AKP健食天



阿司匹林、大脑和癌症

Aspirin, brain, and cancer

阿司匹林、大脑和癌症

by Raymond Peat

When a drug such as caffeine or aspirin turns out to have a great variety of protective effects, it's important to understand what it's doing.

当咖啡因或阿司匹林等药物被证明具有各种各样的保护作用时,了解它的作用是很重要的。

Because aspirin has been abused by pharmaceutical companies that have competing products to sell, as well as by the original efforts to promote aspirin itself, people can easily find reasons why they shouldn't take it.

由于有竞争产品出售的制药公司滥用阿司匹林,以及最初推销阿司匹林本身的努力,人们很容易找到不应该服用它的理由。

Early in the 20th century, people were told that fevers were very bad, and that aspirin should be used whenever there is a fever.

In the 1980s, there was a big publicity campaign warning parents that giving aspirin to a child with the flu could cause the potentially deadly Reye syndrome. Aspirin sales declined sharply, as sales of acetaminophen (Tylenol, etc.) increased tremendously. But in Australia, a study of Reye syndrome cases found that six times as many of them had been using acetaminophen as had used aspirin. (Orlowski, et al., 1987)

在20世纪早期,人们被告知发烧是很严重的,只要发烧就应该服用阿司匹林。

在20世纪80年代,曾有一场大规模的宣传活动警告父母,给患流感的孩子服用阿司匹林可能会导致潜在的致命雷氏综合征。阿司匹林的销量急剧下降,而扑热息痛(泰诺等)的销量却大幅增长。但在澳大利亚,一项对雷氏综合征病例的研究发现,使用对乙酰氨基酚的患者是使用阿司匹林的6倍。(Orlowski等,1987)

Until the 1950s and 1960s, when new products were being promoted, little was said about the possibility of stomach ulceration from aspirin. Lately, there has been more publicity about the damage it can do to the stomach and intestine, much of it in connection with the sale of the new "COX-2 inhibitors." (These new drugs, rather than protecting the circulatory system as aspirin does, damage it.) Aspirin rapidly breaks down into acetic acid and salicylic acid (which is found in many fruits), and salicylic acid is protective to the stomach and intestine, and other organs. When aspirin was compared with the other common antiinflammatory drugs, it was found that the salicylic acid it releases protects against the damage done by another drug. (Takeuchi, et al, 2001; Ligumsky, et al., 1985.) Repeated use of aspirin protects the stomach against very strong irritants. The experiments in which aspirin produces stomach ulcers are designed to produce ulcers, not to realistically model the way aspirin is used.

直到20世纪50年代和60年代,当新产品被推广时,很少有人说阿司匹林可能导致胃溃疡。最近,关于它对胃和肠的损害有了更多的宣传,这在很大程度上与新型“COX-2抑制剂”的销售有关。(这些新药不像阿司匹林那样保护循环系统,而是破坏循环系统。)阿司匹林能迅速分解成醋酸和水杨酸(许多水果中都有),水杨酸对胃、肠和其他器官有保护作用。当将阿司匹林与其他常见的抗炎药物进行比较时,人们发现它释放的水杨酸可以保护阿司匹林免受其他药物造成的损害。(Takeuchi等,2001;Ligumsky等人,1985年。)反复服用阿司匹林可以保护胃不受强烈的刺激。阿司匹林产生胃溃疡的实验是为了产生溃疡而设计的,而不是真实地模拟阿司匹林的使用方式。

Recently, the public has been led to believe that drugs are being designed to fit certain cellular "receptors." The history of the "COX-2 inhibitors" is instructive, in a perverse way. The structures of DES and other synthetic estrogens were said to relate to "the estrogen receptor." Making these estrogenic molecules more soluble in water made them somewhat anti-estrogenic, leading to products such as Tamoxifen. But some of the molecules in this group were found to be antiinflammatory. The structure of Celecoxib and other "COX-2 inhibitors" is remarkably similar to the "designer estrogens." Considering this, it's a little odd that so few in the U.S. are openly discussing the possibility that estrogen's function is directly related to inflammation, and involves the production of many inflammatory mediators, including COX-2. (See Lerner, et al., 1975; Luo, et al., 2001; Cushman, et al, 2001; Wu, et al., 2000; Herrington, et al., 2001.)

最近,公众开始相信药物是为了适应特定的细胞“受体”而设计的。“COX-2抑制剂”的历史以一种反常的方式具有指导意义。DES和其他合成雌激素的结构据说与“雌激素受体”有关。使这些雌激素分子更容易溶于水,使它们具有抗雌激素作用,从而产生了它莫西芬(Tamoxifen)等产品。但这一组中的一些分子被发现是抗炎的。塞来昔布和其他COX-2抑制剂的结构与“设计雌激素”非常相似。考虑到这一点,有点奇怪的是,在美国很少有人公开讨论雌激素的功能与炎症直接相关的可能性,并涉及许多炎症介质的产生,包括COX-2。

Soot and smoke contain many chemicals that produce inflammation (Brune, et al., 1978). In the 1930s, soot was known to be both carcinogenic and estrogenic, and analysis of its components led to the production of the early commercial estrogens. Any intelligent person reading the chemical and biological publications of that time will see how closely associated cancer, inflammation, and estrogen are.

煤烟和烟雾含有许多能引起炎症的化学物质(Brune等,1978年)。在20世纪30年代,烟灰被认为是致癌物质和雌激素,对其成分的分析导致了早期商业雌激素的生产。任何一个聪明的人,只要阅读了当时的化学和生物出版物,就会发现癌症、炎症和雌激素之间的联系是多么紧密。

Soon after vitamin E was discovered, tocopherol was defined as a brain-protective, pregnancy protective, male fertility protective, antithrombotic, antiestrogenic agent. But very soon, the estrogen industry made it impossible to present ideas that explained vitamin E, progesterone, vitamin A, or thyroid hormone in terms of the protection they provide against estrogenic substances. Since the polyunsaturated fats caused the same conditions that were caused by unopposed estrogen, vitamin E came to be known as an "antioxidant," because it reduced their toxicity. (Vitamin E is now known to suppress COX-2, synergizing with aspirin and opposing estrogen.)

