The putative ability of fish oils to affect cardiovascular health has focused considerable attention on lipid nutriture. Investigations of societies consuming high levels of omega-3 and -9 oils as well as both prospective and retrospective scientific studies have demonstrated the increasing importance of dietary fats.1-6 Complex mechanisms have been theorized but ultimately hinge on eicosanoid synthesis pathways. Fatty acids and other lipid substances such as cholesterol found within the circulation and as a part of the endothelial lining of blood vessels and their smooth muscle coat, and within platelets, provide an important substrate for vascular health or disease.
PLATELETS Platelets play a pivotal role in the relationship between lipids and atherogenesis. Blood platelets are powerful biochemical packages wrapped in a phospholipid membrane. When platelets in the circulation are exposed to broken endothelial tissue lining blood vessels and underlying collagen. they become activated to stimulate the healing of the injury.
The arachidonic acid within the platelet forms two different eicosanoids, which serve two opposing functions. If the platelet is next to another platelet, thromboxane (TXA2) is formed (500 million platelets can form as much as 2 mg of thromboxane) which stimulates the aggregation and clotting of platelets and other blood components.7 For those platelets near the endothelium, prostaglandin E2 (PGE2) is formed which stimulates hyperplasia in the exposed blood vessel tissue and inhibits further clotting adjacent to the injury. Prostaglandins also stimulate bone resorption bringing calcium to the site of the injury to decrease tissue pH and further stimulate hyperplasia.
These are normal mechanisms occurring continually and are essential to life. If they did not occur, minor vascular lesions could lead to runaway hemorrhage, and healing and repair would not happen. However, when there is an excess of omega-6 fatty acids in platelets which can generate excess amounts of arachidonic acid at blood vessel injury sites, the blood clotting, vessel constricting, bone resorbing, and hyperplastic effects can exceed the countering moderating effects of prostaglandins from fatty acids such as the omega-3's.
PATHOGENESIS High levels of dietary fat can result in high levels of low density lipoprotein (LDL). These protein-lipid complexes can contain large amounts of cholesterol, much of which can be oxidized as a result of the way modern foods are processed.8 LDL can migrate to areas of injury, be engulfed by monocytes and macrophages, and accumulate at the site of these injuries to provide more arachidonic acid and free radical generating oxidized cholesterol fuel for further endothelium damage.
This ongoing cycle, beginning with perhaps a small lesion which occurs as a matter of course in the endothelium, or induced injury as a result of high blood levels of oxidized fats, may turn out to be a self-perpetuating, out-of-control, cancerlike growth accumulating in vessels resulting in atheromas and eventual closure of coronary vessels leading to heart attacks. Additionally, hardening (sclerosis) of the arteries can result in hypertension and loss of vascular resiliency, potentially causing stroke, aneurysms, general loss of health and vigor, and predisposition to a range of other diseases.
In other words, if there is vascular injury, the normal clotting, vessel constricting, tissue regenerating mechanisms can run out of control as a result of an imbalance of moderating e1cosanoids which are ultimately derived from dietary lipids. In tissue with excess arachidonic cascade potential, vessel injury recruits excess platelets, which stimulate excess clotting, vessel constriction and vessel wall inflammation,
which in turn releases more arachidonic cascade eicosanoids, which stimulate further platelet aggregation, clotting and so on, leading to atheroma and vessel closure.
If there is no initial endothelial injury but it is being induced from high oxidized lipid blood levels, a similar cycle occurs. Oxidized LDL's are scavenged by monocytes which become macrophages, which accumulate within the vessel wall causing free radical damage, foam cell formation, calcium deposition and inflammation. This produces arachidonic cascade metabolites, which further induce inflammation leading to progressive atheroma and vessel closure. (Fig. 26, 27)
PREVENTION RATIONALE An alteration of the diet such that oxidized fats are decreased, saturated fats are decreased, omega-6 fats are decreased (in Western societies), and omega-3 and omega-9 rich foods are increased may potentially result in a restoration of health to the vessel wall. Prostaglandins created by omega-3 and omega-9 oils create opposite effects to the vessel constricting, clot-forming effects of the omega-6 oils since they compete for the same enzyme system. (Refer to Fig. 18) Therefore, if omega-3 and -9 fatty acids are increased in the diet, they use up the enzyme systems normally used byarachidonic acid to form the atherogenic promoting eicosanoids. This is the present explanation for the epidemiological evidence showing that humans and animals consuming higher levels of the omega-3 and omega-9 classes of fatty acids develop far less of the common cardiovascular problems than exist in Western society.
