intellectual vanities… about close to everything

Posts Tagged ‘smoking

How Smoking Encourages Infection

with 2 comments

Smokers are often more prone to bacterial infections and inflammatory diseases than the rest of us, thanks to hundreds of toxic components in their cigarettes. Next to dry and irritated mucosal linings in mouth and respiratory system due to smoke and nicotine, now new research shows that nicotine affects neutrophils, the short-lived white blood cells that defend against infection, by reducing their ability to seek and destroy bacteria.

Neutrophils are generated by our bone marrow, which they leave as terminally differentiated cells. Although nicotine is known to affect neutrophils, there has been no study until now of the mechanisms at work when nicotine is present during neutrophil differentiation. David Scott from the Oral Health and Systemic Disease Research Group at the University of Louisville School of Dentistry, Kentucky, USA, along with a team of international colleagues decided to investigate how nicotine influenced the differentiation process.

The authors suggest the processes they observed as contributing to impaired neutrophil function partially explain chronic tobacco users’ increased susceptibility to bacterial infection and inflammatory diseases. A better understanding of this relationship could pave the way for specific therapeutic strategies to treat a number of important tobacco-associated inflammatory diseases and conditions.

The team modeled the neutrophil differentiation process beginning with promyelocytic HL-60 cells, which differentiated into neutrophils following dimethylsulfoxide (DMSO) treatment both with and without nicotine. The researchers found that nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone, but did not affect other neutrophil differentiation markers that they examined.

However, the nicotine treated neutrophils were less able to seek and destroy bacteria than nicotine-free neutrophils. The nicotine suppressed the oxidative burst in HL-60 cells, a function that helps kill invading bacteria. Nicotine also increased MMP-9 release, a factor involved in tissue degradation.

BMC Cell Biol. 2008 Apr 15;9(1):19 [Epub ahead of print]
The influence of nicotine on granulocytic differentiation – inhibition of the oxidative burst and bacterial killing and increased matrix metalloproteinase-9 release.

ABSTRACT: BACKGROUND: Neutrophils leave the bone marrow as terminally differentiated cells, yet little is known of the influence of nicotine or other tobacco smoke components on neutrophil differentiation. Therefore, promyelocytic HL-60 cells were differentiated into neutrophils using dimethylsulfoxide in the presence and absence of nicotine (3-(1-methyl-2-pyrrolidinyl) pyridine). Differentiation was evaluated over 5 days by monitoring terminal differentiation markers (CD11b expression and formazan deposition); cell viability, growth phase, kinetics, and apoptosis; assessing cellular morphology and ultrastructure; and conformational changes to major cellular components. Key neutrophil effector functions (oxidative burst, bacterial killing, matrix metalloproteinase release) were also examined. Results: Nicotine increased the percentage of cells in late differentiation phases (metamyelocytes, banded neutrophils and segmented neutrophils) compared to DMSO alone (p < 0.05), but did not affect any other marker of neutrophil differentiation examined. However, nicotine exposure during differentiation suppressed the oxidative burst in HL-60 cells (p < 0.001); inhibited bacterial killing (p < 0.01); and increased the LPS-induced release of MMP-9, but not MMP-2 (p < 0.05). These phenomena may be alpha-7-acetylcholine nicotinic receptor-dependent. Furthermore, smokers exhibited an increased MMP-9 burden compared to non-smokers in vivo (p < 0.05). Conclusions: These findings may partially explain the known increase in susceptibility to bacterial infection and neutrophil-associated destructive inflammatory diseases in individuals chronically exposed to nicotine.


Written by huehueteotl

April 18, 2008 at 8:56 am

Smoking And Heroine Have Surprisingly Similar Affect On Brain’s Reward System

leave a comment »

“That was good!” “Do it again.” This is what the rat brain says when researchers use nicotine, as well as ‘hard drugs’ such as heroin with it in the laboratory. New research indicates that the effects of nicotine and opiates on the brain’s reward system are equally strong in a key pleasure-sensing areas of the brain — the nucleus accumbens.“Testing rat brain tissue, we found remarkable overlap between the effects of nicotine and opiates on dopamine signaling within the brain’s reward centers,” says Daniel McGehee, Associate Professor in Anesthesia & Critical Care at the University of Chicago Medical Center.