维生素E被发现后不久,生育酚就被定义为一种保护大脑,怀孕保护,男性生育保护,抗血栓,抗雌激素的药物。但很快,雌激素产业就无法解释维生素E,黄体酮,维生素A或甲状腺激素对雌激素物质的保护作用。由于多不饱和脂肪引起的情况与雌激素引起的情况相同,维生素E被称为“抗氧化剂”,因为它降低了它们的毒性。(现在已知维生素E能抑制COX-2,与阿司匹林协同作用,对抗雌激素。)

In 1970, when I was beginning to see the ways in which unopposed estrogen and accumulated polyunsaturated fats interacted with a vitamin E deficiency during aging and in infertility, I got some prostaglandins to experiment with, since they are products of the oxidation of linoleic acid. The prostaglandins are an interesting link between estrogens and inflammation, in normal physiology as well as in disease.

1970年,当我开始发现在衰老和不孕症过程中,非对抗雌激素和积累的多不饱和脂肪与维生素E缺乏相互作用的方式时,我得到了一些前列腺素来做实验,因为它们是亚油酸氧化的产物。前列腺素是雌激素和炎症之间有趣的联系,在正常生理和疾病中都是如此。

I wanted to test their effects on the uterus, especially the sites where the embryos implant. There was a theory that the electrical charge of the surface of the uterus was decreased at the implantation sites, to reduce the repulsion between two negatively charged things. Although there were regions of lower surface charge along the lining of the uterus, the charge changed as waves of muscle contraction moved along the uterus, and the prostaglandins affected the contractions.

我想测试它们对子宫的影响,尤其是胚胎植入的部位。有一种理论认为子宫表面的电荷在着床处减少,以减少两个带负电荷的物体之间的排斥。虽然子宫内膜有较低表面电荷区,但电荷随肌肉收缩波沿子宫移动而改变,前列腺素影响收缩。

To understand the differences between the different types of prostaglandin, I tested them on my arm, and those with the most hydroxyl groups produced regions with an increased negative charge. For comparison, I exposed another spot to sunlight for an hour, and found that there was a similar increase in the negative charge in that spot. Apparently the prostaglandins were causing an injury or excitation, a mild inflammation, in the skin cells.

为了了解不同类型的前列腺素之间的区别,我在我的手臂上测试了它们,那些羟基最多的会产生负电荷增加的区域。作为比较,我把另一个点暴露在阳光下一小时,发现在那个点有类似的负电荷增加。显然,前列腺素引起了皮肤细胞的损伤或兴奋,一种轻微的炎症。

A few years later, aspirin was found to inactivate the enzyme that forms prostaglandins, by the transfer of the acetyl radical to the enzyme. This became the orthodox "explanation" for what aspirin does, though it neglected to explain that salicylic acid (lacking the acetyl radical) had been widely known in the previous century for its very useful antiinflammatory actions. The new theory did explain (at least to the satisfaction of editors of medical magazines) one of aspirin's effects, but it distracted attention from all the other effects of aspirin and salicylic acid.

几年后,人们发现阿司匹林通过将乙酰基转移到酶上而使形成前列腺素的酶失活。这成为阿司匹林作用的正统“解释”,尽管它忽视了水杨酸(缺乏乙酰基)在上个世纪因其非常有用的抗炎作用而广为人知。这个新理论确实解释了(至少让医学杂志的编辑满意)阿司匹林的一种作用,但它分散了人们对阿司匹林和水杨酸的其他作用的注意力。

Aspirin is an antioxidant that protects against lipid peroxidation, but it also stimulates mitochondrial respiration. It can inhibit abnormal cell division, but promote normal cell division. It can facilitate learning, while preventing excitotoxic nerve injury. It reduces clotting, but it can decrease excessive menstrual bleeding. These, and many other strangely beneficial effects of aspirin, strongly suggest that it is acting on very basic biological processes, in a coherent way.

阿司匹林是一种抗氧化剂,可以防止脂质过氧化,但它也能刺激线粒体呼吸。它能抑制异常细胞分裂,但能促进正常细胞分裂。它可以促进学习,同时防止兴奋毒性神经损伤。它可以减少凝血,但可以减少月经过多出血。这些,以及阿司匹林的许多其他奇怪的有益作用,强烈地表明它以一种连贯的方式,在非常基本的生物过程中起作用。

In explaining aspirin's effects, as in explaining those of estrogen and progesterone, or polyunsaturated fats and vitamin E, I think we need concepts of a very broad sort, such as "stability and instability."

The COX (cyclooxygenase) enzymes, that make prostaglandins, are just one system among many that are activated by stress. Aromatase, that makes estrogen, enzymes that make histamine, serotonin and nitric oxide, the cytokines, and the stress-induced hormones of the pituitary and adrenal glands, are turned on in difficult situations, and have to be turned off when the threat has been overcome. The production of energy is the basis for overcoming all threats, and it has to be conserved in readiness for future needs.

在解释阿司匹林的作用时,就像解释雌激素和黄体酮,或多不饱和脂肪和维生素E的作用一样,我认为我们需要一个非常宽泛的概念,比如“稳定性和不稳定性”。

制造前列腺素的COX(环氧合酶)酶只是许多被压力激活的系统中的一个。制造雌激素的芳香化酶、制造组胺、血清素和一氧化氮的酶、细胞因子以及垂体和肾上腺的应激激素的酶,在困难的情况下会启动,当威胁被克服时就必须关闭。能源的生产是克服所有威胁的基础,必须加以保护,以便为将来的需要做好准备。

The fetus produces saturated fats such as palmitic acid, and the monounsaturated fat, oleic acid, which can be turned into the Mead acid, ETrA (5,8,11-eicosatrienoic acid), and its derivatives, which are antiinflammatory, and some of which act on the "bliss receptor," or the cannibinoid receptor. In the adult, tissues such as cartilage, which are protected by their structure or composition from the entry of exogenous fats, contain the Mead acid despite the presence of linoleic acid in the blood.

