Departments of Otolaryngology, Radiation Oncology, and Immunology
Eye & Ear Institute
Pittsburgh, Pennsylvania
The method has been extensively employed to measure the calcification of stony corals (Jokiel & Coles erectile dysfunction blood pressure discount super p-force 160mg with mastercard, 1977; Jokiel et al erectile dysfunction pumps side effects discount 160 mg super p-force free shipping. However erectile dysfunction treatment buy cheap super p-force 160mg line, Davies (1989) compared the buoyant weight of two species of coral before and after stripping away the tissue and found that the soft tissue contributed 0 erectile dysfunction natural remedy cheap super p-force 160 mg otc. He recommended that a tissue weight correction be applied in order to obtain skeletal weights accurate to 1%. The method has generally been used to measure calcification over weekly intervals or longer, however, Davies (1989) used it to measure daily rates and even the difference between day and night rates. Caution should be exercised in applying the buoyant weighing method to the measurement of calcification in organisms other than corals where the contribution of soft tissue weight to the weight of the calcium carbonate parts may be substantial. Recent examples of studies employing the buoyant weighing method related to ocean acidification research include Marubini et al. The strengths of the buoyant weight method are that it is very simple, non-destructive, and easily applied to a large number of replicates. The major weakness of the method is that some of the increase in mass may not be due to building of new skeleton, i. This method is limited to the few species of coral that produce an annual high-density band that permits accurate dating of the skeleton (Figure 13. The distance between annual bands is a measure of the annual skeletal extension rate. Recent examples of studies employing the skeletal densitometry method related to ocean acidification research include Cooper et al. This method may also be useful for the study of calcification in molluscs that also produce skeletal density bands that may permit to estimate the age and the calcification rate of the shell. The strength of the skeletal density banding method is that it is the only method that can be applied to retrospective studies going back as much as 300 years. The main weakness of the method is that skeletal records are often very noisy requiring that the records from many organisms be averaged to obtain a significant result. Also, the method is limited to the few species that produce an annual skeletal density band and these species are not found in all environments. The strengths of the method are that it provides a direct measurement of calcification and it can easily handle a large number of replicates. These methods will be described below along with a mention of their strengths, weaknesses, precision and accuracy. Slack water, enclosure and mesocosm measurements Kinsey (1978b) described a method for measuring the calcification rate of a coral reef flat by observing the change in total alkalinity during a period of slack water at low tide. The only measurements that are needed are the total alkalinity and water depth at the beginning and end of the 1 to 3 h observation period. The method is only suitable for certain environments including tidal pools, crest pools, back reef environments, sand and reef flats, lagoonal environments and depressed centres of patch reefs ("micro-atolls"). It is also possible to use an enclosure to isolate the community to investigate (Kinsey, 1978b; Gattuso et al. Mesocosms provide a unique way to measure net calcification under controlled conditions (Figure 13. It is recommended to ensure that the system indeed is well mixed before using this approach. Most of what we know about seasonal changes in calcification at a particular site and the variability in calcification from reef to reef is based on the application of the slack-water method (Kinsey, 1978a,b). The ability to control the chemistry of the seawater within an enclosure placed over a portion of a natural community makes it the method of choice for studying the functional response of benthic community calcification to changes in carbonate chemistry (Yates & Halley, 2003, 2006; Figure 13. Where more control over environmental conditions is desired, a mesocosm with a well characterised community can be constructed. Fences or corrals can be used to achieve even finer scales studies of particular communities. The weakness of the slack-water method is that it is only possible to make measurements for a few hours out of the day, making daily rates difficult to obtain. Enclosures give freedom from the slack-water constraint, offer the possibility for manipulative experiments and can be placed