There are small group of enzymes which are specifically suited to the detoxification and removal of 4-HNE from cells. Within this group are the glutathione S-transferases (GSTs) such as hGSTA4-4 and hGST5.8, aldose reductase, and aldehyde dehydrogenase. These enzymes have low Km values for HNE catalysis and together are very efficient at controlling the intracellular concentration, up to a critical threshold amount, at which these enzymes are overwhelmed and cell death is inevitable.

Glutathione S-transferases hGSTA4-4 and hGST5.8 catalyze the conjugation of glutathione peptides to 4-hydroxynonenal through a conjugate addition to the alpha-beta unsaturated carbonyl, forming a more water-soluble molecule, GS-HNE. While there are other GSTs capable of this conjugation reaction (notably in the alpha class), these other isoforms are much less efficient and their production is not induced by the stress events which cause the formation of 4-HNE (such as exposure to hydrogen peroxide, ultraviolet light, heat shock, cancer drugs, etc.), as the production of the more specific two isoforms is. This strongly suggests that hGSTA4-4 and hGST5.8 are specifically adapted by human cells for the purpose of detoxifying 4-HNE to abrogate the downstream effects which such a buildup would cause.

Increased activity of the mitochondrial enzyme aldehyde dehydrogenase 2 (ALDH2) has been shown to have a protective effect against cardiac ischemia in animal models, and the postulated mechanism given by the investigators was 4-hydroxynonenal metabolism.

Recently, research on the effects of HNE on specific proteins as well as on aging has been carried out by Toroser and associates.

Adapted from the Wikipedia article 4-Hydroxynonenal, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

*Mental health services. Individualized treatment designed to assist patients in reaching and maintaining psychiatric stability and in developing the necessary skills and supports to succeed in community settings. Services are provided in the inpatient psychiatric facility and in two community-based apartment buildings.

*Chemical health services. Inpatient and outpatient services, including mental illness/chemical dependency services.

*Sub-acute detoxification services for people in Anoka County who require help or supervision while going through detoxification.

*Community transition services. A multi-disciplinary team of AMRTC staff provide services to discharged patients who have experienced long or frequent regional treatment center hospitalizations and who require help in leaving the facility and/or in remaining in the community.

*Mental Health Initiatives. AMRTC employees work in teams with county staff and private providers to support individuals with severe and persistent mental illness in succeeding in the community.

Adapted from the Wikipedia article Anoka Metro Regional Treatment Center, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

The metabolism of xenobiotics is often divided into three phases: modification, conjugation, and excretion. These reactions act in concert to detoxify xenobiotics and remove them from cells.

Phase I – modification

In phase I, a variety of enzymes acts to introduce reactive and polar groups into their substrates. One of the most common modifications is hydroxylation catalysed by the cytochrome P-450-dependent mixed-function oxidase system. These enzyme complexes act to incorporate an atom of oxygen into nonactivated hydrocarbons, which can result in either the introduction of hydroxyl groups or N-, O- and S-dealkylation of substrates. The reaction mechanism of the P-450 oxidases proceeds through the reduction of cytochrome-bound oxygen and the generation of a highly-reactive oxyferryl species, according to the following scheme:

& & & & mbox{NADPH} + mbox{H}^+ + mbox{RH} rightarrow mbox{NADP}^+ + mbox{H}_2mbox{O} +mbox{ROH} ,

Phase II – conjugation

In subsequent phase II reactions, these activated xenobiotic metabolites are conjugated with charged species such as glutathione (GSH), sulfate, glycine, or glucuronic acid. These reactions are catalysed by a large group of broad-specificity transferases, which in combination can metabolise almost any hydrophobic compound that contains nucleophilic or electrophilic groups. One of the most important of these groups are the glutathione S-transferases (GSTs). The addition of large anionic groups (such as GSH) detoxifies reactive electrophiles and produces more polar metabolites that cannot diffuse across membranes, and may, therefore, be actively transported.

Phase III – further modification and excretion

After phase II reactions, the xenobiotic conjugates may be further metabolised. A common example is the processing of glutathione conjugates to acetylcysteine (mercapturic acid) conjugates. Here, the γ-glutamate and glycine residues in the glutathione molecule are removed by Gamma-glutamyl transpeptidase and dipeptidases. In the final step, the cystine residue in the conjugate is acetylated.

Conjugates and their metabolites can be excreted from cells in phase III of their metabolism, with the anionic groups acting as affinity tags for a variety of membrane transporters of the multidrug resistance protein (MRP) family. These proteins are members of the family of ATP-binding cassette transporters and can catalyse the ATP-dependent transport of a huge variety of hydrophobic anions, and thus act to remove phase II products to the extracellular medium, where they may be further metabolised or excreted.

Adapted from the Wikipedia article Xenobiotic metabolism, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

Essentiale is a preparation of essential phospholipids. Essentiale normalizes the metabolism of lipids and proteins, improves the detoxification function of the liver, restores the cellular structure of the liver and retards the producing of conjunctive tissue. Essentiale medications are indicated for the treatment of fatty degeneration of the liver, hepatitis (including toxic hepatitis, liver damage caused by medicines or alcohol abuse), cirrhosis of the liver, disturbances in liver function associated with different illnesses.