胎儿产生棕榈酸等饱和脂肪和不饱和脂肪,油酸,可以变成了米德酸,ETrA (5 8 11-一种叫二十碳三烯酸的pufa)及其衍生物,抗炎,和其中的一些行为上的“幸福受体”或大麻素受体。在成人中,尽管血液中存在亚油酸,但软骨等组织仍含有米德酸,这些组织的结构或组成受到外源性脂肪的保护。

At birth, the baby's mitochondria contain a phospholipid, cardiolipin, containing palmitic acid, but as the baby eats foods containing polyunsaturated fatty acids, the palmitic acid in cardiolipin is replaced by the unsaturated fats. As the cardiolipin becomes more unsaturated, it becomes less stable, and less able to support the activity of the crucial respiratory enzyme, cytochrome oxidase.

The respiratory activity of the mitochondria declines as the polyunsaturated oils replace palmitic acid, and this change corresponds to the life-long decline of the person's metabolic rate.

In old age, a person's life expectancy strongly depends on the amount of oxygen that can be used. When the mitochondria can't use oxygen vigorously, cells must depend on inefficient glycolysis for their energy.

出生时,婴儿的线粒体中含有一种磷脂,即心磷脂,它含有软脂酸,但随着婴儿食用含有多不饱和脂肪酸的食物,心磷脂中的软脂酸被不饱和脂肪所取代。当心磷脂变得更加不饱和时,它就变得不稳定,并且不能支持至关重要的呼吸酶——细胞色素氧化酶的活动。

线粒体的呼吸活动随着多不饱和油脂取代棕榈酸而下降,这种变化与人代谢率的终生下降相对应。

在老年,一个人的寿命很大程度上取决于可用的氧气量。当线粒体不能充分利用氧气时,细胞必须依赖低效的糖酵解来获取能量。

Estrogen activates the glycolytic pathway, while interfering with mitochondrial respiration. This resembles the aged or stressed metabolism, in which lactic acid is produced instead of carbon dioxide.

雌激素激活糖酵解途径,同时干扰线粒体呼吸。这类似于衰老或压力代谢,在此过程中产生的是乳酸而不是二氧化碳。

Aspirin activates both glycolysis and mitochondrial respiration, and this means that it shifts the mitochondria away from the oxidation of fats, toward the oxidation of glucose, resulting in the increased production of carbon dioxide. Its action on the glycolytic enzyme, GAPDH, is the opposite of estrogen's.

阿司匹林同时激活糖酵解和线粒体呼吸,这意味着它将线粒体从脂肪的氧化转移到葡萄糖的氧化,从而增加二氧化碳的产生。它对糖酵解酶GAPDH的作用与雌激素相反。

The shift away from fat oxidation under the influence of aspirin doesn't lead to an accumulation of free fatty acids in the circulation, since aspirin inhibits the release of fatty acids from both phospholipids and triglycerides. Estrogen has the opposite effects, increasing fat oxidation while increasing the level of circulating free fatty acids, since it activates lipolysis, as do several other stress-related hormones.

由于阿司匹林抑制了磷脂和甘油三酯中脂肪酸的释放,在阿司匹林的影响下,脂肪氧化的转变不会导致循环中自由脂肪酸的积累。雌激素有相反的作用,在增加循环中的游离脂肪酸水平的同时,也增加了脂肪的氧化,因为它和其他一些与压力相关的激素一样,会激活脂肪分解。

The polyunsaturated fatty acids, such as linolenic, linoleic, arachidonic, EPA, and DHA, have many directly toxic, antirespiratory actions, apart from the production of the prostaglandins or eicosanoids. Just by preventing the release of these fatty acids, aspirin would have broadly antiinflammatory effects.

多不饱和脂肪酸,如亚麻酸、亚油酸、花生四烯酸、EPA和DHA,除了产生前列腺素或二十烷酸外,还有许多直接的毒性和抗呼吸作用。仅仅通过阻止这些脂肪酸的释放,阿司匹林就有广泛的抗炎作用。

Since the polyunsaturated fats and prostaglandins stimulate the expression of aromatase, the enzyme that synthesizes estrogen, aspirin decreases the production of estrogen. So many of aspirin's effects oppose those of estrogen, it would be tempting to suggest that its "basic action" is the suppression of estrogen. But I think it's more likely that both estrogen and aspirin are acting on some basic processes, in approximately opposite ways.

由于多不饱和脂肪和前列腺素刺激合成雌激素的芳香化酶的表达,阿司匹林减少了雌激素的产生。阿司匹林的许多作用与雌激素的作用相反,因此人们很容易认为它的“基本作用”是抑制雌激素。但我认为更有可能的是雌激素和阿司匹林都在一些基本的过程中起作用,以几乎相反的方式。

Bioelectrical functions, and the opposition between carbon dioxide and lactic acid, and the way water is handled in cells, are basic conditions that have a general or global effect on all of the other more specific biochemical and physiological processes. Originally, estrogen and progesterone were each thought to affect only one or a few biochemical events, but it has turned out that each has a multitude of different biochemical actions, which are integrated in globally meaningful ways. The salicylic acid molecule is much smaller and simpler than progesterone, but the range of its beneficial effects is similar. Because of aspirin's medical antiquity, there has been no inclination to explain its actions in terms of an "aspirin receptor," as for valium and the opiates, leaving its biochemistry, except for the inadequate idea of COX-inhibition, simply unexplained.

