Friday 30 November 2012
Electronic Cigarette - Ecigs - Information on News
An electronic cigarette (e-cigarette) is a battery - powered device that provides inhaled doses of nicotine by way of a vaporized solution. It is a healthier alternative to smoked tobacco products, such as cigarettes, cigars, or pipes. Nicocure eCigs is a leader in developing high quality, technologically advanced products in this field.
Monday 26 November 2012
Electronic Cigarette - Frequent Asked Question About Nicocure Ecigs
Nicocure Electronic Cigarette – Smoke Without Worrying About It
While smoking cigarettes (another modern term - analog cigarettes) is primarily a social thing, the fact remains that many people do it because they actually enjoy it; the addiction to nicotine is simply a by-product of the activity.
Unfortunately, the cigarettes we are being sold today are filled with thousands of toxic chemicals, and as I’m sure you know, there is a clear statistical correlation between the number of smokers on the planet and the number of lung cancer cases.
Long story short, smoking is obviously bad for you, but it’s a habit many of us aren’t willing to even try breaking just yet. Back in the 1970s some research was already done about electronic cigarettes, but the technology wasn’t advanced enough to really make them work. Fortunately, in 2006 a Chinese company restarted the research and development on the electronic cigarette, and today there are hundreds of brands to choose from.
While smoking cigarettes (another modern term - analog cigarettes) is primarily a social thing, the fact remains that many people do it because they actually enjoy it; the addiction to nicotine is simply a by-product of the activity.
Unfortunately, the cigarettes we are being sold today are filled with thousands of toxic chemicals, and as I’m sure you know, there is a clear statistical correlation between the number of smokers on the planet and the number of lung cancer cases.
Long story short, smoking is obviously bad for you, but it’s a habit many of us aren’t willing to even try breaking just yet. Back in the 1970s some research was already done about electronic cigarettes, but the technology wasn’t advanced enough to really make them work. Fortunately, in 2006 a Chinese company restarted the research and development on the electronic cigarette, and today there are hundreds of brands to choose from.
Are Electronic Cigarettes Safe?
Before talking about the e-cigs themselves, I’d like to answer a question many people have on the tip of their tongue: are electronic cigarettes safe? Well, ever since people have started buying them, there has been one case of an electronic cigarette blowing up in someone’s, knocking out eight of the guy’s teeth. HOWEVER, the guy admitted that he made some personal modification to his model because he wanted to get more vapor when inhaling. In other words, he’s the blacksmith of his own misfortune.
Apart from that, not a single case of e-cigs harming anybody has been noted.It should also be mentioned that electronic cigarettes could very well put tobacco companies out of business relatively soon, which is why many of them are claiming e-cigs to be unsafe… which is exactly what you would expect them to do. The more electronic cigarettes will become popular, the harder tobacco companies will be fighting against them. In any case, let’s go onward with the program.
Nicocure Electronic Cigarette
One of the most popular brands of electronic cigarette is Nicocure. For those who aren’t familiar with electronic cigarettes yet, they have a starter kit available, and it’s actually one of the best ones on the market. As far as looks and taste are concerned, rest assured that they look exactly like the real thing, and the tobacco flavor is still as strong as it ever was.
To answer the question many are probably asking, yes you do feel the pleasurable sensation of having smoke go down your lungs, except for a few differences. For starters, you are only going to be smoking a mix of water, nicotine, and in most cases propylene glycol. That’s it. As you can guess, it’s infinitely healthier than regular cigarettes, not to mention that you can actually smoke them anywhere as you’ll only be exhaling water vapor.
Also, it has to be mentioned to e-cigs last much longer than regular ones, and you’ll be saving hundreds, perhaps even a thousand or two on a yearly basis. To reiterate, electronic cigarettes don’t have toxic chemicals, tar, they don’t give you yellow teeth, ad breath, smelly clothes or a smoker’s cough, and you can smoke them virtually anywhere.
The Nicocure Electronic Cigarette Starter Kit
While most companies simply include the e-cigarettes and a solid case with their starter kit, Nicocure provides you with 5 flavored tobacco cartomizers, rechargeable lithium batteries, a USB charger, a solid storage case, a wall charger, not to mention that it comes with a lifetime warranty should anything happen.
To learn more about Nicocure and electronic cigarettes or place your order, simply head on over to the link below.
credit to : health-avenue.blogspot.com
Tuesday 13 November 2012
What is an Electronic Cigarette? The Best eCigs Review
An electronic cigarette (e-cigarette) is a battery - powered device that provides inhaled doses of nicotine by way of a vaporized solution. It is a healthier alternative to smoked tobacco products, such as cigarettes, cigars, or pipes. Nicocure eCigs is a leader in developing high quality, technologically advanced products in this field.
An electronic cigarette, also known as an e-cigarette, is an electrical device that simulates the act of tobacco smoking by producing an inhaled vapor bearing the physical sensation, appearance, and often the flavor (with or without nicotine content) of inhaled tobacco smoke, without its odor or, ostensibly, its health risks. The device uses heat (or in some cases, ultrasonics) to vaporize a propylene glycol- or glycerin-based liquid solution into an aerosol mist, similar to the way a nebulizer or humidifier vaporizes solutions for inhalation.
The device's components usually include a small liquid reservoir, a heating element, and a power source, which may be a battery or a wired USB adapter. Most electronic cigarettes are portable, self-contained cylindrical devices in varying sizes, and many are designed to outwardly resemble traditional cigarettes. Most are also reusable, with replaceable and refillable components, though some models are disposable. Liquids that produce vapor for electronic cigarettes are available in many different flavor varieties and nicotine concentrations, including nicotine-free versions.
An electronic cigarette, also known as an e-cigarette, is an electrical device that simulates the act of tobacco smoking by producing an inhaled vapor bearing the physical sensation, appearance, and often the flavor (with or without nicotine content) of inhaled tobacco smoke, without its odor or, ostensibly, its health risks. The device uses heat (or in some cases, ultrasonics) to vaporize a propylene glycol- or glycerin-based liquid solution into an aerosol mist, similar to the way a nebulizer or humidifier vaporizes solutions for inhalation.
The device's components usually include a small liquid reservoir, a heating element, and a power source, which may be a battery or a wired USB adapter. Most electronic cigarettes are portable, self-contained cylindrical devices in varying sizes, and many are designed to outwardly resemble traditional cigarettes. Most are also reusable, with replaceable and refillable components, though some models are disposable. Liquids that produce vapor for electronic cigarettes are available in many different flavor varieties and nicotine concentrations, including nicotine-free versions.
The primary stated use of the electronic cigarette is as an alternative to tobacco smoking, or as a smoking cessation device: It endeavors to deliver the experience of smoking without the adverse health effects associated with tobacco smoke, or at least to greatly reduce those risks.