over or around a specific community of interest. Mesocosms may offer a good compromise, permitting reproducibility as well as to derive accurate mass balances and control the physical and chemical conditions. The weakness of the mesocosm method is that the community under test is not completely natural but a subset of species that have been assembled to simulate the natural environment. Flow respirometry method the flow respirometry or upstream-downstream method described by Odum (1956) has been widely used to measure the primary production in rivers and streams. It has been adapted for the measurement of primary production and calcification of coral reefs (Marsh & Smith, 1978; Barnes, 1983; Griffith et al. Basically, the method involves the measurement of the chemical constituent of interest (O2, dissolved inorganic carbon or total alkalinity) immediately before a parcel of water begins its transit across a particular community and immediately downstream of the community. If the change in that chemical constituent of the water is divided by the water transit time, then the net rate at which the community alters that chemical constituent is determined. The method is limited to environments that experience unidirectional flow of water. It has been most widely applied to reef flats that experience unidirectional flow during periods of incoming and outgoing tide or as the result of set up caused by waves breaking out at the reef crest. It is also possible to find fringing coral reefs that experience seasonal unidirectional flow due to the existence of trade winds. If the sampling transect has biological zones which are broad and perpendicular to the direction of water flow (a reasonable assumption for many reef systems), then lateral mixing of water as it crosses the reef will not introduce a significant error into the estimate of the change in concentration along the transect. If observations are made at a fixed position over time the method is referred to as Eulerian. If observations are made with respect to the flowing parcel of water as it moves through the system of interest, the method is referred to as Lagrangian. This instrument was designed by the Australian Institute of Marine Science (photo credit: J. In addition, it is necessary to know the mean water depth along the transect and the current speed at the time of the observations. The Eulerian approach could be automated by the use of two autonomous water samplers and a current meter if one could be reasonably sure that flow would remain unidirectional for a period of time or if only water samples collected during periods of unidirectional flow were subsequently analysed based on analysis of the current direction data. The Lagrangian method has been automated by placing a pH and oxygen sensor on a drifting instrument package (Barnes et al. Of course the package still needs to be deployed at the start point of the transect over and over in order to develop the temporal data needed to estimate the daily rate. The strength of the method is that it measures community calcification under completely natural conditions. The weakness of the method is that it is limited to systems that experience unidirectional flow, does not account for lateral mixing (if biological zones are fairly broad then the lateral mixing term is probably small) and it is very laborious to obtain a daily rate. Alkalinity anomaly-water residence time method the alkalinity anomaly-water residence time method is suitable for lagoons, bays and banks where the residence time of the water is measured in days rather than hours. However, when the water residence time is measured in days to weeks they can become significant. However, groundwater is only likely to be important if the reef in question is associated with a landmass which has a large freshwater lens. From this, the spatially and temporally integrated calcification rate of the community can be computed as: # h G = "0. The water residence time, is defined as the time span over which a particular parcel of water remains in the system of interest. In the case where the flow of water is unidirectional, is the volume of water (m3) divided by the volume transport (m3 s-1) of that water across an imaginary vertical plane drawn through the system of interest. In practice, both the volume of water and the volume transport are expressed per unit width of reef perpendicular to the flow. In cases where the flow is more complex, other strategies need to be employed to obtain the residence time. Smith & Pesret (1974) and Smith & Jokiel (1978) used budgets of salt- and freshwater flux to estimate using the following equation (see also Gordon et al. The q term can be neglected if there is no river flow into the system or if groundwater flow is assumed to be negligible.