生物电功能,二氧化碳和乳酸之间的对立,以及水在细胞中的处理方式,都是基本条件,对所有其他更具体的生化和生理过程具有普遍或全面的影响。最初,雌激素和黄体酮都被认为只影响一个或几个生化事件,但事实证明,它们都有大量不同的生化作用,并以具有全球意义的方式整合在一起。水杨酸分子比孕酮小得多,也简单得多,但其有益作用的范围是相似的。由于阿司匹林在医学上的古老,没有倾向于用“阿司匹林受体”来解释它的作用,至于安定和阿片类药物,这使得它的生物化学,除了cox抑制的不充分的想法,根本无法解释。

If we didn't eat linoleic acid and the other so-called "essential fatty acids," we would produce large amounts of the "Mead acid," n-9 eicosatrienoic acid, and its derivatives. This acid in itself is antiinflammatory, and its derivatives have a variety of antistress actions. The universal toxicity of the polyunsaturated fats that suppress the Mead fats as they accumulate, and the remarkable vitality of the animals that live on a diet deficient in the essential fatty acids, indicate that the Mead fats are important factors in the stability of our mammalian tissues. This protective lipid system probably interacts with cellular proteins, modifying the way they bind water and carbon dioxide and ions, affecting their electrons and their chemical reactivity.

如果我们不吃亚油酸和其他所谓的“必需脂肪酸”,我们就会产生大量的“米德酸”,n-9二十碳三烯酸及其衍生物。这种酸本身是抗炎的,它的衍生物有多种抗应激作用。多不饱和脂肪的普遍毒性抑制了Mead脂肪的积累,以及在缺乏必需脂肪酸的饮食中生活的动物的显著活力,表明Mead脂肪是我们哺乳动物组织稳定的重要因素。这种保护脂质系统可能与细胞蛋白质相互作用,改变它们与水、二氧化碳和离子结合的方式,影响它们的电子和化学反应性。

If salicylic acid and the structurally similar antiinflammatories, local anesthetics, muscle relaxants, expectorants, and antihistamines, act as surrogates for the absent Mead acid family, and thereby act as defenses against all the toxic effects of the unstable fats, it would explain the breadth and apparent coherence of their usefulness. And at the same time it explains some of the ways that estrogen goes out of control, when it exacerbates the toxicity of the accumulated unstable fats.

如果水杨酸和结构类似的抗炎,局部麻醉剂,肌肉松弛剂,祛痰剂,抗组胺药,充当代孕母亲的缺席米德酸家庭,从而作为防御的毒性作用不稳定的脂肪,它可以解释其效用的广度和明显的一致性。同时,它解释了雌激素失控的一些方式,当它加剧累积的不稳定脂肪的毒性时。

The competition between aspirin and salicylic acid, and other antiinflammatories, for the active site on the COX enzyme (Rao, et al., 1982), shows that the structural features of these molecules are in some ways analogous to those of the polyunsaturated fatty acids. Wherever there are phospholipids, free fatty acids, fatty acid esters, ethers, etc. (i.e., in mitochondria, chromosomes, cytoskeleton, collagen networks--essentially everywhere in and around the cell), the regulatory influence of specific fatty acids--or their surrogates--will be felt.

阿司匹林和水杨酸以及其他抗炎药对COX酶活性位点的竞争(Rao等人,1982)表明,这些分子的结构特征在某些方面类似于多不饱和脂肪酸。只要有磷脂、游离脂肪酸、脂肪酸酯、醚等(例如,在线粒体、染色体、细胞骨架、胶原蛋白网络中——基本上在细胞内部和周围的任何地方),就会感受到特定脂肪酸或它们的替代品的调节影响。

Although it would undoubtedly be best to grow up eating foods with relatively saturated fats, the use of aspirin preventively and therapeutically seems very reasonable under the present circumstances, in which, for example, clean and well ripened fruits are not generally available in abundance. Preventing blindness, degenerative brain diseases, heart and lung diseases, and cancer with aspirin should get as much support as the crazy public health recommendations are now getting from government and foundations and the medical businesses.

尽管在成长过程中食用相对饱和脂肪的食物无疑是最好的,但在目前的情况下,预防和治疗方面使用阿司匹林似乎是非常合理的,例如,清洁和成熟的水果通常不是很多。用阿司匹林预防失明、退化性脑疾病、心肺疾病和癌症应该得到和政府、基金会和医疗企业疯狂的公共健康建议一样多的支持。

When people with cancer ask for my recommendations, they usually think I'm joking when I tell them to use aspirin, and very often they don't take it, on the basis of what seems to be a very strong cultural prejudice. Several years ago, a woman whose doctors said it would be impossible to operate on her extremely painful "inflammatory breast cancer," had overnight complete relief of the pain and swelling from taking a few aspirins. The recognized anti-metastatic effect of aspirin, and its ability to inhibit the development of new blood vessels that would support the tumor's growth, make it an appropriate drug to use for pain control, even if it doesn't shrink the tumor. In studies of many kinds of tumor, though, it does cause regression, or at least slows tumor growth. And it protects against many of the systemic consequences of cancer, including wasting (cachexia), immunosuppression, and strokes.

当癌症患者询问我的建议时,当我告诉他们使用阿司匹林时,他们通常认为我在开玩笑,他们通常不服用,这似乎是基于一种非常强烈的文化偏见。几年前,一名妇女因服用几片阿斯匹林,一夜之间疼痛和肿胀完全缓解,医生说她的“炎性乳腺癌”极其痛苦,不可能动手术。公认的阿司匹林的抗转移作用,以及它抑制支持肿瘤生长的新血管的生长的能力,使它成为一种用于控制疼痛的合适药物,即使它不能使肿瘤缩小。然而,在对多种肿瘤的研究中,它确实会导致衰退,或至少减缓肿瘤的生长。它还能预防癌症的许多系统性后果,包括消瘦(恶病质)、免疫抑制和中风。

Opiates are the standard medical prescription for pain control in cancer, but they are usually prescribed in inadequate quantities, "to prevent addiction." Biologically, they are the most inappropriate means of pain control, since they increase the release of histamine, which synergizes with the tumor-derived factors to suppress immunity and stimulate tumor growth.

It has recently become standard practice in most places to advise a person who is having a heart attack to immediately chew and swallow an aspirin tablet.