The possible benefits or adverse effects of electronic cigarette use are a subject of uncertainty among all health organizations and researchers. Controlled studies of electronic cigarettes are scarce due to their relatively recent invention and subsequent rapid growth in popularity. Laws governing the use and sale of electronic cigarettes, as well as the accompanying liquid solutions, currently vary widely, with pending legislation and ongoing debate in many regions. Concerns have been raised by anti-smoking groups that use of the device still might carry health risks and that it could appeal to non-smokers, especially children, due to its novelty, flavorings, and possibly overstated claims of safety.
In 2000, Chinese pharmacist Hon Lik invented a new version of the electronic cigarette that used a piezoelectric ultrasound-emitting element to vaporize a pressurized jet of liquid containing nicotine diluted in a propylene glycol solution. This design produced a smoke-like vapor that could be inhaled and provided an effective vehicle for nicotine delivery into the bloodstream via the lungs. There was little interest in this design until 2004, when it was first introduced to the Chinese domestic market. The company he worked for, Golden Dragon Holdings, changed its name to Ruyan (meaning "to resemble smoking"), and started exporting its products in 2005–2006, before receiving the first international patent in 2007.
While Hon Lik is widely credited with the invention of the electronic cigarette (he has claimed the idea appeared to him in a dream), the modern form of the device is more similar to Gilbert's original design. In fact, vaporizers for the purpose of inhaling substances have been commercially available for several years although these are designed to vaporise solid plant material and possibly more popular for inhaling cannabis rather than tobacco. Perhaps reflecting his expertise as a chemist, Hon Lik's main innovation appears to be restricted to the use of nicotine in a free base form (pharmaceutical-grade nicotine) diluted with propylene glycol, a mixture now widely used in modern electronic cigarettes.
While Hon Lik is widely credited with the invention of the electronic cigarette (he has claimed the idea appeared to him in a dream), the modern form of the device is more similar to Gilbert's original design. In fact, vaporizers for the purpose of inhaling substances have been commercially available for several years although these are designed to vaporise solid plant material and possibly more popular for inhaling cannabis rather than tobacco. Perhaps reflecting his expertise as a chemist, Hon Lik's main innovation appears to be restricted to the use of nicotine in a free base form (pharmaceutical-grade nicotine) diluted with propylene glycol, a mixture now widely used in modern electronic cigarettes.
Nicotine Addiction
Nicotine addiction is the second-leading cause of death worldwide. The important causes of smoking-related mortality are atherosclerotic vascular disease, cancer, and chronic obstructive pulmonary disease (COPD). Smoking also can contribute to other diseases, such as histiocytosis X, respiratory bronchiolitis, obstructive sleep apnea, idiopathic pneumothorax, low birth weight, and perinatal mortality.
Currently, there are about 1.3 billion smokers the world, most (84%) of them in developing countries.[1] If current smoking trends continue, tobacco will kill 10 million people each year by 2020. Through direct healthcare costs and loss of productivity from death and illness, tobacco will cost governments an estimated US $200 billion per year. A third of these costs will be borne by the developing countries. Many factors have led to increased global smoking rates, including the following:
Trade liberalization
Direct foreign investment
Global marketing
Transnational tobacco advertising, promotion, and sponsorship
International tobacco smuggling
Research investigating why people smoke has shown that smoking behavior is multifaceted. Factors influencing initiation of smoking differ from those influencing maintenance of smoking behavior. Nicotine dependence, genetic factors, and psychosocial factors all influence maintenance of smoking behavior.
Nicotine in cigarette smoke affects mood and performance and is the source of addiction to tobacco. It meets the criteria of a highly addictive drug, in that it is a potent psychoactive substance that induces euphoria, reinforces its own use, and leads to nicotine withdrawal syndrome when it is absent. As an addictive drug, nicotine has 2 very potent effects, being both a stimulant and a depressant. Thus, cigarettes may both get a smoker going in the morning and “chill out” the smoker during the day.
All healthcare professionals should be aware of the risks of tobacco smoking, understand nicotine addiction, and assist patients with smoking cessation.
In their 2010 guidelines, the American Heart Association (AHA) and the American Stroke Association (ASA) strongly recommended that smokers consider smoking cessation because of the direct correlation between smoking and both ischemic stroke and subarachnoid hemorrhage. Clinicians should provide counseling, nicotine replacement, and oral smoking cessation medications as options. Avoiding exposure to environmental tobacco smoke is reasonable.
Illustrative case study
A young adult man met his primary care physician for the first time, during which his prior military history came to light. The young man recalled the anxiety he experienced when he received his military orders for deployment to Iraq. Before being notified of deployment, he smoked cigarettes only occasionally, perhaps 1 or 2 cigarettes a day.
As the time for deployment approached, the young man started smoking more cigarettes, and by the time he arrived in Iraq, he was up to a full pack a day. Throughout the 12-month deployment, the soldier steadily increased his smoking, reaching a peak consumption of nearly 40 cigarettes a day. He sustained several significant combat-related traumas resulting in mild physical injuries.
After returning home, the young man completed his military obligation and left the service. Although experiencing some lingering physical and emotional pain from his tour of duty, he was improving, except in 1 area: He continued to smoke 2 packs a day, despite efforts to quit. The former soldier’s wife complained that the expensive habit was creating an unnecessary financial strain on their meager resources. Furthermore, the young man himself no longer derived much pleasure from smoking, admitting that only the first cigarette of the day was truly enjoyable.
Despite his apparent willingness to consider quitting the use of tobacco, the former soldier also readily admitted that he was frightened by the prospect. He recognized that his unresolved emotional issues from the war, though currently being addressed in treatment, gave him a reason not to tackle another problem at this time. The doctor appreciated the frank disclosure but took issue with the patient’s conclusion. The patient appeared motivated and open to change but needed additional encouragement to consider a smoking cessation program.
At this point, the doctor decided to discuss concomitant disorders by explaining the common association of a mental disorder with substance misuse. The doctor further explained how tobacco use, at least in the beginning, helped the former soldier cope with anxiety. Trauma suffered in the war led to the developed of posttraumatic stress disorder (PTSD). The continued use of tobacco made it difficult to distinguish the symptoms of nicotine dependence from those of PTSD and delayed recovery from the emotional disorder.
The doctor asked the patient to think about this information and consider a smoking cessation program. Various medications were described that could alleviate nicotine withdrawal symptoms or reduce tobacco cravings. Such medications, combined with a behavioral strategy, offered the safest and surest route to a tobacco-free life. Discussions continued over a few more visits (including a meeting with the wife) before the patient decided to give up smoking. With the doctor’s help, he successfully completed a 3-month smoking cessation program.
credit : medscape.com
Currently, there are about 1.3 billion smokers the world, most (84%) of them in developing countries.[1] If current smoking trends continue, tobacco will kill 10 million people each year by 2020. Through direct healthcare costs and loss of productivity from death and illness, tobacco will cost governments an estimated US $200 billion per year. A third of these costs will be borne by the developing countries. Many factors have led to increased global smoking rates, including the following:
Trade liberalization
Direct foreign investment
Global marketing
Transnational tobacco advertising, promotion, and sponsorship
International tobacco smuggling
Research investigating why people smoke has shown that smoking behavior is multifaceted. Factors influencing initiation of smoking differ from those influencing maintenance of smoking behavior. Nicotine dependence, genetic factors, and psychosocial factors all influence maintenance of smoking behavior.