McGehee and colleagues are exploring the control of dopamine, a key neurotransmitter in reward and addiction. Dopamine is released in areas such as the nucleus accumbens by naturally rewarding experiences such as food, sex, some drugs, and the neutral stimuli or ‘cues’ that become associated with them.

Nicotine and opiates are very different drugs, but the endpoint, with respect to the control of dopamine signaling, is almost identical. “There is a specific part of the nucleus accumbens where opiates have been shown to affect behavior, and when we tested nicotine in that area, the effects on dopamine are almost identical,” says McGehee.

This research is important to scientists because it demonstrates overlap in the way the two drugs work, complementing previous studies that showed overlapping effects on physiology of the ventral tegmenal area, another key part of the brain’s reward circuitry. The hope is that this study will help identify new methods for treating addiction — and not just for one drug type.

“It also demonstrates the seriousness of tobacco addiction, equating its grip on the individual to that of heroin. It reinforces the fact that these addictions are very physiological in nature and that breaking away from the habit is certainly more than just mind over matter,” says McGehee. This is certainly a preposterous conclusion from rat brain experiments. Clinical evidence with humans proves at least, that quitting cigarettes is ways more often successful than quitting heroin.

J Neurosci. 2008 Feb 13;28(7):1672-81.
Presynaptic opioid and nicotinic receptor modulation of dopamine overflow in the nucleus accumbens.

Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.

Behaviorally relevant stimuli prompt midbrain dopamine (DA) neurons to switch from tonic to burst firing patterns. Similar shifts to burst activity are thought to contribute to the addictive effects of opiates and nicotine. The nucleus accumbens DA overflow produced by these drugs is a key element in their pathological effects. Using electrochemical techniques in brain slices, we explored the effects of opioids on single-spike and burst stimuli-evoked DA overflow in the dorsal and ventral striatum. In specific subregions of the nucleus accumbens, mu-opioids inhibit DA overflow elicited with single-spike stimuli while leaving that produced by burst stimuli unaffected. This is similar to published effects of nicotinic receptor blockade or desensitization, and is mediated by opioid receptor-induced inhibition of cholinergic interneurons. Whereas delta-opioids have similar effects, kappa-opioids inhibit evoked DA overflow throughout the striatum in a manner that is not overcome with high-frequency stimuli. These observations reveal remarkable mechanistic overlap between the effects of nicotine and opiates within the dopamine reward pathway.

Written by huehueteotl

February 19, 2008 at 3:51 pm

Let Us Eat And Drink; For To Morrow We Shall Die.

with 4 comments

At least Isaiah xxii. 13 (AV) has it like this. he did not know that overweight smokers are an even less financial burden for public health. They simply die soonest, causing the least cost in health care systems.

A new research paper suggests that preventing obesity might result in increased public spending on medical care. Many countries are currently developing policies aimed at reducing obesity in the population. However, it is not currently clear whether successfully reducing obesity will also reduce national healthcare spending or not. Pieter van Baal and colleagues, from the National Institute for Public Health and the Environment in the Netherlands, created a mathematical model to try to answer this question.

In their study, van Baal and his co-workers created three hypothetical populations of 1000 men and women, all aged 20 years at the start: a group of obese, never-smoking individuals; a group of healthy-never smoking individuals of normal weight; and a group of smokers of normal weight. The model produced an estimate of the likely proportion of each group who would encounter certain long term (chronic) diseases, and then estimated what the approximate cost of medical care associated with each disease was likely to be. The researchers found that the group of healthy, never-smoking individuals had the highest lifetime healthcare costs, because they lived the longest and developed diseases associated with aging; healthcare costs were lowest for the smokers, and intermediate for the group of obese never-smokers.