阿片类药物是控制癌症患者疼痛的标准医疗处方,但通常处方数量不足,“以防止上瘾”。生物学上,它们是最不合适的疼痛控制手段,因为它们增加了组胺的释放,而组胺与肿瘤衍生因子协同抑制免疫和刺激肿瘤生长。

最近,在大多数地方,建议心脏病发作的人立即咀嚼并吞下一片阿司匹林片已成为标准做法。

The same better-late-than-never philosophy can be applied to Alzheimer's disease, Parkinson's disease, and other degenerative nerve diseases. Aspirin protects against several kinds of toxicity, including excitotoxicity (glutamate), dopamine toxicity, and oxidative free radical toxicity. Since its effects on the mitochondria are similar to those of thyroid (T3), using both of them might improve brain energy production more than just thyroid. (By activating T3, aspirin can sometimes increase the temperature and pulse rate.) Magnesium, niacinamide, and other nerve protective substances work together.

同样的“晚到总比不到好”的理论也适用于阿尔茨海默病、帕金森病和其他神经退行性疾病。阿司匹林可以抵抗多种毒性,包括兴奋性毒性(谷氨酸)、多巴胺毒性和氧化性自由基毒性。由于它对线粒体的影响与甲状腺(T3)相似,使用两者可能比仅仅使用甲状腺更能提高大脑能量生产。(通过激活T3,阿司匹林有时会增加体温和脉搏。)镁、烟酰胺和其他神经保护物质共同作用。

In multiple organ failure, which can be caused by profound shock caused by trauma, infection, or other stress, aspirin is often helpful, but carbon dioxide and hypertonic glucose and sodium are more important.

在由创伤、感染或其他压力引起的严重休克引起的多器官衰竭中,阿司匹林通常是有帮助的,但二氧化碳、高渗葡萄糖和钠更重要。

Aspirin, like progesterone or vitamin E, can improve fertility, by suppressing a prostaglandin, and improving uterine circulation.

Although the animal studies that showed stomach damage from aspirin often used single doses equivalent to 10 or 100 aspirin tablets, the slight irritation produced by a normal dose of aspirin can be minimized by dissolving the aspirin in water. The stomach develops a tolerance for aspirin over a period of a few days, allowing the dose to be increased if necessary. And both aspirin and salicylic acid can be absorbed through the skin, so rheumatic problems have been treated by adding the drug to bath water.

阿司匹林,像孕酮或维生素E一样,可以通过抑制前列腺素和改善子宫循环来提高生育能力。

虽然动物研究表明阿司匹林对胃的损害通常是使用相当于10或100片阿司匹林片的单剂量,但通过将阿司匹林溶解在水中,可以将正常剂量阿司匹林产生的轻微刺激降到最低。胃会在几天内对阿司匹林产生耐受性,必要时可以增加剂量。阿司匹林和水杨酸都可以被皮肤吸收,所以风湿病的治疗方法是在洗澡水中加入这种药物。

The unsaturated (n-6 and n-3) fats that accumulate in our tissues, instead of being part of the system for reestablishing order and stability, tend to amplify the instability that is triggered by excitation, by estrogen, or by external stresses.

不饱和脂肪(n-6和n-3)在我们的组织中积累,而不是重建秩序和稳定的系统的一部分,倾向于放大由兴奋、雌激素或外部压力触发的不稳定性。

I think it's important that we don't allow the drug publicists to obscure the broad importance of substances such as aspirin, vitamin E, progesterone, and thyroid. For 60 years, a myth that was created to sell estrogen has harmed both science and the health of many people.

我认为重要的是,我们不允许药品宣传人员掩盖阿司匹林、维生素E、孕酮和甲状腺等物质的广泛重要性。60年来,一个为推销雌激素而创造的神话损害了科学和许多人的健康。

REFERENCES

Free Radic Biol Med 2000 Dec 1;29(11):1135-42. Synergistic inhibition of cyclooxygenase-2 expression by vitamin E and aspirin. Abate A, Yang G, Dennery PA, Oberle S, Schroder H

Proc Natl Acad Sci U S A 1995 Aug 15;92(17):7926-30. The mode of action of aspirin-like drugs: effect on inducible nitric oxide synthase. Amin AR, Vyas P, Attur M, Leszczynska-Piziak J, Patel IR, Weissmann G, Abramson SB. "These studies indicate that the inhibition of iNOS expression and function represents another mechanism of action for aspirin, if not for all aspirin-like drugs."

Obstet Gynecol 2001 Mar;97(3):423-7. Aspirin effects on endometrial cancer cell growth.Arango HA, Icely S, Roberts WS, Cavanagh D, Becker JL

J Neurochem 2001 Mar;76(6):1895-904. Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. Asanuma M, Nishibayashi-Asanuma S, Miyazaki I, Kohno M, Ogawa N.

J Neurochem 1998 Oct;71(4):1635-42. Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice. Aubin N, Curet O, Deffois A, Carter C.

Psychopharmacology (Berl) 1998 Aug;138(3-4):369-74. The influence of acetylsalicylic acid on cognitive processing: an event-related potentials study. Austermann M, Grotemeyer KH, Evers S, Rodding D, Husstedt IW

Brain Res 1999 Oct 2; 843(1-2): 118-29. Cyclooxygenase-2 selective inhibitors aggravate kainic acid induced seizure and neuronal cell death in the hippocampus. Baik EJ, Kim EJ, Lee SH, Moon C

Cancer Lett 1978 Jun;4(6):333-42. Inflammatory, tumor initiating and promoting activities of polycyclic aromatic hydrocarbons and diterpene esters in mouse skin as compared with their prostaglandin releasing potency in vitro. Brune K, Kalin H, Schmidt R, Hecker E.

J Neurooncol 2000;46(3):215-29. Acetaminophen selectively reduces glioma cell growth and increases radiosensitivity in culture. Casper D, Lekhraj R, Yaparpalvi US, Pidel A, Jaggernauth WA, Werner P, Tribius S, Rowe JD, LaSala PA "Glioblastoma multiforme (GBM) is a highly lethal brain cancer. Using cultures of rodent and human malignant glioma cell lines, we demonstrated that millimolar concentrations of acetylsalicylate, acetaminophen, and ibuprofen all significantly reduce cell numbers after several days of culture."