There is some evidence that the incidence of cardiovascular disease is proportional to the ratios of fatty acid classes in platelets, which is in turn related to diet. Eskimos, for example, have a higher omega-3 to omega-6 ratio in their tissues reflecting their high fish diet, which is in turn related to their low risk of cardiovascular disease compared to Western nations. (Fig. 28)
[ The Formation Of Atheroma Image ] http://www.wysong.net/articles/lipid/figures/figure27.jpg
This is not to say omega-6 fatty acids such as linoleic are harmful per se. Balance is key. Indeed if sufficient linoleic is not present, atherosclerosis can result as evidenced in a variety of species.9,10
ASPIRIN By shifting the balance of these same eicosanoid enzyme systems, aspirin is also believed to exert its effect as an anticlotting agent in cardiovascular disease. Aspirin is a specific inhibitor (acetylator) of cyclooxygenase which normally is used to convert arachidonic acid into TXA2 and PGE2. Aspirin's inhibition of clot forming TXA2 is several days longer than its effect on anticoagulating and vasodilating PGE2. Thus the net effect is clot inhibition. (Refer to Fig. 19)
However, aspirin is a bandage. It does not address the root cause, which is dietary impropriety. It is also not without its dangers since it can precipitate allergic reactions such as asthma by shunting arachidonic acid into the lipoxygenase leukotriene path and may actually increase platelet clotting if given in conjunction with fish oils.11
Excess consumption of oxidized fats and fatty acids of the omega-6 family will fuel the atherosclerotic system. Excess raw materials can exceed the ability of moderators. If the root cause is dietary, the ultimate solution must therefore also be dietary, not pharmacologic. It is ironic that the 80 million aspirin tablets taken daily by Americans may in large part be necessary to cancel the effects of 15 million pounds of omega-6-predominant processed polyunsaturated oils.
NUTRIENTS Many nutrients found within foods have the ability to block or modulate prostaglandin synthesis. These include sulfur compounds found in garlic, onions and cruciferous vegetables, and various minerals, particularly the divalent cations zinc, copper, lithium, silver, selenium, and calcium.12 A variety of fresh whole foods, (raw if possible) grown on nutrient-rich soils (as opposed to modern agribusiness mined soils where only nitrogen, phosphorus and potassium -- NPK fertilizers -- are replaced) provides the body with raw materials which augment proper fatty acid nutrition and may lessen or obviate the need for potentially dangerous drugs.
Other nonpharmacologic factors which may help produce more "friendly" lipid profiles include decreased stress, increased exercise and the elimination of tobacco and perhaps caffeine.13 Highly refined carbohydrate and sugar diets increase cardiovascular disease risk perhaps through increased glycosylation reactions, increased lipoprotein (a) levels and decreasing HDL levels.14 Calcium at 800 mg per day can decrease cholestero1.15 Chromium deficiency can decrease glucose tolerance factor and thus affect sugar metabolism and adversely affect lipid proflies.16Legumes, soluble fiber, garlic and onions can decrease cholesterol levels.17 Vitamin C at 1000 mg per day and vitamin E at 200-400 I.U. per day are excellent antioxidants and can decrease glycosylation reactions, decrease cholesterol and increase HDL'S.18 Pantethine, a derivative of pantothenic acid at 300 mg. 3-4 times daily,19 and niacin from 1-4 grams daily can positively affect lipids. Niacin in fact is one of the few agents capable of lowering genetically controlled Lp(a) levels.20 L-carnitine, an amino acid, at 1000 mg per day can ameliorate hyperlipoproteinemia.21
These nutrients are supplied in a varied whole raw food diet. Some researchers argue, however, that therapeutic levels of some nutrients are not possible from simply consuming natural foods. An accumulated deficit from a lifetime of dietary indiscretion may indeed require a boost. Disease, an extraordinary event, may require extraordinary measures to effect a cure. But before consuming any isolated nutrient become well aware of its merits and demerits since some nutrients can present toxicities or imbalances at certain levels. Guidance by a well qualified nutritional health care professional would be advised for anyone with existing disease who desires to use isolated nutrients in therapy.