Nicotine in cigarette smoke affects mood and performance and is the source of addiction to tobacco. It meets the criteria of a highly addictive drug, in that it is a potent psychoactive substance that induces euphoria, reinforces its own use, and leads to nicotine withdrawal syndrome when it is absent. As an addictive drug, nicotine has 2 very potent effects, being both a stimulant and a depressant. Thus, cigarettes may both get a smoker going in the morning and “chill out” the smoker during the day.
All healthcare professionals should be aware of the risks of tobacco smoking, understand nicotine addiction, and assist patients with smoking cessation.
In their 2010 guidelines, the American Heart Association (AHA) and the American Stroke Association (ASA) strongly recommended that smokers consider smoking cessation because of the direct correlation between smoking and both ischemic stroke and subarachnoid hemorrhage. Clinicians should provide counseling, nicotine replacement, and oral smoking cessation medications as options. Avoiding exposure to environmental tobacco smoke is reasonable.
Illustrative case study
A young adult man met his primary care physician for the first time, during which his prior military history came to light. The young man recalled the anxiety he experienced when he received his military orders for deployment to Iraq. Before being notified of deployment, he smoked cigarettes only occasionally, perhaps 1 or 2 cigarettes a day.
As the time for deployment approached, the young man started smoking more cigarettes, and by the time he arrived in Iraq, he was up to a full pack a day. Throughout the 12-month deployment, the soldier steadily increased his smoking, reaching a peak consumption of nearly 40 cigarettes a day. He sustained several significant combat-related traumas resulting in mild physical injuries.
After returning home, the young man completed his military obligation and left the service. Although experiencing some lingering physical and emotional pain from his tour of duty, he was improving, except in 1 area: He continued to smoke 2 packs a day, despite efforts to quit. The former soldier’s wife complained that the expensive habit was creating an unnecessary financial strain on their meager resources. Furthermore, the young man himself no longer derived much pleasure from smoking, admitting that only the first cigarette of the day was truly enjoyable.
Despite his apparent willingness to consider quitting the use of tobacco, the former soldier also readily admitted that he was frightened by the prospect. He recognized that his unresolved emotional issues from the war, though currently being addressed in treatment, gave him a reason not to tackle another problem at this time. The doctor appreciated the frank disclosure but took issue with the patient’s conclusion. The patient appeared motivated and open to change but needed additional encouragement to consider a smoking cessation program.
At this point, the doctor decided to discuss concomitant disorders by explaining the common association of a mental disorder with substance misuse. The doctor further explained how tobacco use, at least in the beginning, helped the former soldier cope with anxiety. Trauma suffered in the war led to the developed of posttraumatic stress disorder (PTSD). The continued use of tobacco made it difficult to distinguish the symptoms of nicotine dependence from those of PTSD and delayed recovery from the emotional disorder.
The doctor asked the patient to think about this information and consider a smoking cessation program. Various medications were described that could alleviate nicotine withdrawal symptoms or reduce tobacco cravings. Such medications, combined with a behavioral strategy, offered the safest and surest route to a tobacco-free life. Discussions continued over a few more visits (including a meeting with the wife) before the patient decided to give up smoking. With the doctor’s help, he successfully completed a 3-month smoking cessation program.
credit : medscape.com
Thursday 8 November 2012
Nicotine - A Brief Information For Us
Nicotine
Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) that acts as a nicotinic acetylcholine agonist and a monoamine oxidase inhibitor[citation needed]. The biosynthesis takes place in the roots and accumulation occurs in the leaves of the Solanaceae. It constitutes approximately 0.6–3.0% of the dry weight of tobacco and is present in the range of 2–7 µg/kg of various edible plants.It functions as an antiherbivore chemical; therefore, nicotine was widely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently widely used.
Nicotine is an alkaloid found in the nightshade family of plants (Solanaceae) that acts as a nicotinic acetylcholine agonist and a monoamine oxidase inhibitor[citation needed]. The biosynthesis takes place in the roots and accumulation occurs in the leaves of the Solanaceae. It constitutes approximately 0.6–3.0% of the dry weight of tobacco and is present in the range of 2–7 µg/kg of various edible plants.It functions as an antiherbivore chemical; therefore, nicotine was widely used as an insecticide in the past and nicotine analogs such as imidacloprid are currently widely used.
In low doses (an average cigarette yields about 1 mg of absorbed nicotine), the substance acts as a stimulant in mammals, while high amounts (30–60 mg) can be fatal.This stimulant effect is the main factor responsible for the dependence-forming properties of tobacco smoking. According to the American Heart Association, nicotine addiction has historically been one of the hardest addictions to break, while the pharmacological and behavioral characteristics that determine tobacco addiction are similar to those determining addiction to heroin and cocaine. The nicotine content of popular American-brand cigarettes has slowly increased over the years, and one study found that there was an average increase of 1.6% per year between the years of 1998 and 2005. This was found for all major market categories of cigarettes.
Research in 2011 has found that nicotine inhibits chromatin-modifying enzymes (class I and II histone deacetylases) which increases the ability of cocaine to cause an addiction.
History and name
Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560,and who promoted their medicinal use. The tobacco and seeds were brought to ambassador Nicot from Brazil by Luis de Gois, a Portuguese colonist in São Paulo. Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison.Its chemical empirical formula was described by Melsens in 1843,its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,and it was first synthesized by Amé Pictet and A. Rotschy in 1904.
Historical use of nicotine as an insecticide
Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide (waste from the tobacco industry) were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals.
Currently, nicotine is a permitted pesticide for organic farming because it is derived from a botanical source. Nicotine sulfate sold for use as a pesticide is labeled "DANGER," indicating that it is highly toxic.However, in 2008, the EPA received a request to cancel the registration of the last nicotine pesticide registered in the United States. This request was granted, and after 1 January 2014, this pesticide will not be available for sale.
Chemistry
Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to cause pharmacological effects.
Research in 2011 has found that nicotine inhibits chromatin-modifying enzymes (class I and II histone deacetylases) which increases the ability of cocaine to cause an addiction.
History and name
Nicotine is named after the tobacco plant Nicotiana tabacum, which in turn is named after the French ambassador in Portugal, Jean Nicot de Villemain, who sent tobacco and seeds to Paris in 1560,and who promoted their medicinal use. The tobacco and seeds were brought to ambassador Nicot from Brazil by Luis de Gois, a Portuguese colonist in São Paulo. Nicotine was first isolated from the tobacco plant in 1828 by physician Wilhelm Heinrich Posselt and chemist Karl Ludwig Reimann of Germany, who considered it a poison.Its chemical empirical formula was described by Melsens in 1843,its structure was discovered by Adolf Pinner and Richard Wolffenstein in 1893,and it was first synthesized by Amé Pictet and A. Rotschy in 1904.