Adapted from the Wikipedia article Essentiale, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

That the exact compounds an organism is exposed to will be largely unpredictable, and may differ widely over time, is a major characteristic of xenobiotic toxic stress. The major challenge faced by xenobiotic detoxification systems is that they must be able to remove the almost-limitless number of xenobiotic compounds from the complex mixture of chemicals involved in normal metabolism. The solution that has evolved to address this problem is an elegant combination of physical barriers and low-specificity enzymatic systems.

All organisms use cell membranes as hydrophobic permeability barriers to control access to their internal environment. Polar compounds cannot diffuse across these cell membranes, and the uptake of useful molecules is mediated through transport proteins that specifically select substrates from the extracellular mixture. This selective uptake means that most hydrophilic molecules cannot enter cells, since they are not recognised by any specific transporters. In contrast, the diffusion of hydrophobic compounds across these barriers cannot be controlled, and organisms, therefore, cannot exclude lipid-soluble xenobiotics using membrane barriers.

However, the existence of a permeability barrier means that organisms were able to evolve detoxification systems that exploit the hydrophobicity common to membrane-permeable xenobiotics. These systems therefore solve the specificity problem by possessing such broad substrate specificities that they metabolise almost any non-polar compound. Useful metabolites are excluded since they are polar, and in general contain one or more charged groups.

The detoxification of the reactive by-products of normal metabolism cannot be achieved by the systems outlined above, because these species are derived from normal cellular constituents and usually share their polar characteristics. However, since these compounds are few in number, specific enzymes can recognize and remove them. Examples of these specific detoxification systems are the glyoxalase system, which removes the reactive aldehyde methylglyoxal, and the various antioxidant systems that eliminate reactive oxygen species.

Adapted from the Wikipedia article Xenobiotic metabolism, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

Introduction

A brief introduction (by Goldacre) touching on subjects covered by subsequent chapters. It bemoans the widespread lack of understanding of evidence-based science.

Chapter 1: Matter

Detoxification methods (the Aqua Detox, ear candles etc.) that can easily be shown to be bogus by simple experiments. Discusses the “detox phenomenon.” Touches on purification rituals.

Chapter 2: Brain Gym

The absurdity of claims for Brain Gym, a programme of specific physical exercises that its commercial promoters claim can create new pathways in the brain. The uncritical adoption of this programme by sections of the British school system is derided.

Chapter 3: The Progenium XY Complex

On cosmetics, and the misleading and pseudoscientific claims by their manufacturers.

Chapter 4: Homeopathy

Homeopathy is used to prompt a discussion of the nature of scientific evidence, with reference to the placebo effect, regression to the mean, and the importance of blind testing and randomisation in the design of fair clinical trials. Having concluded that homeopathic pills have been shown to work no better than placebo pills, the author suggests homeopathy may still have psychological benefits which could be the subject of further study.

Chapter 5: The Placebo Effect

Examples of the amazing power of the mind over pain, anxiety and depression are presented with studies showing how higher prices, fancy packaging, theatrical procedures and a confident attitude in the doctor all contribute to the relief of symptoms. In patients with no specific diagnosed condition, even a fake diagnosis and prognosis with no other treatment helps recovery, but ethical and time constraints usually prevent doctors from giving this reassurance. Exploiting the placebo effect is presented as possibly justifiable if used in conjunction with effective conventional treatments. The author links its use by alternative medicine practitioners with the diversion of patients away from effective treatments and the undermining of public health campaigns on AIDS and malaria.

Chapter 6: The Nonsense ”du Jour”

Nutritionists are accused of misusing science and mystifying diet to bamboozle the public. Misrepresentations of the results of legitimate scientific research to lend bogus authority to nutritionist theories, while ignoring alternative explanations are cited in evidence. The use of weak circumstantial associations between diet and health found in observational studies as if they proved nutritionist claims is criticised. The unjustified over-interpretation of surrogate outcomes in animal (or tissue culture) experiments as proving human health benefits is explored. The cherry picking of published research to support a favoured view is contrasted with the systematic review designed to minimise such bias. The supposed benefits of antioxidants are questioned with studies showing they may be ineffective or even harmful in some cases. The methods used by the food supplement industry to manufacture doubt about any critical scientific reports are likened to those previously used by the tobacco and asbestos industries.

Chapter 7: Dr Gillian McKeith PhD

The Scottish TV diet guru and self-styled “doctor” Gillian McKeith and her scientific claims are dissected. Statements exemplifying her scientific knowledge include that the consumption of dark-leaved vegetables like spinach “will really oxygenate your blood” as they are high in chlorophyll, and that “each sprouting seed is packed with the nutritional energy needed to create a fully-grown, healthy plant”. She is described masquerading as a genuine medical doctor on her TV reality/health shows. Her publications are compared with a Melanesian cargo cult; superficially correct but lacking any scientific substance. Her belief in the special nutritional value of plant enzymes (which are broken down in the gut like any other proteins) is ridiculed. The general problems involved in establishing any firm links between diet and health are examined.