As mentioned in the previous chapter, the case for the link between diet and heart disease is not closed. Some argue that the diet-heart hypothesis began, remains, and grows because of the support of powerful institutions and personalities who subserve gigantic health-disease and food industries.22 Some have calculated that for persons aged 20-62 that a lifelong program of cholesterol reduction might increase life expectancy three days to thirty months.23 Even Sir William Osler, the most highly respected physician of his time, said in 1879 that arterial degeneration could occur even at a young age and was due to "the high pressure in which men live, and habit of working the machine to its maximum capacity," not to excesses in eating and drinking. 24
There is little doubt that singular focus on diet or exercise, for example, misses the mark. It ignores equally important factors such as self esteem, affectionate relationships and feeling in control of one's life.25 The controversy aside, living and eating in a more natural synergonic context can only help and is likely the greatest potential for life free from disease.
References available within book text, click the following link to view this article on wysong.net: http://www.wysong.net/articles/lipid/08_article_lipid_chapter_eight_atherogenesis.shtml
For further reading, or for more information about, Dr Wysong and the Wysong Corporation please visit www.wysong.net or write to wysong@wysong.net. For resources on healthier foods for people including snacks, and breakfast cereals please visit www.cerealwysong.com.
At its core, Email Marketing is a tool for customer relationship management (CRM). Its Purpose: To build virtual relationships with existing and potential customers. Its Benefit: Maximise the retention and value of these customers, which should ultimately lead to greater profitability. What is Email Marketing? Simply put, Email Marketing is a form of direct marketing which utilises electronic means to deliver commercial messages to an audience. It is one of the oldest and yet still one of the most powerful of all eMarketing tactics. The power comes from the fact that it is: •extremely cost effective and has a low cost per contact •highly targeted •customisable •completely measurable Email Marketing's main strength is that it takes advantage of a customer's most prolific touch point with the Internet… their inbox. Although spam mail has done a great deal to discredit the Email Marketing industry, the benefits are still apparent and substantiated by the fact that in February, 2006, a JupiterResearch report concluded that spending on Email Marketing will rise from $885 million in 2005 to $1.1 billion in 2010. Email Marketing - A Step By Step Guide A successful email campaign requires careful attention - from planning to execution and evaluation of the campaign. There are certain best practices and steps to follow which will ensure the success of an email campaign: Step 1 - Strategic Planning The first part of any email campaign should involve planning around the goals you will need to achieve. There are roughly 2 types of commercial emails you can send: •Promotional emails are more direct and are geared at enticing the user to take action through purchase or sign up •Retention based emails usually take the form of a newsletter and may include promotional messages but ultimately should contain information of value to create a long term relationship with the reader A successful email campaign is most likely to be the one geared at retaining and creating a long term relationship with the reader. Step 2 - List Building and Management Running a successful email campaign requires that your business has a genuine opt-in database. This means that you need to have the user's permission to communicate with them or you risk having your mail regarded as spam or unsolicited (bulk) email. Emails regarded as spam can have dire consequences for your organisation as not only will your reputation be in jeopardy, but legal action may be pursued in many parts of the world. An effective, best practice Email Marketing campaign requires an in-house list cultivated over time. This list should contain people who are prospects, customers or potential evangelists of your business, who have explicitly given their permission to hear from you. You can use the website, subscription campaigns as well as the newsletter itself (e.g. send to a friend function) to build lists. An equally important feature is the unsubscribe function. A reader needs to know how they can easily opt-out of your email communication should they need to. Step 3 - Creative Execution Email content that your readers will value is vital to ensuring the success of an Email Marketing campaign. Valuable content is informative and progressive and should address the problems and needs of readers. Its all about what they want to hear more than what you want to say to them. The reader determines what value your content provides, not the publisher. Step 4 - Design The design of a mailer is sometimes an area that has the least amount of thought put into it. This is usually due to the lack of understanding some designers have of usability. The common problems are the: •length of the email •disorganised structure of information •readability of text Interactive emails are best constructed with lightweight HTML capability allowing the email to open quickly in order to grab the user's attention before he/she moves on. The structure must allow people to scan and navigate the email without too much complication. The length of paragraphs, emphasis through bolding and colours as well as sectioning information with bullets and borders all contribute to a well structured email. Any good designer will test their email on a variety of current, most used email clients. (E.g. Outlook, Thunderbird, Lotus Notes, Eudora etc). This process is called platform testing and ensures that the email will display correctly in as many email clients as possible. Sometimes it is not possible to ensure exact consistency on every email client; however the