At higher dye concentrations impotence quotes the sun also rises buy 160mg super p-force visa, this two-wavelength approach reduces the concentration dependency of the measurements impotence natural treatment clary sage cheap 160 mg super p-force fast delivery. In cells and membranes boyfriend erectile dysfunction young super p-force 160mg otc, ageladine A concentrations are usually unknown and may only be estimated from its concentration used during incubations erectile dysfunction treatment machine cheap 160mg super p-force with amex. Small pH changes are best monitored by excitation at 370 nm and emission at >415 nm or using the Fura 2 filter settings (340/380 exc. The calculation of exact pH values can only be obtained if the dye concentration is known, which is hardly feasible in living cells and tissues. We presently think that only acidic tissues and cells become fluorescent, because ageladine A shows weak or no fluorescence at pH 8 to 9. This is the most critical point, because it is very difficult or nearly impossible to know the exact concentration of the dye at the site of the measurement in living tissue. A major advantage of ageladine A is its emission at 415 to 430 nm where autofluorescence is very low. This considerably increases the signal to noise ratio compared to other pH-sensitive dyes with emissions at longer wavelengths. Potential pitfalls At the moment it is not known whether ageladine A interacts with divalent ions or other molecules to produce false positive results. If it accumulates in cellular membranes, the pH sensitive guanidine moiety should be directed towards the cytosol and track pH changes. It remains to be explored whether some of the guanidine moieties are directed outwards and respond to extracellular pH. In that case, local pH changes close to the membrane may lead to erroneous estimates of bulk changes in pH. The homogenate technique allows for a clear allocation of mean intracellular pH values in tissues to the experimental condition of the animal. It eliminates time delays in pHi assessment associated with other techniques (delays caused by diffusion limitation, delayed equilibration between compartments or the necessity to accumulate recordings to improve the signal to noise ratio). The method follows the freezestop technique, which had been established for determining the metabolite status of shock frozen tissues (Wollenberger et al. Since tissues can be stored away under liquid nitrogen until analysis the method is applicable to samples collected in the field. After completely 152 filling the vial with medium, the mixture is stirred with a needle in order to release air bubbles. In the original procedure the pH of the supernatant is measured using a Radiometer glass capillary pH electrode (G299A). The homogenate technique is the only method that includes the quantitative contribution of all cell and tissue compartments to mean cellular pH and in response to acid-base disturbances, with an emphasis on cytosolic pH (see below). For successful analysis, the resting and experimental states of the tissues must be maintained during invasive sampling. The main merits of the homogenate technique are the simple methodological procedure, low cost, low variability and the small sample size required (as low as 20 mg fresh weight). The method can be used with samples collected from active animals or even from animals collected in the field. The latter is especially relevant in the context of investigations of ocean acidification in situ. The main drawback of the method is that it only allows point measurements as the organism is sacrificed. The use of clean liquid nitrogen and dewars, mortars and pestle free of rime is required. It is usually sufficient to grind on the bottom of a box, for example a Styrofoam box, allowing the evaporating nitrogen to fill up the volume above the mortar and pestle. At the same time, its concentration needs to be minimised since it releases protons during the binding process. Accordingly, the bicarbonate buffer needs to be distinguished from non-bicarbonate buffers (mostly protein and inorganic phosphate). Tissue non-bicarbonate buffer values are best determined using the homogenate technique under metabolic inhibition. This method yields values under control conditions as required for quantitative treatments, i. The intracellular buffer values of tissues are calculated by applying a correction for the dilution of the respective tissue and for extracellular space according to the following equation (Heisler & Neumann, 1980): (F # W); (9. The buffer values of inorganic phosphate is added to this value according to free intracellular concentrations under resting conditions (about! The extracellular space of tissues is determined after incubation in artificial seawater (invertebrates) or in a Ringer solution (fishes) in the presence of 0. The fractional extracellular volume (Q) of the tissue is calculated as the ratio of extracellular tissue water volume and total tissue water volume according to Heisler (1975). Potential pitfalls Regardless of whether buffer values are determined in intact tissue or homogenates, metabolic processes may respond to experimental changes in pH and may interfere with the measurements leading to erroneous pH values or the production of additional buffers during the titration (cf. Hence, the buffer value measured does not actually correspond to any definite physiological state of the tissue, and definitely not to 154 that of control conditions. Complete metabolic inhibition and continuous recording of pH during the titration procedure enable accurate analyses but correction for such metabolic shift is nonetheless required. The calculation is very flexible as the constant can be adjusted to a wide range of ionic compositions, ionic strengths and protein levels in the various compartments. Further experimental, mechanistic, studies are needed to demonstrate the regulatory function of individual acid-base parameters. This will