Neurosci Lett 2000 Aug 11;289(3):201-4. Ibuprofen protects dopaminergic neurons against glutamate toxicity in vitro. Casper D, Yaparpalvi U, Rempel N, Werner P. "We examined the effects of aspirin, acetaminophen, and ibuprofen on cultured primary rat embryonic neurons from mesencephalon, the area primarily affected in Parkinson's disease. We evaluated whether these drugs protect dopaminergic neurons against excitotoxicity. All three NSAIDs significantly attenuated the decrease in dopamine uptake caused by glutamate, indicating preservation of neuronal integrity."

Lipids 1996 Aug;31(8):829-37. Effect of dietary n-9 eicosatrienoic acid on the fatty acid composition of plasma lipid fractions and tissue phospholipids. Cleland LG, Neumann MA, Gibson RA, Hamazaki T, Akimoto K, James MJ "Dietary enrichment with ETrA warrants further investigation for possible beneficial effects in models of inflammation and autoimmunity, as well as in other conditions in which mediators derived from n-6 fatty acids can affect homeostasis adversely."

Can J Ophthalmol 1981 Jul;16(3):113-8. Senile cataracts: evidence for acceleration by diabetes and deceleration by salicylate. Cotlier E.

Int Ophthalmol 1981 May;3(3):173-7. Aspirin effect on cataract formation in patients with rheumatoid arthritis alone or combined with diabetes. Cotlier E. "The effects of aspirin on cataract formation may result from 1) lowering of plasma tryptophan levels and increased excretion of tryptophan metabolites, 2) inhibition of aldose reductase and sorbitol formation in the diabetic lens, 3) inhibition of tryptophan or kynurenine binding to lens protein."

Arterioscler Thromb Vasc Biol 2001 Feb;21(2):255-61. Tamoxifen and cardiac risk factorsin healthy women: Suggestion of an anti-inflammatory effect. Cushman M, Costantino JP, Tracy RP, Song K, Buckley L, Roberts JD, Krag DN.

Med Sci Sports Exerc 2001 Dec;33(12):2029-35. Acetylsalicylic acid inhibits the pituitary response to exercise-related stress in humans. Di Luigi L, Guidetti L, Romanelli F, Baldari C, Conte D.

Ann Med 2000 Dec;32 Suppl 1:21-6. Cyclo-oxygenase products and atherothrombosis.FitzGerald GA, Austin S, Egan K, Cheng Y, Pratico D

Acta Diabetol Lat 1981;18(1):27-36. Effects of acetylsalicylic acid on plasma glucose, free fatty acid, betahydroxybutyrate, glucagon and C-peptide responses to salbutamol in insulin-dependent diabetic subjects. Giugliano D, Passariello N, Torella R, Cerciello T, Varricchio M, Sgambato S.

J Reprod Fertil 1994 Aug;101(3):523-9. Relationships among GnRH, substance P, prostaglandins, sex steroids and aromatase activity in the brain of the male lizard Podarcis sicula sicula during reproduction. Gobbetti A, Zerani M, Di Fiore MM, Botte V "Acetylsalicylic acid decreased PGF2 alpha, oestradiol and aromatase activity, but increased the amount of androgens released."

Natl Med J India 1998 Jan-Feb;11(1):14-7. Aspirin: a neuroprotective agent at high doses? Gomes I.

Radiat Res 1991 Sep;127(3):317-24. Effects of some nonsteroidal anti-inflammatory agents on experimental radiation pneumonitis. Gross NJ, Holloway NO, Narine KR.

Micron 2001 Apr;32(3):307-15. Collagen as a model system to investigate the use of aspirin as an inhibitor of protein glycation and crosslinking. Hadley J, Malik N, Meek K.

J Pharmacol Exp Ther 1981 Aug;218(2):464-9. Protective effects of aspirin in endotoxic shock. Halushka PV, Wise WC, Cook JA.

J Pharmacol Exp Ther 2000 May; 293(2):417-25. Cyclooxygenase-2 contributes to N-methyl-D-aspartate-mediated neuronal cell death in primary cortical cell culture.Hewett SJ, Uliasz TF, Vidwans AS, Hewett JA

Med Hypotheses 1999 Apr;52(4):291-2. Genetic induction and upregulation of cyclooxygenase (COX) and aromatase (CYP19): an extension of the dietary fat hypothesis of breast cancer. Harris RE, Robertson FM, Abou-Issa HM, Farrar WB, Brueggemeier R A novel model of mammary carcinogenesis is proposed involving sequential induction and upregulation of cyclooxygenase and aromatase genes by essential fatty acids prominent in the US diet.

J Clin Endocrinol Metab 2001 Sep; 86(9):4216-22. Differential effects of E and droloxifene on C-reactive protein and other markers of inflammation in healthy postmenopausal women. Herrington DM, Brosnihan KB, Pusser BE, Seely EW, Ridker PM, Rifai N, MacLean DB. "E treatment resulted in 65.8% higher levels of C-reactive protein (P = 0.0002) and 48.1% higher levels of IL-6...." "These data provide additional evidence of a proinflammatory effect of E that may have adverse cardiovascular consequences."

J Natl Cancer Inst 1998 Mar 18;90(6):455-60. Expression of cyclooxygenase-1 and cyclooxygenase-2 in human breast cancer. Hwang D, Scollard D, Byrne J, Levine E "Our results suggest that overexpression of COX may not be unique to colon cancer and may be a feature common to other epithelial tumors."

