistance of H. pylori to metronidazole was 48% among women and 25% among men. In women, metronidazole resistance correlated with previous use of antibiotics for gynaecologic infections and alcohol consumption. Resistance rate to clarithromycin was only 2%. Intention-to-treat cure rates of LAM, LAC, and RMT were 78%, 91% and 81%. While in metronidazole-sensitive cases the cure rates with LAM, LAC and RMT were similar, in metronidazole resistance LAM and RMT were inferior to LAC (53%, 67% and 84%). Previous antibiotic therapies reduced the efficacy of LAC, to the level of RMT. Dyspeptic symptoms in the Gastrointestinal Symptoms Rating Scale (GSRS) were decreased by 30.5%. In logistic regression analysis, duodenal ulcer, gastric antral neutrophilic inflammation and age from 50 to 59 years independently predicted greater decrease in dyspeptic symptoms. In the gastric body, smokers had milder inflammation and less atrophy and in the antrum denser H. pylori load. Smokers also had lower IgG antibody titres against H. pylori and a smaller proportional decrease in antibodies after successful eradication. Smoking tripled the risk of duodenal ulcers. Conclusions: in Finland H. pylori resistance to clarithromycin is low, but metronidazole resistance among women is high making metronidazole-based therapies unfavourable. Thus, LAC is the best choice for first-line eradication therapy. The effect of eradication on dyspeptic symptoms was only modest. Smoking slows the progression of atrophy in the gastric body.

The influence of school smoking policy and school prevention programs on the smoking behaviour of high school students in Prince Edward Island, Canada

The aim of the study was to examine the influence of school smoking policy and school smoking prevention programs on the smoking behaviour of students in high schools in Prince Edward Island using the School Health Action Planning Evaluation System (SHAPES). A total sample included 13,131 observations of students in grades 10-12 in ten high schools in Prince Edward Island over three waves of data collection (1999, 2000, and 2001). Changes in prevalence of smoking and factors influencing smoking behaviour were analyzed using descriptive statistics and Chi-Square tests. Multi-level logistic regression analyses were used to examine how both school and student characteristics were associated with smoking behaviour (I, II, III, IV). Since students were located within schools, a basic 2-level nested structure was used in which individual students (level 1) were nested within schools (level 2). For grade 12 students, the combination of both school policies and programs was not associated with the risk of smoking and the presence of the new policy was not associated with decreased risk of smoking, unless there were clear rules in place (I). For the grade 10 study, (II) schools with both policies and programs were not associated with decreased risk of smoking. However, the smoking behaviour of older students (grade 12) at a school was associated with younger students’ (grade 10) smoking behaviour. Students first enrolled in a high school in grade 9, rather than grade 10, were at increased risk of occasional smoking. For students who transitioned from grade 10 to 12 (III), close friends smoking had a substantial influence on smoking behaviour for both males and females (III). Having one or more close friends who smoke (Odds Ratio (OR) = 37.46; 95% CI = 19.39 to 72.36), one or more smokers in the home (OR = 2.35; 95% CI = 1.67 to 3.30) and seeing teachers and staff smoking on or near school property (OR=1.78; 95% CI = 1.13 to 2.80), were strongly associated with increased risk of smoking for grade 12 students. Smoking behaviour increased for both junior (Group 1) and senior (Group 2) students (IV). Group 1 students indicated a greater decrease in smoking behaviour and factors influencing smoking behaviour compared to those of Group 2. Students overestimating the percentage of youth their age who smoke was strongly associated with increased likelihood of smoking. Smoking rates showed a decreasing trend (1999, 2000, and 2001). However, policies and programs alone were not successful in influencing smoking behaviour of youth. Rather, factors within the students and schools contextual environment influenced smoking behaviour. Comprehensive approaches are required for school-based tobacco prevention interventions. Keywords: schools, policy, programs, smoking prevention, adolescents Subject Terms: school-based programming, public health, health promotion

A novel fibre-coated sorbent for rapid removal of heavy metals from wastewater. Sorption of Zinc(II) from dilute aqueous solutions in the presence of high concentrations of common salts

The commercial acrylic fibre "Cashmilon" was partially hydrolyzed to convert a fraction of its nitrile (-CN) groups to carboxylic acid (-COOH) groups and then coated with polyethylenimine (PEI) resin and cross-linked with glutaraldehyde to produce a novel gel-coated fibrous sorbent with multiple functionalities of cationic, anionic and chelating types, and significantly faster sorption kinetics than bead-form sorbents. The sorption properties of the fibrous sorbent were measured using Zn(II) in aqueous solution as the sorbate to determine the effects of pH and the presence of common ions in the solution on the sorption capacity. The rate of sorption on the gel-coated fibre was measured in comparison with that on Amberlite IRA-68 weak-base resin beads, to demonstrate the marked difference between fibre and bead-form sorbents in their kinetic behaviour.

RACK: RApid Clustering using K-means algorithm

The k-means algorithm is an extremely popular technique for clustering data. One of the major limitations of the k-means is that the time to cluster a given dataset D is linear in the number of clusters, k. In this paper, we employ height balanced trees to address this issue. Specifically, we make two major contributions, (a) we propose an algorithm, RACK (acronym for RApid Clustering using k-means), which takes time favorably comparable with the fastest known existing techniques, and (b) we prove an expected bound on the quality of clustering achieved using RACK. Our experimental results on large datasets strongly suggest that RACK is competitive with the k-means algorithm in terms of quality of clustering, while taking significantly less time.