support the development of a cause and effect understanding beyond what can be provided by empirical or correlative analyses. Accordingly, the body fluids of most marine invertebrates display ion compositions similar to those of seawater. In echinoderms, the extracellular fluid is (still) in contact with seawater, indicating that changing the ion composition or the acid-base status of these fluids through ion exchange processes only occurs within narrow limits. The study of extracellular acid-base status requires to consider that acute sampling of body fluids from an animal ("grab and stab") involves disturbance and stress responses, including shifts in the acid-base status, due to changes in metabolic rate, muscular contraction, release of stress hormones etc. It is recommended to implant a permanent optode or a catheter, which is used to withdraw blood after adequate recovery. This is especially important in the more alert fishes, cephalopods and decapod crustaceans. If the "grab and stab" approach cannot be avoided, some species should be anesthetised prior to sampling, using an excessive dose of anaesthetic. The sampling procedure itself, for example through puncturing, needs to be as short and as gentle as possible (for fishes, see for example Welker et al. The results of such procedures must be interpreted with caution and, if possible, cross-calibrated with analyses in cannulated specimens. In general, sampling for blood gas analyses should exclude contamination with air bubbles by use of a gas tight syringe and of cannulas filled with Ringer solution. For small animals, for example small invertebrates or larvae, one can use a glass capillary pulled to a small tip (by use of an electrode puller or by hand above a flame). After puncturing the animal body surface, blood or haemolymph is sucked into the glass by capillary forces. In bivalves, samples of haemolymph have been collected by pericardiac puncture (Fyhn & Costlow, 1975) or from the posterior adductor muscle sinus.
Organizations often find it valuable to have an ongoing relationship with the departing executive-for example impotence def order super p-force 160mg online, by signing a consulting contract that makes the departing executive available as a resource to the new executive for a short time alcohol and erectile dysfunction statistics buy generic super p-force 160 mg line. It Succession Planning and Chief Executive Transition 245 is not advisable to have the departing executive move into a board role or assume a fundraising or programmatic leadership role erectile dysfunction medications causing order 160mg super p-force with visa. Working with Consultants Sometimes the board lacks members with prior experience in hiring executives or in human resources erectile dysfunction lexapro buy super p-force 160 mg lowest price. Appointing an interim or acting chief executive can give the board the breathing space it needs to make a good choice about the permanent executive and ensure that the organization is prepared to work more effectively with that new staff leader. Not every organization in transition will need an interim executive, but a good interim executive can be a powerful partner with the board to build the capacity of the organization during the transition period. Both research and practice demonstrate that groups that employ a skilled interim executive emerge from the transition as stronger organizations. A senior manager or other insider who is appointed to provide bridge management during the interim period, with a temporary salary 246 the Handbook of Nonprofit Governance adjustment. Typically a seasoned executive from outside the organization who, like the acting chief executive, provides bridge leadership during the interim period. An important responsibility of the interim executive is to help prepare the organization to work more effectively with the incoming permanent executive. A good interim executive deals with the day-to-day affairs of the organization, while at the same time building the platform for the permanent successor. As a rule, the interim executive should not be a candidate for the permanent position. An executive from inside or outside the organization who is appointed for an extended period, often twelve to twenty-four months or more. Other options for ensuring bridge leadership for the organization include (1) making no change, based on the assumption that the staff can continue without a chief executive for a limited period; (2) temporary leadership by a board member; or (3) leadership by a management team of senior staff. Typically, the most successful interim executives are mid- to late-career professionals. If, for example, the organization is laboring under an inadequate financial information system, the board may want to look for a temporary executive who has particular strength in that area as well as the capacity to bridge the leadership/management role. Boards should consider hiring an interim executive whose background and demographic profile reflect the community served by the organization. Such an individual can bring cultural competency and important insights to the organization that can help ensure the success of the transition. Successful interim executives tend to be action-oriented but collaborative in their approach, with well-honed listening skills. They help the organization pursue its change agenda, but always in close collaboration with the board and in consultation Succession Planning and Chief Executive Transition 247 with the staff. Boards should ensure that the interim chief executive is available beyond what may be an optimistic timeline. Sometimes a board member will throw a hat into the ring, or the board will actively seek the candidacy of a board member believed to have the time and interest to lead the organization on a temporary basis. But as the board considers what it needs in a temporary executive, familiarity with the organization should not supersede the executive skills needed