However, the authors argue that although obesity prevention may not be a cure for increasing expenditures, it may well be a cost-effective cure for much morbidity and mortality and importantly contribute to the health of nations.

Should Isaiah’s biblical ammendment be then. “Eat, drink, smoke and be merry, for tomorrow we diet”? Mind, this is a mathematical model comparing life-time-health-costs. Main target of medicine is not keeping public health cheap but people healthy until old age! A Perspective by Klim McPherson, from Oxford University in the UK, who was not involved in the study, discusses the implications of these findings and comments that “it would be wrong to interpret the findings as meaning that public-health prevention (e.g., to prevent obesity) has no benefits”; the quality of life experienced by individuals, and other factors, must also be taken into account when planning interventions aimed at improving public health.

van Baal PHM, Polder JJ, de Wit GA, Hoogenveen RT, Feenstra TL, et al. (2008)

Lifetime medical costs of obesity: Prevention no cure for increasing health expenditure.

PLoS Med 5(2): e29. doi:10.1371/journal.pmed.0050029

BackgroundObesity is a major cause of morbidity and mortality and is associated with high medical expenditures. It has been suggested that obesity prevention could result in cost savings. The objective of this study was to estimate the annual and lifetime medical costs attributable to obesity, to compare those to similar costs attributable to smoking, and to discuss the implications for prevention.

Methods and Findings

With a simulation model, lifetime health-care costs were estimated for a cohort of obese people aged 20 y at baseline. To assess the impact of obesity, comparisons were made with similar cohorts of smokers and “healthy-living” persons (defined as nonsmokers with a body mass index between 18.5 and 25). Except for relative risk values, all input parameters of the simulation model were based on data from The Netherlands. In sensitivity analyses the effects of epidemiologic parameters and cost definitions were assessed. Until age 56 y, annual health expenditure was highest for obese people. At older ages, smokers incurred higher costs. Because of differences in life expectancy, however, lifetime health expenditure was highest among healthy-living people and lowest for smokers. Obese individuals held an intermediate position. Alternative values of epidemiologic parameters and cost definitions did not alter these conclusions.


Although effective obesity prevention leads to a decrease in costs of obesity-related diseases, this decrease is offset by cost increases due to diseases unrelated to obesity in life-years gained. Obesity prevention may be an important and cost-effective way of improving public health, but it is not a cure for increasing health expenditures.

Written by huehueteotl

February 7, 2008 at 4:23 pm

Genes Predict Risk Of Getting Hooked On Cigarettes

with one comment

Cigarette smoking is the largest preventable source of death and disability in the USA, contributing to ~ 400,000 deaths annually. Despite widespread knowledge of the health dangers, ~ 1 in 8 American adults is a habitual heavy smoker.
For several decades, scientists have known that most of the risk for habitual heavy smoking (smoking a pack each day) is largely influenced by genetics. This conclusion comes from the study of identical and fraternal twins from Scandinavia, North America, Australia and (more recently) China. It has been estimated that ~ 2/3 of the risk to become a heavy habitual smoker is genetic. This does not imply that this genetic risk is due to a single gene. It is known that many genes are involved, each one contributing a small amount of risk.

Finding the individual genes is a considerable challenge, but worth the effort, because it is hoped that the genes conveying risk for heavy smoking could be used to develop new medicines to help people quit. The development of new medicines to help people quit is particularly important, because the existing medications, including nicotine replacement (‘the patch’ or gum), bupropion and varenicline are effective in the short-term (several months) for a minority of heavy smokers.

This paper describes the results of a genetic study of 14,000 people, from the USA and Europe, whose smoking histories were known. DNA samples from ~ 6000 people were analyzed at ~ 500,000 known variations in the human genome to determine whether any of these variations predicted cigarettes per day during the period of heaviest smoking for these individuals. The results implicated variations in two genes, both producing brain proteins to which nicotine binds in generating its addicting effects. These two proteins (are their genes) are termed the alpha 3 and alpha 5 nicotinic receptor subunits, so-called because they form (with other nicotinic receptor subunits) binding sites for nicotine on certain brain cells which are known to be activated during the process of addiction.