Historical use of nicotine as an insecticide
Tobacco was introduced to Europe in 1559, and by the late 17th century, it was used not only for smoking but also as an insecticide. After World War II, over 2,500 tons of nicotine insecticide (waste from the tobacco industry) were used worldwide, but by the 1980s the use of nicotine insecticide had declined below 200 tons. This was due to the availability of other insecticides that are cheaper and less harmful to mammals.
Currently, nicotine is a permitted pesticide for organic farming because it is derived from a botanical source. Nicotine sulfate sold for use as a pesticide is labeled "DANGER," indicating that it is highly toxic.However, in 2008, the EPA received a request to cancel the registration of the last nicotine pesticide registered in the United States. This request was granted, and after 1 January 2014, this pesticide will not be available for sale.
Chemistry
Nicotine is a hygroscopic, oily liquid that is miscible with water in its base form. As a nitrogenous base, nicotine forms salts with acids that are usually solid and water soluble. Nicotine easily penetrates the skin. As shown by the physical data, free base nicotine will burn at a temperature below its boiling point, and its vapors will combust at 308 K (35 °C; 95 °F) in air despite a low vapor pressure. Because of this, most of the nicotine is burned when a cigarette is smoked; however, enough is inhaled to cause pharmacological effects.
Optical activity
Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [a]D = –166.4° ((-)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (–)-nicotine. (-)-nicotine is more toxic than (+)-nicotine. The salts of (+)-nicotine are usually dextrorotatory.
Biosynthesis
The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from nicotinic acid while the pyrrolidone is derived from N-methyl-?1-pyrrollidium cation.Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for nicotinic acid and the tropane pathway for N-methyl-?1-pyrrollidium cation.
The NAD pathway in the genus nicotiana begins with the oxidation of aspartic acid into a-imino succinate by aspartate oxidase (AO). This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form nicotinic acid mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce nicotinic acid via the conversion of nicotinamide by the enzyme nicotinamidase.
The N-methyl-?1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-?1-pyrrollidium cation.
The final step in the synthesis of nicotine is the coupling between N-methyl-?1-pyrrollidium cation and nicotinic acid. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of nicotinic acid into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-?1-pyrrollidium cation to form enantiomerically pure (–)-nicotine.
Pharmacology
Pharmacokinetics
As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation.The elimination half-life of nicotine in the body is around two hours.
Nicotine is optically active, having two enantiomeric forms. The naturally occurring form of nicotine is levorotatory with a specific rotation of [a]D = –166.4° ((-)-nicotine). The dextrorotatory form, (+)-nicotine is physiologically less active than (–)-nicotine. (-)-nicotine is more toxic than (+)-nicotine. The salts of (+)-nicotine are usually dextrorotatory.
Biosynthesis
The biosynthetic pathway of nicotine involves a coupling reaction between the two cyclic structures that compose nicotine. Metabolic studies show that the pyridine ring of nicotine is derived from nicotinic acid while the pyrrolidone is derived from N-methyl-?1-pyrrollidium cation.Biosynthesis of the two component structures proceeds via two independent syntheses, the NAD pathway for nicotinic acid and the tropane pathway for N-methyl-?1-pyrrollidium cation.
The NAD pathway in the genus nicotiana begins with the oxidation of aspartic acid into a-imino succinate by aspartate oxidase (AO). This is followed by a condensation with glyceraldehyde-3-phosphate and a cyclization catalyzed by quinolinate synthase (QS) to give quinolinic acid. Quinolinic acid then reacts with phosphoriboxyl pyrophosphate catalyzed by quinolinic acid phosphoribosyl transferase (QPT) to form nicotinic acid mononucleotide (NaMN). The reaction now proceeds via the NAD salvage cycle to produce nicotinic acid via the conversion of nicotinamide by the enzyme nicotinamidase.
The N-methyl-?1-pyrrollidium cation used in the synthesis of nicotine is an intermediate in the synthesis of tropane-derived alkaloids. Biosynthesis begins with decarboxylation of ornithine by ornithine decarboxylase (ODC) to produce putrescine. Putrescine is then converted into N-methyl putrescine via methylation by SAM catalyzed by putrescine N-methyltransferase (PMT). N-methylputrescine then undergoes deamination into 4-methylaminobutanal by the N-methylputrescine oxidase (MPO) enzyme, 4-methylaminobutanal then spontaneously cyclize into N-methyl-?1-pyrrollidium cation.
The final step in the synthesis of nicotine is the coupling between N-methyl-?1-pyrrollidium cation and nicotinic acid. Although studies conclude some form of coupling between the two component structures, the definite process and mechanism remains undetermined. The current agreed theory involves the conversion of nicotinic acid into 2,5-dihydropyridine through 3,6-dihydronicotinic acid. The 2,5-dihydropyridine intermediate would then react with N-methyl-?1-pyrrollidium cation to form enantiomerically pure (–)-nicotine.
Pharmacology
Pharmacokinetics
As nicotine enters the body, it is distributed quickly through the bloodstream and crosses the blood–brain barrier reaching the brain within 10–20 seconds after inhalation.The elimination half-life of nicotine in the body is around two hours.
The amount of nicotine absorbed by the body from smoking depends on many factors, including the types of tobacco, whether the smoke is inhaled, and whether a filter is used. For chewing tobacco, dipping tobacco, snus and snuff, which are held in the mouth between the lip and gum, or taken in the nose, the amount released into the body tends to be much greater than smoked tobacco. Nicotine is metabolized in the liver by cytochrome P450 enzymes (mostly CYP2A6, and also by CYP2B6). A major metabolite is cotinine.
Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.Under some conditions, other substances may be formed such as myosmine.
Glucuronidation and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine in vivo.
Detection of use
Medical detection
Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a medicolegal death investigation. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids.Nicotine use is not regulated in competitive sports programs, yet the drug has been shown to have a significant beneficial effect on athletic endurance in subjects who have not used nicotine before.
Pharmacodynamics
Nicotine acts on the nicotinic acetylcholine receptors, specifically the ganglion type nicotinic receptor and one CNS nicotinic receptor. The former is present in the adrenal medulla and elsewhere, while the latter is present in the central nervous system (CNS). In small concentrations, nicotine increases the activity of these receptors. Nicotine also has effects on a variety of other neurotransmitters through less direct mechanisms.
In the central nervous system
By binding to nicotinic acetylcholine receptors, nicotine increases the levels of several neurotransmitters – acting as a sort of "volume control". It is thought that increased levels of dopamine in the reward circuits of the brain are responsible for the apparent euphoria and relaxation, and addiction caused by nicotine consumption. Nicotine has a higher affinity for acetylcholine receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis.Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.