Ginekol Pol 1999 Mar;70(3):126-34. [Evaluation of the effectiveness of a low-dose aspirin in the treatment of intrauterine growth retardation (IUGR)]. Kalinka J, Sieroszewski P, Hanke W, Laudanski T, Suzin J

J Cardiovasc Pharmacol 1995 Feb;25(2):273-81. Inhibitory effects of aspirin on coronary hyperreactivity to autacoids after arterial balloon injury in miniature pigs. Kuga T, Ohara Y, Shimokawa H, Ibayashi S, Tomoike H, Takeshita A. "Coronary vasoconstriction induced by histamine and serotonin were examined angiographically before, 1 h, 1 week, and 1 month after balloon injury in 29 hypercholesterolemic miniature pigs." "Hyperconstriction induced by the autacoids 1 h after injury were significantly less in groups B and C than in group A (p < 0.01). Hyperconstriction induced by autacoids 1 week after injury were significantly less in group B than in group A (p < 0.01) and were significantly less in group C than in group A (p < 0.01) or group B (p < 0.05)."

Proc Soc Exp Biol Med 1975 Feb;148(2):329-32. Correlation of anti-inflammatory activity with inhibition of prostaglandin synthesis activity of nonsteroidal anti-estrogens and estrogens (38532). Lerner EJ, Carminati P, Schiatti P.

Proc Soc Exp Biol Med 1985 Feb;178(2):250-3. Salicylic acid blocks indomethacin-induced cyclooxygenase inhibition and lesion formation in rat gastric mucosa.Ligumsky M, Guth PH, Elashoff J, Kauffman GL Jr, Hansen D, Paulsen G. "Salicylic acid has been shown to decrease gastric mucosal lesions induced by indomethacin in the rat."

Z Naturforsch [C] 2001 May-Jun; 56(5-6):455-63. Constant expression of cyclooxygenase-2 gene in prostate and the lower urinary tract of estrogen-treated male rats. Luo C, Strauss L, Ristimaki A, Streng T, Santti R.

Neuropharmacology 2000 Apr 27;39(7):1309-18. Mechanisms of the neuroprotective effect of aspirin after oxygen and glucose deprivation in rat forebrain slices. Moro MA, De Alba J, Cardenas A, De Cristobal J, Leza JC, Lizasoain I, Diaz-Guerra MJ, Bosca L, Lorenzo P "Apart from its preventive actions against stroke due to its antithrombotic properties, recent data in the literature suggest that high concentrations of ASA also exert direct neuroprotective effects." "We have found that ASA inhibits neuronal damage at concentrations lower than those previously reported (0.1-0.5 mM), and that these effects correlate with the inhibition of excitatory amino acid release, of NF-kappaB translocation to the nucleus and iNOS expression caused by ASA." "Our results also show that the effects of ASA are independent of COX inhibition. Taken together, our present findings show that ASA is neuroprotective in an in vitro model of brain ischaemia at doses close to those recommended for its antithrombotic effects."

Pediatrics 1987 Nov;80(5):638-42. A catch in the Reye. Orlowski JP, Gillis J, Kilham HA.

Prostaglandins Leukot Med 1982 Jul;9(1):109-15. Effect of acetaminophen and salicylate on aspirin-induced inhibition of human platelet cyclo-oxygenase. Rao GH, Reddy KR, White JG. "Recent studies have shown that salicylic acid, a metabolite of aspirin, effectively competes for the same site on the platelet cyclo-oxygenase enzyme."

Stroke 1997 Oct;28(10):2006-11. Acetylsalicylic acid increases tolerance against hypoxic and chemical hypoxia. Riepe MW, Kasischke K, Raupach A.

Cancer Res 1998 Dec 1;58(23):5354-60. Prevention of NNK-induced lung tumorigenesis in A/J mice by acetylsalicylic acid and NS-398. Rioux N, Castonguay A

J Endocrinol 1989 Jun;121(3):513-9. Indomethacin inhibits the effects of oestrogen in the anterior pituitary gland of the rat. Rosental DG, Machiavelli GA, Chernavsky AC, Speziale NS, Burdman JA.

Int J Cancer 2001 Aug 15;93(4):497-506. Cyclooxygenase inhibitors retard murine mammary tumor progression by reducing tumor cell migration, invasiveness and angiogenesis. Rozic JG, Chakraborty C, Lala PK.

Res Commun Mol Pathol Pharmacol 1998 Sep;101(3):259-68. Protective ability of acetylsalicylic acid (aspirin) to scavenge radiation induced free radicals in J774A.1 macrophage cells. Saini T, Bagchi M, Bagchi D, Jaeger S, Hosoyama S, Stohs SJ.

Mol Cell Biochem 1999 Sep;199(1-2):93-102. Antioxidant properties of aspirin: characterization of the ability of aspirin to inhibit silica-induced lipid peroxidation, DNA damage, NF-kappaB activation, and TNF-alpha production. Shi X, Ding M, Dong Z, Chen F, Ye J, Wang S, Leonard SS, Castranova V, Vallyathan V

J Physiol Paris 2001 Jan-Dec;95(1-6):51-7. Protection by aspirin of indomethacin-induced small intestinal damage in rats: mediation by salicylic acid. Takeuchi K, Hase S, Mizoguchi H, Komoike Y, Tanaka A. "Most of non-steroidal anti-inflammatory drugs (NSAIDs) except aspirin (ASA) produce intestinal damage in rats." "ASA did not provoke any damage, despite inhibiting (prostaglandin) PG production, and prevented the occurrence of intestinal lesions induced by indomethacin, in a dose-related manner."

FASEB J 2001 Oct;15(12):2057-72. Cyclooxygenase-independent actions of cyclooxygenase inhibitors. Tegeder I, Pfeilschifter J, Geisslinger G.

J Indian Med Assoc 1997 Feb;95(2):43-4, 47. Role of low dose aspirin in prevention of pregnancy induced hypertension. Tewari S, Kaushish R, Sharma S, Gulati N

J Chromatogr B Biomed Appl 1995 Jul 21;669(2):404-7. Aspirin inhibits collagen-induced platelet serotonin release, as measured by microbore high-performance liquid chromatography with electrochemical detection. Tsai TH, Tsai WJ, Chen CF.