A second population of ~ 8000 people (whose smoking histories were known) was analyzed in a similar manner, the result again suggesting that variations in these two genes increased risk for heavy smoking. Taken together, these two studies provide convincing proof that variations in the alpha 3 and alpha 5 nicotinic receptor subunit genes play a significant role in risk for nicotine addiction. A previously published paper, using similar methods, also supports this conclusion.

These results suggest two important research activities. First, and foremost, the alpha 3 and alpha 5 nicotinic receptor subunits will be made targets for new smoking cessation medication development programs by pharmaceutical companies. Second, the implicated DNA variants can be used to determine whether they predict ability to quit using the one of the currently available smoking cessation medicines. This “personalized medicine” approach might allow for more efficient and productive use of those medicines, until improved ones can be created.

Mol Psychiatry. 2008 Jan 29 [Epub ahead of print]
alpha-5/alpha-3 nicotinic receptor subunit alleles increase risk for heavy smoking.
[1] 1Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA [2] 2Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Upper Merion, PA, USA [3] 3Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Verona, Italy.

Twin studies indicate that additive genetic effects explain most of the variance in nicotine dependence (ND), a construct emphasizing habitual heavy smoking despite adverse consequences, tolerance and withdrawal. To detect ND alleles, we assessed cigarettes per day (CPD) regularly smoked, in two European populations via whole genome association techniques. In these approximately 7500 persons, a common haplotype in the CHRNA3-CHRNA5 nicotinic receptor subunit gene cluster was associated with CPD (nominal P=6.9 x 10(-5)). In a third set of European populations (n= approximately 7500) which had been genotyped for approximately 6000 SNPs in approximately 2000 genes, an allele in the same haplotype was associated with CPD (nominal P=2.6 x 10(-6)). These results (in three independent populations of European origin, totaling approximately 15 000 individuals) suggest that a common haplotype in the CHRNA5/CHRNA3 gene cluster on chromosome 15 contains alleles, which predispose to ND.Molecular Psychiatry advance online publication, 29 January 2008; doi:10.1038/

see also:

smoking is a thing in the head – nicotine rush too

The Brain And The Nicotine


Written by huehueteotl

January 31, 2008 at 4:33 pm

Giving Up Marijuana Feels As Bad As Giving Up Cigarettes

with 34 comments

Research by a group of scientists studying the effects of heavy marijuana use suggests that withdrawal from the use of marijuana is similar to what is experienced by people when they quit smoking cigarettes: bad feeling, but no real withdrawal. Abstinence from each of these drugs appears to cause several common symptoms, such as irritability, anger and trouble sleeping – based on self reporting in a recent study of 12 (!) heavy users of both marijuana and cigarettes. The authors recognize that the small sample size is a limitation in this study, but the results are consistent with other studies indicating that marijuana withdrawal effects are clinically important. And, they are not surprising, given that any forced change of habits does lead to similar complaints.

“These results indicate that some marijuana users experience withdrawal effects when they try to quit, and that these effects should be considered by clinicians treating people with problems related to heavy marijuana use,” says lead investigator in the study, Ryan Vandrey, Ph.D., of the Department of Psychiatry at the Johns Hopkins University School of Medicine.

Marijuana is the most widely used illicit drug in the United States. Admissions in substance abuse treatment facilities in which marijuana was the primary problem substance have more than doubled since the early 1990s and now rank similar to cocaine and heroin with respect to total number of yearly treatment episodes in the United States, says Vandrey.

He points out that a lack of data, until recently, has led to cannabis withdrawal symptoms not being characterized or included in medical reference literature such as the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, (DSM-IV) or the International Classification of Diseases, 10th edition (ICD-10).

Since the drafting of the DSM-IV in 1994, an increasing number of studies have surfaced suggesting that cannabis has significant withdrawal symptoms. What makes Vandrey’s recent study unique is that it is the first study that compares marijuana withdrawal symptoms to withdrawal symptoms that are clinically recognized by the medical community – specifically the tobacco withdrawal syndrome.