Other primary metabolites include nicotine N'-oxide, nornicotine, nicotine isomethonium ion, 2-hydroxynicotine and nicotine glucuronide.Under some conditions, other substances may be formed such as myosmine.
Glucuronidation and oxidative metabolism of nicotine to cotinine are both inhibited by menthol, an additive to mentholated cigarettes, thus increasing the half-life of nicotine in vivo.
Detection of use
Medical detection
Nicotine can be quantified in blood, plasma, or urine to confirm a diagnosis of poisoning or to facilitate a medicolegal death investigation. Urinary or salivary cotinine concentrations are frequently measured for the purposes of pre-employment and health insurance medical screening programs. Careful interpretation of results is important, since passive exposure to cigarette smoke can result in significant accumulation of nicotine, followed by the appearance of its metabolites in various body fluids.Nicotine use is not regulated in competitive sports programs, yet the drug has been shown to have a significant beneficial effect on athletic endurance in subjects who have not used nicotine before.
Pharmacodynamics
Nicotine acts on the nicotinic acetylcholine receptors, specifically the ganglion type nicotinic receptor and one CNS nicotinic receptor. The former is present in the adrenal medulla and elsewhere, while the latter is present in the central nervous system (CNS). In small concentrations, nicotine increases the activity of these receptors. Nicotine also has effects on a variety of other neurotransmitters through less direct mechanisms.
In the central nervous system
By binding to nicotinic acetylcholine receptors, nicotine increases the levels of several neurotransmitters – acting as a sort of "volume control". It is thought that increased levels of dopamine in the reward circuits of the brain are responsible for the apparent euphoria and relaxation, and addiction caused by nicotine consumption. Nicotine has a higher affinity for acetylcholine receptors in the brain than those in skeletal muscle, though at toxic doses it can induce contractions and respiratory paralysis.Nicotine's selectivity is thought to be due to a particular amino acid difference on these receptor subtypes.
Tobacco smoke contains anabasine, anatabine, and nornicotine. It also contains the monoamine oxidase inhibitors harman and norharman.These beta-carboline compounds significantly decrease MAO activity in smokers.MAO enzymes break down monoaminergic neurotransmitters such as dopamine, norepinephrine, and serotonin. It is thought that the powerful interaction between the MAOIs and the nicotine is responsible for most of the addictive properties of tobacco smoking.The addition of five minor tobacco alkaloids increases nicotine-induced hyperactivity, sensitization and intravenous self-administration in rats.
Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions but not habenulopeduncular structures.Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.
Chronic nicotine exposure via tobacco smoking up-regulates alpha4beta2* nAChR in cerebellum and brainstem regions but not habenulopeduncular structures.Alpha4beta2 and alpha6beta2 receptors, present in the ventral tegmental area, play a crucial role in mediating the reinforcement effects of nicotine.
In the sympathetic nervous system
Nicotine also activates the sympathetic nervous system,acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream. Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or due to the irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals. However, further research is warranted before a definite conclusive link can be inferred.
Nicotine also activates the sympathetic nervous system,acting via splanchnic nerves to the adrenal medulla, stimulates the release of epinephrine. Acetylcholine released by preganglionic sympathetic fibers of these nerves acts on nicotinic acetylcholine receptors, causing the release of epinephrine (and norepinephrine) into the bloodstream. Nicotine also has an affinity for melanin-containing tissues due to its precursor function in melanin synthesis or due to the irreversible binding of melanin and nicotine. This has been suggested to underlie the increased nicotine dependence and lower smoking cessation rates in darker pigmented individuals. However, further research is warranted before a definite conclusive link can be inferred.
In adrenal medulla
By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.
Nicotine is the natural product of tobacco, having a half-life of 1 to 2 hours. Cotinine is an active metabolite of nicotine that remains in the blood for 18 to 20 hours, making it easier to analyze due to its longer half-life.
Psychoactive effects
Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness. Like any stimulant, it may very rarely cause the often catastrophically uncomfortable neuropsychiatric effect of akathisia. By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.
When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates the release of many chemical messengers such as acetylcholine, norepinephrine, epinephrine, vasopressin, histamine, arginine, serotonin, dopamine, autocrine agents, and beta-endorphin.This release of neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance concentration and memory due to the increase of acetylcholine. It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine. Arousal is increased by the increase of norepinephrine. Pain is reduced by the increases of acetylcholine and beta-endorphin. Anxiety is reduced by the increase of beta-endorphin. Nicotine also extends the duration of positive effects of dopamine and increases sensitivity in brain reward systems.Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.
Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.This stimulates nerve transmission. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of nerve impulses, producing a mild sedative effect. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of psychostimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use.
Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties. However, after coadministration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential. This is similar in effect to amphetamine.
Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are available, as well as smokeless tobacco, nicotine lozenges and electronic cigarettes.
By binding to ganglion type nicotinic receptors in the adrenal medulla nicotine increases flow of adrenaline (epinephrine), a stimulating hormone and neurotransmitter. By binding to the receptors, it causes cell depolarization and an influx of calcium through voltage-gated calcium channels. Calcium triggers the exocytosis of chromaffin granules and thus the release of epinephrine (and norepinephrine) into the bloodstream. The release of epinephrine (adrenaline) causes an increase in heart rate, blood pressure and respiration, as well as higher blood glucose levels.
Nicotine is the natural product of tobacco, having a half-life of 1 to 2 hours. Cotinine is an active metabolite of nicotine that remains in the blood for 18 to 20 hours, making it easier to analyze due to its longer half-life.
Psychoactive effects
Nicotine's mood-altering effects are different by report: in particular it is both a stimulant and a relaxant.First causing a release of glucose from the liver and epinephrine (adrenaline) from the adrenal medulla, it causes stimulation. Users report feelings of relaxation, sharpness, calmness, and alertness. Like any stimulant, it may very rarely cause the often catastrophically uncomfortable neuropsychiatric effect of akathisia. By reducing the appetite and raising the metabolism, some smokers may lose weight as a consequence.
When a cigarette is smoked, nicotine-rich blood passes from the lungs to the brain within seven seconds and immediately stimulates the release of many chemical messengers such as acetylcholine, norepinephrine, epinephrine, vasopressin, histamine, arginine, serotonin, dopamine, autocrine agents, and beta-endorphin.This release of neurotransmitters and hormones is responsible for most of nicotine's effects. Nicotine appears to enhance concentration and memory due to the increase of acetylcholine. It also appears to enhance alertness due to the increases of acetylcholine and norepinephrine. Arousal is increased by the increase of norepinephrine. Pain is reduced by the increases of acetylcholine and beta-endorphin. Anxiety is reduced by the increase of beta-endorphin. Nicotine also extends the duration of positive effects of dopamine and increases sensitivity in brain reward systems.Most cigarettes (in the smoke inhaled) contain 1 to 3 milligrams of nicotine.