to manage and lead during a time of transition. A successful search requires the board to always refer back to the goals and vision laid out earlier in the transition process. An organization may never find the "perfect candidate" for the job, but the board should not compromise as it looks for someone with the fundamental skills and qualifications that are required to stabilize the organization and create a successful future. Pre-Search Assessment If the board has been engaged recently (and deeply) in strategic or long-range planning, then transition planning might start with revisiting key elements of the strategic plan and moving directly into a discussion about what skills and characteristics the organization needs in a chief executive in order to accomplish its goals. If a strategic plan is nonexistent or out of date, the transition planning work will have to begin at a more fundamental level. Board and staff leaders can clarify current and future leadership needs by focusing on the following three sets of strategic questions in a series of meetings or a mini-retreat: 1. If there is a gap between our present and our desired future, what kind of leadership will it take to close the gap What does our assessment of where we stand and where we are headed tell us about any pivots or changes the board may need to make Listing the Desired Characteristics At a minimum, the board should sign off on a description of the desired competencies, character, personality, and experience that a new chief executive should have. If the organization has been on a growth trajectory, for example, it may want to look for a chief executive who has experience leading a larger group. In startup organizations, the chief executive is often the founder and keeper of the vision that attracts board members, volunteers, and donors. In a mature organization-one that has had, say, five or more chief executives-the chief executive must sometimes move slowly in changing the vision because so many are now aware of it and believe in it. But he or she must embrace the vision and find new ways for people to relate to it. A board needs a chief executive who can explain, persuade, and empower others to do their best. A few can persuade by the sheer strength of their domineering personalities, although depending on guilt, intimidation, or obligation is typically a short-term leadership style. They go the extra mile, challenging board members, staff, and donors to be above reproach in all areas. Sometimes a law is misunderstood; sometimes a donor tempts one to compromise in return for a gift. But people see the successful chief executive as committed to what is good and honest. When mistakes are uncovered, this type of chief executive is willing to face the music and correct what is wrong. They focus on their strengths to achieve the productivity they enjoy, and they manage their weaknesses-often through delegation. Whether it is a quiet, personal decision following private reflection or a group decision facilitated by the chief executive, the fundamental role of good leaders is to make the call. Startup organizations are often managed by visionaries, who reach their goals by being flexible. As their organizations grow, however, a decision made late-or never made at all-has a negative effect. One way to compensate is to appoint a chief operating officer who makes decisions easily and put him or her in charge of daily operations. Well-organized chief executives know how to manage their schedules to keep family, friends, leisure, and work in balance. They manage their finances well enough to keep themselves and their organizations free from constant money crises. A chief executive who is not well organized needs a solid staff structure as a support and to get the day-to-day tasks accomplished. Nonprofits, too, can improve their bottom line by reaching out to other groups in the independent sector, to businesses, to media corporations, and to government agencies. They need a chief executive with the strategic vision, inventiveness, and diplomatic skills to bring together very different organizations to accomplish a shared goal. If a chief executive is not naturally endowed with high energy, he or she must learn how to generate energy through proper exercise, diet, and rest and how to conserve energy through good planning, wise decision making, and a readiness to delegate. Writing the Position Description Any chief executive is asked to achieve the intended results within the policy parameters set by the board. But candidates will want to see what the board expects the chief executive to accomplish, how the position relates to the board, and what the specific duties are. Identifying Candidates and Narrowing the Field Contacting a broad group of people who know good prospects is the primary way to build a list of potential candidates. An e-mail or letter inviting nominations, Succession Planning and Chief Executive Transition 251 sent to several hundred key constituents and leaders in the field by the board chair or the transition committee chair, is well worth the effort. Often, top candidates are satisfied with their current jobs and are contacted because someone nominated them without their knowledge. Well-placed ads and announcements in print publications and online nonprofit employment sites can also help get the word out. Include a request for a letter of interest, a resume, and the names of references. But even if the transition committee suspects that an internal candidate might be the best choice for chief executive, it should complete all the steps in the search process; an even better candidate might surface along the way. When the announced deadline has passed, the transition committee narrows the field to a short list of three to seven candidates who appear to meet the criteria set early in the process. The transition committee chair or committee members should call these individuals to ask whether they wish to be considered active candidates.