“Since tobacco withdrawal symptoms are well documented and included in the DSM-IV and the IDC-10, we can infer from the results of this comparison that marijuana withdrawal is also clinically significant and should be included in these reference materials and considered as a target for improving treatment outcomes,” says Vandrey.

Vandrey added that this is the first “controlled” comparison of the two withdrawal syndromes in that data was obtained using rigorous scientific methods – abstinence from drugs was confirmed objectively, procedures were identical during each abstinence period, and abstinence periods occurred in a random order. That tobacco and marijuana withdrawal symptoms were reported by the same participants, thus eliminating the likelihood that results reflect physiological differences between subjects, is also a strength of the study.

Interestingly, the study also revealed that half of the participants found it easier to abstain from both substances than it was to stop marijuana or tobacco individually, whereas the remaining half had the opposite response.

“Given the general consensus among clinicians that it is harder to quit more than one substance at the same time, these results suggest the need for more research on treatment planning for people who concurrently use more than one drug on a regular basis,” says Vandrey.

Vandrey’s study, which appears in the January issue of the journal Drug and Alcohol Dependence, followed six men and six women at the University of Vermont in Burlington and Wake Forest University School of Medicine in Winston-Salem, N.C., for a total of six weeks. All were over 18 (median age 28.2 years), used marijuana at least 25 days a month and smoked at least 10 cigarettes a day. None of the subjects intended to quit using either substance, did not use any other illicit drugs in the prior month, were not on any psychotropic medication, did not have a psychiatric disorder, and if female, were not pregnant.

For the first week, participants maintained their normal use of cigarettes and marijuana. For the remaining five weeks, they were randomly chosen to refrain from using either cigarettes, marijuana or both substances for five-day periods separated by nine-day periods of normal use. In order to confirm abstinence, patients were given daily quantitative urine toxicology tests of tobacco and marijuana metabolites.

Withdrawal symptoms were self reported on a daily basis Monday through Friday using a withdrawal symptom checklist that listed scores for aggression, anger, appetite change, depressed mood, irritability, anxiety/nervousness, restlessness, sleep difficulty, strange dreams and other, less common withdrawal symptoms. Patients also provided an overall score for discomfort they experienced during each abstinence period.

Results showed that overall withdrawal severity associated with marijuana alone and tobacco alone was of similar frequency and intensity. Sleep disturbance seemed to be more pronounced during marijuana abstinence, while some of the general mood effects (anxiety, anger) seemed to be greater during tobacco abstinence. In addition, six of the participants reported that quitting both marijuana and tobacco at the same time was more difficult than quitting either drug alone, whereas the remaining six found that it was easier to quit marijuana or cigarettes individually than it was to abstain from the two substances simultaneously.

Drug Alcohol Depend. 2008 Jan 1;92(1-3):48-54. Epub 2007 Jul 23.

A within-subject comparison of withdrawal symptoms during abstinence from cannabis, tobacco, and both substances.

Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

A cannabis withdrawal syndrome has been characterized, but its clinical significance remains uncertain. One method of assessing the significance of cannabis withdrawal is to compare it directly to an established withdrawal syndrome. The present study was a within-subject comparison of cannabis, tobacco, and combined cannabis and tobacco withdrawal among users of both substances. Participants (N=12) completed three 5-day periods of abstinence in a randomized order, separated by 9-day periods of usual substance use. Overall withdrawal severity associated with cannabis alone and tobacco alone was of a similar magnitude. Withdrawal during simultaneous cessation of both substances was more severe than for each substance alone, but these differences were of short duration and substantial individual differences were noted. These results are consistent with other evidence suggesting cannabis withdrawal is clinically important and warrants detailed description in the DSM-V and ICD-11. Additional research is needed to replicate these findings and to further investigate the effects of abstaining from multiple drugs simultaneously

Written by huehueteotl

January 25, 2008 at 4:13 pm