Research suggests that, when smokers wish to achieve a stimulating effect, they take short quick puffs, which produce a low level of blood nicotine.This stimulates nerve transmission. When they wish to relax, they take deep puffs, which produce a high level of blood nicotine, which depresses the passage of nerve impulses, producing a mild sedative effect. At low doses, nicotine potently enhances the actions of norepinephrine and dopamine in the brain, causing a drug effect typical of those of psychostimulants. At higher doses, nicotine enhances the effect of serotonin and opiate activity, producing a calming, pain-killing effect. Nicotine is unique in comparison to most drugs, as its profile changes from stimulant to sedative/pain killer in increasing dosages and use.
Technically, nicotine is not significantly addictive, as nicotine administered alone does not produce significant reinforcing properties. However, after coadministration with an MAOI, such as those found in tobacco, nicotine produces significant behavioral sensitization, a measure of addiction potential. This is similar in effect to amphetamine.
Nicotine gum, usually in 2-mg or 4-mg doses, and nicotine patches are available, as well as smokeless tobacco, nicotine lozenges and electronic cigarettes.
Side Effects
Nicotine increases blood pressure and heart rate in humans.Nicotine can stimulate abnormal proliferation of vascular endothelial cells, similar to that seen in atherosclerosis. Nicotine induces potentially atherogenic genes in human coronary artery endothelial cells.Nicotine could cause microvascular injury through its action on nicotinic acetylcholine receptors (nAChRs), however other mechanisms are also likely at play.
A study on rats showed that nicotine exposure abolishes the beneficial and protective effects of estrogen on the hippocampus,an estrogen-sensitive region of the brain involved in memory formation and retention.
Dependence and withdrawal
Modern research shows that nicotine acts on the brain to produce a number of effects. Specifically, research examining its addictive nature has been found to show that nicotine activates the mesolimbic pathway ("reward system") – the circuitry within the brain that regulates feelings of pleasure and euphoria.
Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin. Like other physically addictive drugs, nicotine withdrawal causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine regulates the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in norepinephrine, one of the successors to dopamine, which inhibit reuptake of the glutamate receptors,in charge of memory and cognition. The net effect is an increase in reward pathway sensitivity, the opposite of other addictive drugs such as cocaine and heroin, which reduce reward pathway sensitivity. This neuronal brain alteration can persist for months after administration ceases.
A study found that nicotine exposure in adolescent mice retards the growth of the dopamine system, thus increasing the risk of substance abuse during adolescence.
Nicotine increases blood pressure and heart rate in humans.Nicotine can stimulate abnormal proliferation of vascular endothelial cells, similar to that seen in atherosclerosis. Nicotine induces potentially atherogenic genes in human coronary artery endothelial cells.Nicotine could cause microvascular injury through its action on nicotinic acetylcholine receptors (nAChRs), however other mechanisms are also likely at play.
A study on rats showed that nicotine exposure abolishes the beneficial and protective effects of estrogen on the hippocampus,an estrogen-sensitive region of the brain involved in memory formation and retention.
Dependence and withdrawal
Modern research shows that nicotine acts on the brain to produce a number of effects. Specifically, research examining its addictive nature has been found to show that nicotine activates the mesolimbic pathway ("reward system") – the circuitry within the brain that regulates feelings of pleasure and euphoria.
Dopamine is one of the key neurotransmitters actively involved in the brain. Research shows that by increasing the levels of dopamine within the reward circuits in the brain, nicotine acts as a chemical with intense addictive qualities. In many studies it has been shown to be more addictive than cocaine and heroin. Like other physically addictive drugs, nicotine withdrawal causes down-regulation of the production of dopamine and other stimulatory neurotransmitters as the brain attempts to compensate for artificial stimulation. As dopamine regulates the sensitivity of nicotinic acetylcholine receptors decreases. To compensate for this compensatory mechanism, the brain in turn upregulates the number of receptors, convoluting its regulatory effects with compensatory mechanisms meant to counteract other compensatory mechanisms. An example is the increase in norepinephrine, one of the successors to dopamine, which inhibit reuptake of the glutamate receptors,in charge of memory and cognition. The net effect is an increase in reward pathway sensitivity, the opposite of other addictive drugs such as cocaine and heroin, which reduce reward pathway sensitivity. This neuronal brain alteration can persist for months after administration ceases.
A study found that nicotine exposure in adolescent mice retards the growth of the dopamine system, thus increasing the risk of substance abuse during adolescence.
Some have been able to re-start their natural dopamine production and bypass months or years of depression caused by nicotine withdrawal by using a combination of 2 over-the-counter supplements: 5-HTP (5-Hydroxytryptophan also known as oxitriptan) and L-Tyrosine (para-hydroxyphenylalanine). Studies of the combination have been conducted only on general depression[68] and no one has yet measured the effects specifically on nicotine withdrawal-related depression. However, anecdotal evidence suggests that the combination can be effective. In addition to being a natural and low-cost alternative to prescription anti-depressants, this protocol also has the benefit of being short-term in that the treatment is only necessary for a few months after nicotine abatement. Certain side effects, especially negative drug interactions, have been found with 5-HTP, so this treatment should not be undertaken in combination with any prescription medication or without specific approval from a doctor.
Immunology prevention
Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed. The principle is under the premise that if an antibody is attached to a nicotine molecule, it will be prevented from diffusing through the capillaries, thus making it less likely that it ever affects the brain by binding to nicotinic acetylcholine receptors.
These include attaching the nicotine molecule as a hapten to a protein carrier such as Keyhole limpet hemocyanin or a safe modified bacterial toxin to elicit an active immune response. Often it is added with bovine serum albumin.
Additionally, because of concerns with the unique immune systems of individuals being liable to produce antibodies against endogenous hormones and over the counter drugs, monoclonal antibodies have been developed for short term passive immune protection. They have half-lives varying from hours to weeks. Their half-lives depend on their ability to resist degradation from pinocytosis by epithelial cells.
Toxicology
The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans.Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine, which has an LD50 of 95.1 mg/kg when administered to mice. It is unlikely that a person would overdose on nicotine through smoking alone, although overdose can occur through combined use of nicotine patches or nicotine gum and cigarettes at the same time.Spilling a high concentration of nicotine onto the skin can cause intoxication or even death, since nicotine readily passes into the bloodstream following dermal contact.
Historically, nicotine has not been regarded as a carcinogen and the IARC has not evaluated nicotine in its standalone form and assigned it to an official carcinogen group. While no epidemiological evidence supports that nicotine alone acts as a carcinogen in the formation of human cancer, research over the last decade has identified nicotine's carcinogenic potential in animal models and cell culture.Nicotine has been noted to directly cause cancer through a number of different mechanisms such as the activation of MAP Kinases. Indirectly, nicotine increases cholinergic signalling (and adrenergic signalling in the case of colon cancer), thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-LOX, and EGF. Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), metastasis (nine-fold increase), and tumor recurrence (threefold increase).