variations can be minimised through following best international practice and staying abreast of new developments in email clients. Step 5 - Newsletter Components Within every newsletter, there are a number of components that will aid the reader to orientate and better accept and react to your newsletter over time. Consistency is key in some areas while others can be refreshed although remaining within the style and tone of the communication. The most prevalent components are as follows: •Subject Lines are essential! They aid the reader in identifying the newsletter and enticing them to open it. It is important to avoid promotional words like "free", "win" and "buy now" due to these being flagged as potential spam by email spam filters. Using the name and edition of the newsletter in the subject line aids in maintaining consistency and also helps readers filter them from their inbox. •"To"," from" and "reply" fields are also opportunities to build the relationship through creating a perception of familiarity. In other words, the reader needs to perceive that the newsletter is somewhat unique for them and sent personally by the publisher. Using a personalised company email address for the "reply" field creates familiarity and builds trust with the reader. The "from" address should also include the organisation's name. A meaningless "from" address which the reader cannot identify only serves to confuse the origin of the newsletter. •Personalisation should be standard practice with emails. However, some companies still start the newsletter with a greeting like "Dear Valued Guest". This can be acceptable as a default greeting; however, using their first name or surname can create a perception of a more personal email. This can be taken further if the customers give you a preference regarding the content they like the most. The text and images in the email can be tailored to match preferences and interests upon delivery. Step 6 - Deployment Any good email marketer should be able to ensure an excellent delivery rate. A challenge for email marketers today is getting past the various spam filters on the path to the readers inbox. It is worthwhile to check emails against various spam filters, like Spamassasin, to ensure your legitimate message is not mistakenly picked up by one of them. Delivering emails at correct and consistent times also contributes to the reader fostering a relationship with your organisation. A good offline example of this relationship is the daily newspaper delivery which arrives at your door at the same time every day, week or month. Step 7 - Tracking and Reporting It is crucial to determine the success of your email campaign on the short and long term basis. For this you will need an email tracking system which produces statistics in a user friendly manner. It is important that these statistics are used in a way which improves and refines the email campaign to boost your goals and return on investment (ROI). The following measurables contribute to your understanding of the performance of email campaigns: •Subscriber Growth vs. Decline - Tracking the growth or shrinkage of your database can help you analyse what is or what is not working in a newsletter. A significant or consistent loss in subscribers is a key indication that you are not meeting the needs of your subscribers. A high pass on rate indicates that your list values the content enough to constantly share with others. Splitting the list and testing 2 versions of the newsletter can help determine the cause of high unsubscribe rates. The size of the list however, is not as important as the quality thereof as a high percentage response from your existing newsletter recipients carries more impact than subscriber growth which may still yield low response rates. •Click Through Rates and Conversion - This measures the effectiveness of your email via the links placed therein. When a reader clicks through to a webpage, these can be easily measured as a percentage against number of delivered, opened or sent emails. By analysing these statistics, the email marketer will be able to tell which content or promotion was the most enticing for the reader. Measuring the click throughs and conversion rates will ensure that you are able to track differences and trends the same way over time in order to improve the newsletter content and its impact. •Feedback and Interaction Handling - The feedback from readers is probably the best way to gauge what impression your newsletter is making on them. If you are receiving regular positive feedback, chances are that many of your readers are impressed with the style and content of the newsletter. Evaluating what they are saying about you in other areas on the Internet will also help you get a better picture of the reputation of your brand online. •Split testing - This is one of the most important parts of an Email Marketing Campaign! Split testing across a host of factors like open rates across different subject lines, different days of the week and times of the day, different copy styles and email length, for example, will enable you to see what is working best for your campaign. In short there is no alternative to putting a lot of time and energy into testing and fine tuning your email marketing strategy - your open rates will improve and the results are well worth it! Well there you have it; we now know email marketing is controllable and measurable: making it one of the best means to ensure a return on your investment, by acquiring new customers and new sales.
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Dr. Randy Wysong has sinced written about articles on various topics from Health, Bankruptcy Chapter 11 and Bankruptcy Law. Dr. Wysong: A former veterinary clinician and surgeon, college instructor in human anatomy, physiology and the origin of life, inventor of numerous medical, surgical, nutritional, athletic and fitness products and devices, research director for the presen. Dr. Randy Wysong's top article generates over 22200 views. to your Favourites.
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