Clin Exp Immunol 1991 Nov;86(2):315-21. Piroxicam, indomethacin and aspirin action on a murine fibrosarcoma. Effects on tumour-associated and peritoneal macrophages. Valdez JC, Perdigon G. "We also studied the effect on tumour development of three inhibitors of prostaglandin synthesis: indomethacin, piroxicam and aspirin. Intraperitoneal administration of these drugs during 8 d was followed by the regression of palpable tumours. Indomethacin (90 mg/d) induced 45% regression, while with piroxicam (two 400 mg/d doses and six 200 mg/d doses) and aspirin (1 mg/d) 32% and 30% regressions, respectively, were observed. The growth rate of nonregressing tumours, which had reached different volumes by the end of the treatment, was delayed to a similar extent by the three anti-inflammatory non-steroidal drugs (NSAID)."

Int J Radiat Biol 1995 May;67(5):587-96. Amelioration of radiation nephropathy by acetylsalicylic acid. Verheij M, Stewart FA, Oussoren Y, Weening JJ, Dewit L.

Semin Perinatol 1986 Oct;10(4):334-55. The role of arachidonic acid metabolites in preeclampsia. Walsh SW, Parisi VM.

Proc Natl Acad Sci U S A 1999 Apr 27;96(9):5292-7. Suppression of inducible cyclooxygenase 2 gene transcription by aspirin and sodium salicylate. Xu XM, Sansores-Garcia L, Chen XM, Matijevic-Aleksic N, Du M, Wu KK. "Aspirin and sodium salicylate at therapeutic concentrations equipotently blocked COX-2 mRNA and protein levels induced by interleukin-1beta and phorbol 12-myristate 13-acetate."

Hum Reprod 1994 Oct;9(10):1954-7. The benefits of low-dose aspirin therapy in women with impaired uterine perfusion during assisted conception. Wada I, Hsu CC, Williams G, Macnamee MC, Brinsden PR. "Higher pregnancy rates (47 versus 17%) were achieved in those taking aspirin from day 1 of HRT." "The addition of low-dose aspirin to a standard HRT protocol in women with impaired uterine perfusion is associated with improved blood flow and satisfactory pregnancy rates."

J Ethnopharmacol 1991 Sep;34(2-3):215-9. Radiation-protective and platelet aggregation inhibitory effects of five traditional Chinese drugs and acetylsalicylic acid following high-dose gamma-irradiation. Wang HF, Li XD, Chen YM, Yuan LB, Foye WO.

Fertil Steril 1997 Nov;68(5):927-30. Low-dose aspirin for oocyte donation recipients with a thin endometrium: prospective, randomized study. Weckstein LN, Jacobson A, Galen D, Hampton K, Hammel J. "Low-dose aspirin therapy improves implantation rates in oocyte donation recipients with a thin endometrium."

Dermatologica 1978;156(2):89-96. Effect of topical salicylic acid on animal epidermopoiesis. Weirich EG, Longauer JK, Kirkwood AH. In contrast to its antihyperplastic effect on pathological proliferation of the epidermis, salicylic acid promotes epidermopoiesis in the normal guinea pig skin. After the application of 1% w/w salicylic acid in acetone-ethanol for 4 weeks, the thickness of the surface epithelium was increased by 40% and that of the deep epithelium by 19%. The mitotic index rose by 17%.

Arch Exp Veterinarmed 1981;35(3):465-70. [Control of implantation in rats and sows by peroral administration of prostaglandin synthetase inhibitors. 2. Effects of prostaglandin F2 alpha, progesterone/estrone, and acetylsalicylic acid on implantation and various biochemical parameters of amniotic fluid in the rat] Wollenhaupt K, Steger H. "The highest number of normally developed (97 per cent) and the lowest number of degenerated foetuses (three per cent) were recorded following acetylsalicylic acid treatment, as compared to the control group (91 and nine per cent)."

Biomed Pharmacother 1999 Aug;53(7):315-8. Aspirin induced apoptosis in gastric cancer cells. Wong BC, Zhu GH, Lam SK

Scand J Immunol 2000 Oct;52(4):393-400. Tamoxifen decreases renal inflammation and alleviates disease severity in autoimmune NZB/W F1 mice. Wu WM, Lin BF, Su YC, Suen JL, Chiang BL. "It has been documented that sex hormone may play a role in the pathogenesis of murine lupus."

Science 2001 Aug 31;293(5535):1673-7. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE.

Since the 1970s, aspirin has been thought of as an inhibitor of prostaglandin synthesis, but that is only part of its effect. Sometimes its effect is the opposite of the effects of other prostaglandin inhibitors.

It protects against the harmful effects of estrogen, prolactin, serotonin, cortisol, histamine, and radiation (u.v., x-rays, gamma rays).

It prevents cancer, and can cause its regression. It inhibits vascular proliferation. It inhibits interleukin 6 (and other inflammatory cytokines), which is a factor in heart disease and breast and liver cancer.

It protects the brain, and can improve learning. It's an antioxidant, prevents cataracts, and protects against glycation in diabetes.

It prevents premature birth and prevents birth defects caused by diabetes, preeclampsia, and exposure to alcohol. It prevents recurrence of neural tube defects and protects against many of the gestational problems associated with lupus.

Although aspirin protects against uncontrolled cell proliferation, as in cancer and psoriasis, salicylic acid increases normal cell division in the skin.

Aspirin protects against many forms of shock and stess, and corrects imbalances in the nervous system.

It protects against several kinds of toxins involved in brain degeneration.

"Aspirin elevated ATP levels not only in intact cortical neurons but also in isolated brain mitochondria, an effect concomitant with an increase in NADH-dependent respiration by brain submitochondrial particles."

De Cristobal, et al., 2002

"The pharmacological action of salicylate cannot be explained by its inhibition of cyclooxygenase (COX) activity." ". . . salicylate exerts its antiinflammatory action in part by suppressing COX-2 induction. . . ." XM Xu, et al., 1999

http://raypeat.com/articles/aging/aspirin-brain-cancer.shtml

查看原帖及回帖 列表