Consumption is small but bio-availability of carotenoids may be greater from fruit than vegetable impotence exercises purchase super p-force 160 mg line, so its contribution to dietary intake and vitamin A status may be higher than the amount in the diet would predict erectile dysfunction vacuum pump order 160 mg super p-force with mastercard. The latter is responsible for the antioxidant properties of the molecule (33 erectile dysfunction herbs generic super p-force 160mg fast delivery, 70 erectile dysfunction ear cheap 160 mg super p-force mastercard, 71). The chemical properties of the carotenoids closely relate to the extended system of conjugated double bonds, which occupies the central part of carotenoid molecules, and various functional groups on the terminal ring structures. Carotenoids in general and lycopene specifically are very efficient at quenching singlet oxygen (72, 73). In this process the carotene absorbs the excess energy from singlet oxygen and then releases it as heat. Singlet oxygen is generated during photosynthesis; therefore, carotenoids are important for protecting plant tissues, but there is limited evidence for this role in humans. It has been suggested that large amounts of dietary carotenes may provide some protection against solar radiation but results are equivocal. Burton and Ingold (33) were the first to draw attention to the radical-trapping properties of -carotene. Using in vitro studies, they showed that -carotene was effective in reducing the rate of lipid peroxidation at the low oxygen concentrations found in tissues. Because all carotenoids have the same basic structure, they should all have similar properties. Indeed, several authors suggest that the hydroxy-carotenoids are better radical-trapping antioxidants than is -carotene (81, 82). It has also been suggested that because the carotenoid molecule is long enough to span the bilayer lipid membrane (83), the presence of oxy functional groups on the ring structures may facilitate similar reactivation of the carotenoid radical in a manner similar to that of the phenoxyl radical of vitamin E (33). Bendich (84) suggested that -carotene protects phagocytes from auto-oxidative damage; enhances T and B lymphocyte proliferative responses; stimulates effector T cell function; and enhances macrophage, cytotoxic T cell, and natural killer cell tumoricidal capacity. Some data are in conflict with evidence of protective effects on the immune system (85, 86) and other data have found no effect (87). Defences may be boosted in those at risk but it may not be possible to demonstrate any benefit in healthy subjects (88). A requirement for antioxidant nutrients Free radicals are a product of tissue metabolism, and the potential damage which they can cause is minimised by the antioxidant capacity and repair mechanisms within the cell. Thus in a metabolically active tissue cell in a healthy subject with an adequate dietary intake, damage to tissue will be minimal and most of the damage occurring will be repaired (36). An important dietary source of antioxidant nutrients is the intake of fruit and vegetables, and it is now well established that persons consuming generous amounts of these foods have a lower risk of chronic disease than do those whose intake is small (15, 16, 89). These observations suggest that the antioxidant nutrient requirements of the general population can be met by a generous consumption of fruit and vegetables and the slogan "5 portions a day" has been promoted to publicize this idea (90). Occasionally, damage may occur which is not repaired and the risk of this happening may increase in the presence of infection or physical trauma. Such effects may exacerbate an established infection or may initiate irreversible changes leading to a state of chronic disease. Can such effects also be minimised by a generous intake of dietary antioxidants in the form of fruit and vegetables or are supplements needed It is generally recognised that certain groups of people have an increased risk of free radical - initiated damage. Premature infants, for example, are at increased risk of oxidative damage because they are born with immature antioxidant status (91-93) and this may be inadequate for coping with high levels of oxygen and light radiation. People who smoke are exposed to free radicals inhaled in the tobacco smoke and have an increased risk of many diseases. People abusing alcohol need to develop increased metabolic capacity to handle the extra alcohol load. Similar risks may be faced by people