Though the teratogenic properties of nicotine may or may not yet have been adequately researched, women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects, according to a study of around 77,000 pregnant women in Denmark. The study found that women who use nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60% greater risk of having babies with birth defects, compared to women who are non-smokers.[citation needed]
Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to the state to cause developmental toxicity, for the purposes of Proposition 65.
Immunology prevention
Because of the severe addictions and the harmful effects of smoking, vaccination protocols have been developed. The principle is under the premise that if an antibody is attached to a nicotine molecule, it will be prevented from diffusing through the capillaries, thus making it less likely that it ever affects the brain by binding to nicotinic acetylcholine receptors.
These include attaching the nicotine molecule as a hapten to a protein carrier such as Keyhole limpet hemocyanin or a safe modified bacterial toxin to elicit an active immune response. Often it is added with bovine serum albumin.
Additionally, because of concerns with the unique immune systems of individuals being liable to produce antibodies against endogenous hormones and over the counter drugs, monoclonal antibodies have been developed for short term passive immune protection. They have half-lives varying from hours to weeks. Their half-lives depend on their ability to resist degradation from pinocytosis by epithelial cells.
Toxicology
The LD50 of nicotine is 50 mg/kg for rats and 3 mg/kg for mice. 30–60 mg (0.5–1.0 mg/kg) can be a lethal dosage for adult humans.Nicotine therefore has a high toxicity in comparison to many other alkaloids such as cocaine, which has an LD50 of 95.1 mg/kg when administered to mice. It is unlikely that a person would overdose on nicotine through smoking alone, although overdose can occur through combined use of nicotine patches or nicotine gum and cigarettes at the same time.Spilling a high concentration of nicotine onto the skin can cause intoxication or even death, since nicotine readily passes into the bloodstream following dermal contact.
Historically, nicotine has not been regarded as a carcinogen and the IARC has not evaluated nicotine in its standalone form and assigned it to an official carcinogen group. While no epidemiological evidence supports that nicotine alone acts as a carcinogen in the formation of human cancer, research over the last decade has identified nicotine's carcinogenic potential in animal models and cell culture.Nicotine has been noted to directly cause cancer through a number of different mechanisms such as the activation of MAP Kinases. Indirectly, nicotine increases cholinergic signalling (and adrenergic signalling in the case of colon cancer), thereby impeding apoptosis (programmed cell death), promoting tumor growth, and activating growth factors and cellular mitogenic factors such as 5-LOX, and EGF. Nicotine also promotes cancer growth by stimulating angiogenesis and neovascularization. In one study, nicotine administered to mice with tumors caused increases in tumor size (twofold increase), metastasis (nine-fold increase), and tumor recurrence (threefold increase).
Though the teratogenic properties of nicotine may or may not yet have been adequately researched, women who use nicotine gum and patches during the early stages of pregnancy face an increased risk of having babies with birth defects, according to a study of around 77,000 pregnant women in Denmark. The study found that women who use nicotine-replacement therapy in the first 12 weeks of pregnancy have a 60% greater risk of having babies with birth defects, compared to women who are non-smokers.[citation needed]
Effective April 1, 1990, the Office of Environmental Health Hazard Assessment (OEHHA) of the California Environmental Protection Agency added nicotine to the list of chemicals known to the state to cause developmental toxicity, for the purposes of Proposition 65.
Therapeutic uses
The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.
However, in a few situations, smoking has been observed to apparently be of therapeutic value. These are often referred to as "Smoker’s Paradoxes". Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to tar and other ingredients found in tobacco.
For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention (PCI). Risk of ulcerative colitis has been frequently shown to be reduced by smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking. Smoking also appears to interfere with development of Kaposi's sarcoma in patients with HIV.
Nicotine has a mild laxative effect and can reduce symptoms of ulcerative colitis.
Nicotine reduces the chance of breast cancer among women carrying the very high risk BRCA gene, preeclampsia, and atopic disorders such as allergic asthma. A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.
Tobacco smoke has been shown to contain compounds capable of inhibiting monoamine oxidase, which is responsible for the degradation of dopamine in the human brain. When dopamine is broken down by MAO-B, neurotoxic by-products are formed, possibly contributing to Parkinson's and Alzheimers disease.
The primary therapeutic use of nicotine is in treating nicotine dependence in order to eliminate smoking with the damage it does to health. Controlled levels of nicotine are given to patients through gums, dermal patches, lozenges, electronic/substitute cigarettes or nasal sprays in an effort to wean them off their dependence.
However, in a few situations, smoking has been observed to apparently be of therapeutic value. These are often referred to as "Smoker’s Paradoxes". Although in most cases the actual mechanism is understood only poorly or not at all, it is generally believed that the principal beneficial action is due to the nicotine administered, and that administration of nicotine without smoking may be as beneficial as smoking, without the higher risk to health due to tar and other ingredients found in tobacco.
For instance, recent studies suggest that smokers require less frequent repeated revascularization after percutaneous coronary intervention (PCI). Risk of ulcerative colitis has been frequently shown to be reduced by smokers on a dose-dependent basis; the effect is eliminated if the individual stops smoking. Smoking also appears to interfere with development of Kaposi's sarcoma in patients with HIV.
Nicotine has a mild laxative effect and can reduce symptoms of ulcerative colitis.
Nicotine reduces the chance of breast cancer among women carrying the very high risk BRCA gene, preeclampsia, and atopic disorders such as allergic asthma. A plausible mechanism of action in these cases may be nicotine acting as an anti-inflammatory agent, and interfering with the inflammation-related disease process, as nicotine has vasoconstrictive effects.
Tobacco smoke has been shown to contain compounds capable of inhibiting monoamine oxidase, which is responsible for the degradation of dopamine in the human brain. When dopamine is broken down by MAO-B, neurotoxic by-products are formed, possibly contributing to Parkinson's and Alzheimers disease.
Many such papers regarding Alzheimer's disease and Parkinson's Disease have been published. While tobacco smoking is associated with an increased risk of Alzheimer's disease, there is evidence that nicotine itself has the potential to prevent and treat Alzheimer's disease.Nicotine has been shown to delay the onset of Parkinson's disease in studies involving monkeys and humans. A study has shown a protective effect of nicotine itself on neurons due to nicotine activation of a7-nAChR and the PI3K/Akt pathway which inhibits apoptosis-inducing factor release and mitochondrial translocation, cytochrome c release and caspase 3 activation.
Recent studies have indicated that nicotine can be used to help adults suffering from autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are responsible for processing nicotine in the brain.
Studies suggest a correlation between smoking and schizophrenia, with estimates near 75% for the proportion of schizophrenic patients who smoke. Although the nature of this association remains unclear, it was recently argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. More recent research has found that mildly dependent users got some benefit from nicotine, but not those who were highly dependent. There is very little research done on this subject, including the research by Duke University Medical Centre which found that nicotine may improve the symptoms of depression in people. Nicotine appears to improve ADHD symptoms. Some studies are focusing on benefits of nicotine therapy in adults with ADHD.