A new approach for simple and rapid shape measurement of objects with surface discontinuities

A new approach for unwrapping phase maps, obtained during the measurement of 3-D surfaces using sinusoidal structured light projection technique, is proposed. "Takeda's method" is used to obtain the wrapped phase map. Proposed method of unwrapping makes use of an additional image of the object captured under the illumination of a specifically designed color-coded pattern. The new approach demonstrates, for the first time, a method of producing reliable unwrapping of objects even with surface discontinuities from a single-phase map. It is shown to be significantly faster and reliable than temporal phase unwrapping procedure that uses a complete exponential sequence. For example, if a measurement with the accuracy obtained by interrogating the object with S fringes in the projected pattern is carried out with both the methods, new method requires only 2 frames as compared to (log(2)S +1) frames required by the later method.

A simple and rapid method for quantification of hapten specific antibodies

A sensitive and simple method for quantification of antibodies against small molecules is described using DNP-lysozyme as the enzyme conjugate. The anti-DNP antiserum was raised against DNP-bovin serum albumin conjugate. Anti-DNP antibody or its monovalent fragment (Fab) reduced the enzyme activity of DNP-lysozyme conjugate in a concentration-dependent manner. The inhibition of enzyme activity is a specific measure of the antibody and Fab content of the sample. The specificity of the reaction was assessed by reduction of antibody-induced inhibition by DNP-lysine. The ability of DNP-lysine to reduce the antibody-induced inhibition of DNP-lysozyme activity also makes possible a sensitive assay for DNP-lysine.

A novel fibre-coated sorbent for rapid removal of heavy metals from wastewater. Sorption of Zinc(II) from dilute aqueous solutions in the presence of high concentrations of common salts

The commercial acrylic fibre "Cashmilon" was partially hydrolyzed to convert a fraction of its nitrile (-CN) groups to carboxylic acid (-COOH) groups and then coated with polyethylenimine (PEI) resin and cross-linked with glutaraldehyde to produce a novel gel-coated fibrous sorbent with multiple functionalities of cationic, anionic and chelating types, and significantly faster sorption kinetics than bead-form sorbents. The sorption properties of the fibrous sorbent were measured using Zn(II) in aqueous solution as the sorbate to determine the effects of pH and the presence of common ions in the solution on the sorption capacity. The rate of sorption on the gel-coated fibre was measured in comparison with that on Amberlite IRA-68 weak-base resin beads, to demonstrate the marked difference between fibre and bead-form sorbents in their kinetic behaviour.

Vitamin E may affect the life expectancy of men, depending on dietary vitamin C intake and smoking

Background: Antioxidants might protect against oxidative stress, which has been suggested as a cause of aging. Methods: The ATBC Study recruited males aged 50-69 years who smoked at least 5 cigarettes per day at the baseline. The current study was restricted to participants who were followed up past the age of 65. Deaths were identified in the National Death Registry (1445 deaths). We constructed Kaplan-Meier survival curves for all participants, and for four subgroups defined by dietary vitamin C intake and level of smoking. We also constructed Cox regression models allowing a different vitamin E effect for low and high age ranges. Results: Among all 10,837 participants, vitamin E had no effect on those who were 65 to 70 years old, but reduced mortality by 24% when participants were 71 or older. Among 2284 men with dietary vitamin C intakes above the median who smoked less than a pack of cigarettes per day, vitamin E extended life-span by two years at the upper limit of the follow-up age span. In this subgroup, the survival curves of vitamin E and no-vitamin E participants diverged at 71 years. In the other three subgroups covering 80% of the participants, vitamin E did not affect mortality. Conclusions: This is the first study to strongly indicate that protection against oxidative stress can increase the life expectancy of some initially healthy population groups. Nevertheless, the lack of effect in 80% of this male cohort shows that vitamin E is no panacea for extending life expectancy.

Rapid growth of nanotubes and nanorods of wurtzite ZnO through microwave-irradiation of a metalorganic complex of zinc and a surfactant in solution

Large quantities of single-crystalline ZnO nanorods and nanotubes have been prepared by the microwave, irradiation of a metalorganic complex of zinc, in the presence of a surfactant. The method is simple, fast, and inexpensive (as it uses a domestic microwave oven), and yields pure nanostructures of the hexagonal wurtzite phase of ZnO in min, and requires no conventional templating. The ZnO nanotubes formed have a hollow core with inner diameter varying from 140-160 nm and a wall of thickness, 40-50 nm. The length of nanorods and nanotubes varies in the narrow range of 500-600 nm. These nanostructures have been characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and selected area electron diffraction (SAED). The ZnO nanorods and nanotubes are found by SAED to be single-crystalline. The growth process of ZnO nanorods and nanotubes has been investigated by varying the surfactant concentration and microwave irradiation time. Based on the various results obtained, a tentative and plausible mechanism for the formation of ZnO nanostructures is proposed.

New phase unwrapping strategy for rapid and dense 3D data acquisition in structured light approach

Sinusoidal structured light projection (SSLP) technique, specifically-phase stepping method, is in widespread use to obtain accurate, dense 3-D data. But, if the object under investigation possesses surface discontinuities, phase unwrapping (an intermediate step in SSLP) stage mandatorily require several additional images, of the object with projected fringes (of different spatial frequencies), as input to generate a reliable 3D shape. On the other hand, Color-coded structured light projection (CSLP) technique is known to require a single image as in put, but generates sparse 3D data. Thus we propose the use of CSLP in conjunction with SSLP to obtain dense 3D data with minimum number of images as input. This approach is shown to be significantly faster and reliable than temporal phase unwrapping procedure that uses a complete exponential sequence. For example, if a measurement with the accuracy obtained by interrogating the object with 32 fringes in the projected pattern is carried out with both the methods, new strategy proposed requires only 5 frames as compared to 24 frames required by the later method.