working in environments where there are elevated levels of volatile solvents. Car drivers and other people working in dense traffic may be exposed to elevated 280 Chapter 17: Dietary antioxidants levels of exhaust fumes. Of the above groups, smokers are the most widely accessible people and this has made them a target for several large antioxidant-nutrient intervention studies. In addition, smokers often display low plasma concentrations of carotenoids and vitamin C. However, no obvious benefits to the health of smokers have emerged from these studies and, in fact, -carotene supplements were associated with an increased risk of lung cancer in two separate studies (35, 94) and with more fatal cardiac events in one of them (95). Other risk groups identified by their already having had some non-malignant form of cancer, such as non-melanomatous skin cancer (77) or a colorectal adenoma (96), showed no effect on subsequent recurrences after several years of elevated intakes of antioxidant nutrients. The use of -carotene (77) or vitamin E alone or in combination with vitamin C (96) showed no benefits. Thus, the results of these clinical trials do not support the use of supplementation with antioxidant micronutrients as a means of reducing cancer or even cardiovascular rates although in the general population, toxicity from such supplements is very unlikely. Some intervention trials however have been more successful in demonstrating a health benefit. Stitch and colleagues (97, 98) gave large quantities of -carotene and sometimes vitamin A to chewers of betel quids in Kerala, India, and to Canadian Inuits with premalignant lesions of the oral tract and showed reductions in leukoplakia and micronuclei from the buccal mucosa. These studies are difficult to interpret because the subjects may have been marginally malnourished at the start and the supplements may have merely restored nutritional adequacy. The mean age of this group was 63 years and obviously they were not a normal adult population, but results of further studies are awaited with keen interest. Lastly, results of the Cambridge Heart Antioxidant Study should be mentioned because they provide some support for a beneficial effect of vitamin E in persons who have had a myocardial infarction (100). Recruits to the study were randomly assigned to receive vitamin E (800 or 400 mg/day) or placebo. Initial results of the trial suggested a significant reduction in nonfatal myocardial infarctions but a non-significant excess of cardiovascular deaths (100). The trial officially ended in 1996, but mortality has continued to be monitored and the authors now report significantly fewer deaths in those who received vitamin E for the full trial (101) (see Chapter 9). In conclusion, some studies have shown that health benefits can be obtained by some people with increased risk of disease from supplements of antioxidant nutrients. The amounts of supplements used have, however, been large and the effect possibly has been pharmacologic. Further work is needed to show whether more modest increases in nutrient intakes in healthy adult populations will delay or prevent the onset of chronic disease. The evidence available regarding health benefits to be achieved by increasing intakes of antioxidant nutrients does not assist in setting nutrient requirements. Proposed definition and plan for review of dietary antioxidant and related compounds. Dietary carcinogens and anticarcinogens, oxygen radicals and degenerative diseases. Update on the biological characteristics of the antioxidant micronutrients: vitamin C, vitamin E and the carotenoids. Dietary antioxdant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Copper and iron are mobilised following myocardial ischemia: Possible predictive criteria for tissue injury. Kinetics of nitric oxide and hydrogen peroxide production and formation of peroxynitrite during the respirtory burst of Human neutrophils. Direct observations of a free radical interaction between vitamin E and vitamin C. Identification of a 57-kilodalton selenoprotein in Human thyrocytes as thioredoxin redctase and evidence that its expression is regulated through the calcium phosphoinositol-signalling pathway. Selenium metabolism and platelet glutathione peroxidase activity in healthy Finnish men: effects of selenium yeast, selenite and selenate. The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. The role of tocopherols in the protection of biological systems against oxidative damage.
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