While acute/initial nicotine intake causes activation of nicotine receptors, chronic low doses of nicotine use leads to desensitisation of nicotine receptors (due to the development of tolerance) and results in an antidepressant effect, with research showing low dose nicotine patches being an effective treatment of major depressive disorder in non-smokers.
Nicotine (in the form of chewing gum or a transdermal patch) is being explored as an experimental treatment for OCD. Small studies show some success, even in otherwise treatment-refractory cases.
The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease.
Recent studies have indicated that nicotine can be used to help adults suffering from autosomal dominant nocturnal frontal lobe epilepsy. The same areas that cause seizures in that form of epilepsy are responsible for processing nicotine in the brain.
Studies suggest a correlation between smoking and schizophrenia, with estimates near 75% for the proportion of schizophrenic patients who smoke. Although the nature of this association remains unclear, it was recently argued that the increased level of smoking in schizophrenia may be due to a desire to self-medicate with nicotine. More recent research has found that mildly dependent users got some benefit from nicotine, but not those who were highly dependent. There is very little research done on this subject, including the research by Duke University Medical Centre which found that nicotine may improve the symptoms of depression in people. Nicotine appears to improve ADHD symptoms. Some studies are focusing on benefits of nicotine therapy in adults with ADHD.
While acute/initial nicotine intake causes activation of nicotine receptors, chronic low doses of nicotine use leads to desensitisation of nicotine receptors (due to the development of tolerance) and results in an antidepressant effect, with research showing low dose nicotine patches being an effective treatment of major depressive disorder in non-smokers.
Nicotine (in the form of chewing gum or a transdermal patch) is being explored as an experimental treatment for OCD. Small studies show some success, even in otherwise treatment-refractory cases.
The relationship between smoking and inflammatory bowel disease is now firmly established but remains a source of confusion among both patients and doctors. It is negatively associated with ulcerative colitis but positively associated with Crohn's disease. In addition, it has opposite influences on the clinical course of the two conditions with benefit in ulcerative colitis but a detrimental effect in Crohn's disease.
credit to wikipedia.org
Tuesday 16 October 2012
Lose Weight With Green Coffee Bean - Helpful Product Information
Product Features
-800mg of Green Coffee Bean Extract.
-Raspberry Ketones ~ includes 100mg recommended by Doctors
-Un-roasted top quality green coffee beans ensuring the highest form of Chlorogenic Acid!
-Raspberry Ketones & Coffee Extract ~ 2 diet products in 1 bottle!
-Lose Weight Without Diet Or Exercise! Virtually No Side Effects!
IMPORTANT INFORMATION
Safety Information
These statements have not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease. As always, we encourage you to speak to your physician prior to beginning any new supplements.
Indications
Intended for weight loss
Ingredients
Each bottle contains 60 910mg capsules. Each capsule contains 800mg Pure Green Coffee Bean Extract ~ 100mg Pure Raspberry Ketone ~ 10mg proprietary formula consisting of African Mango Extract, Acai Fruit, Resveratrol, Apple Cider Vinegar (powder), Kelp, Grapefruit (powder). Other Ingredients: Gelatin, Calcium Carbonate, Magnesium Stearate
Directions
Take one capsule (910 Mg) twice daily 30 minutes before a meal with 8 ounce of water.
PRODUCT INFORMATION
Pure Green Coffee Bean Extract Max has 800mg of PURE GREEN COFFEE BEAN EXTRACT with zero additives. It also contains 100mg of PURE RASPBERRY KETONES plus 10mg of various additives (see ingredients) which have been proven effective within the scientific community. All ingredients are all natural with virtually no side effects!"
The key ingredient in the green coffee bean is a very important natural active compound called chlorogenic acid. Chlorogenic acid works by inhibiting the release of glucose in the body, while at the same time boosting the metabolism or the "burning" of fat in the liver. These two mechanisms work together to inhibit the absorption of fat and eliminate weight gain.
910 Mg! Includes 800 Mg of Pure Green Coffee Bean Extract plus 100 Mg of Raspberry Ketones! With the combination of both you are sure to lose weight, Feel Great, and boost metabolism! Plus a 10mg proprietary formula of African Mango Extract (Irvingia Gabonensis),Acai Fruit, Resveratrol, Apple Cider Vinegar (powder), Kelp, Grapefruit (powder), Kelp, and Grapefruit (powder)!
Upon purchase of this product you will receive an email with a downloadable Food Journal to print for your own records.
MOST HELPFUL CUSTOMER REVIEWS
Good product, contains more than just green coffee bean extract July 23, 2012
By Joann Stout
I liked these capsules a lot. I tried another brand of pills in the past and literally nothing happened, no weight loss, no appetite suppression, nothing. This bottle lasted me 30 days exactly, and although didn't reach my weight loss goal I did lose some weight (about a pound a week) and did feel my appetite lower while taking these.
One thing to be aware of is these pills do contain other ingredients besides green coffee bean extract. If you are looking for only green coffee bean extract I suggest taking the powder, FREE Retinol Cream (Vitamin A 100,000 Iu Per Ounce) - 2 Oz With Pure Green Coffee Bean Extract Powder 50 Grams. I've been mixing them in my water bottle, which I'm currently doing, and in the couple weeks that I've been taking them i would have to say the appetite suppressant effects are about the same as the pills but the energy I feel from the powder is more noticeable. The other good thing is that I have lost four more pounds already so I think I finally have my metabolism speeding up because its only been two weeks since I started this new routine.
Tried 'em all June 21, 2012
By Ghandia
Gave this a 3 star because the price went up on this item to 24.99. Used one bottle already which was a 30 day supply. Tried different extracts since I heard about this a couple months ago. This is the only one that didn't upset my sensitive stomach and I couldn't be happier with the results. Just make sure you take it twice a day and on an empty stomach for maximum effectiveness.
Would have given it a 5 star because of its effectiveness, but didn't like that the price for a single bottle went up to 24.99. Hope you have the same success as us!!
So far this works great for me! July 11, 2012
By mary
Amazon Verified Purchase
Like many others I learned about green coffee extract on Dr. Oz with dietitian Lindsay Duncan. Decided to try it when I read that although only one small study study was completed, it was with humans. When I saw this blend with raspberry ketones (studies with animals only) I thought I would try it. I have been dieting for 6-8 weeks (WW) and have had anemic results of half pound to one pound a week while working out like a fiend 3-5 times week. I have not been taking this supplement for a full week yet and have lost 3 pounds! I WILL be ordering this again!!! I know that not everyone will get results (I've tried other supplements) but I am getting results. BTW...it hasn't done anything for cravings, portion control etc...just some good fat burning. The original study was for 12 weeks. I am not sure if that means one should only use it for 12 weeks but will most likely be taking a break after 12 weeks. If anyone sees results from additional studies I would appreciate a heads up.
credit : amazon.com
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