Chapter 8: ‘Pill Solves Complex Social Problem’

Do fish oil capsules make your child smarter? If you lent any credence to British press and TV reports, you might think this link has been firmly established already. The book probes the methodological weaknesses of the widely publicised “Durham trial” where the pills were given to children to improve their school performance and behaviour, but without any control groups and wide open to a range of confounding factors. The failure to publish any results and backtracking on earlier claims by the education authorities is slated. The media’s preference for simple science stories and role in promoting dubious health products is highlighted. Parallels are drawn between the Equazen company behind the Durham fish oil trials and the Efamol company’s promotion of evening primrose oil.

Chapter 9: Professor Patrick Holford

The influence of the best-selling author, media commentator, businessman and founder of the Institute for Optimum Nutrition (which has trained most of the UK’s “nutrition therapists”) is acknowledged. Holford’s success in presenting nutritionism as a scientific discipline in the media, and forging links with some British universities is also noted. The book judges that his success is based on misinterpreting and cherry-picking favourable results from the medical literature, in order to market his vitamin pills. His promotion of vitamin C in preference to AZT as a treatment for AIDS, vitamin E to prevent heart attacks, and vitamin A to treat autism are all condemned as lacking in sound evidential support. His reliance on the work of discredited fellow nutritionist Dr. R.K. Chandra is likewise slated. The Universities of Luton and Teesside are criticised for their past associations with Holford and the ION.

Chapter 10: Is Mainstream Medicine Evil?

The book remarks on the relatively low percentage of conventional medical activity (50 to 80%) which could be called “evidence-based”. The efforts of the medical profession to weed out bad treatments are seen to be hampered by the withholding or distortion of evidence by drug companies. The science and economics of drug development are outlined, with criticism of the lack of independence of industrial research and the neglect of Third World diseases. Some underhand tricks used by drug companies to engineer positive trial results for their products are explored. The publication bias produced by researchers not publishing negative results is illustrated with funnel plots. Examples are made of the SSRI antidepressants and Vioxx drugs. Reform of trials registers to prevent abuses is proposed. The ethics of drug advertising and manipulation of patient advocacy groups are questioned.

Chapter 11: How the Media Promote the Public Misunderstanding of Science

The misrepresentation of science and scientists in the media is attributed to the preponderance of humanities graduates in journalism. The dumbing-down of science to produce easily-assimilated wacky, breakthrough or scare stories is criticised. Wacky “formula stories” like those for “the perfect boiled egg” or “most depressing day of the year” are revealed to be the product of PR companies using biddable academics to add weight to their marketing campaigns. Among other examples, the recent speculation by [http://www.lse.ac.uk/collections/darwin/people.htm Dr. Curry] (a political theorist at the LSE) that the human race will evolve into two separate races, presented as a science story across the British media, is exposed as a PR stunt for a men’s TV channel. The relative scarcity of sensational medical breakthroughs since a golden age of discovery between 1935 and 1975, is seen as motivating the production of dumbed-down stories which trumpet unpublished research and ill-founded speculation. An inability to evaluate the soundness of scientific evidence is seen to give undeserved prominence to marginal figures with fringe views.

Chapter 12: Why Clever People Believe Stupid Things

This chapter is a brief introduction to the research on cognitive biases, which, Goldacre argues, explain some of the appeal of alternative medicine ideas. Biases mentioned include confirmation bias, the availability heuristic, illusory superiority and the clustering illusion (the misperception of random data). It also discusses Solomon Asch’s classic study of social conformity.

Chapter 13: Bad Stats

Covers the cases of Sally Clark and Lucia de Berk where poor understanding and presentation of statistics played an important part in their criminal trials.

Chapter 14: Health Scares

Covers how the press selectively used a “laboratory” that gave positive MRSA results where other pathology labs found none. Creating an “expert” from Chris Malyszewicz who worked from a garden shed.

Chapter 15: The Media’s MMR Hoax

Andrew Wakefield and the MMR vaccine controversy.

And Another Thing=

Further Reading and Acknowledgments

=
Adapted from the Wikipedia article Bad Science (book), under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

The first-born child of Edith and Arthur Gittleman, Gittleman grew up in West Hartford, Connecticut, attending Conard High School (1964–1967) where she graduated with high honors. Active as a Parade of Youth correspondent for the ”Hartford Courant” (coming in 2nd place for the state) and president of the Service Club, she also attended religious school where she taught Hebrew music and dance, although drama was her first love.

As the daughter of a Type-2 diabetic, she suffered early on from low blood sugar (or reactive hypoglycemia) and mild acne. “I was always craving something sweet, a natural way to raise my blood sugar, but the sugar would make my skin react.” Soon she began her own explorations into the science of weight control and beauty that would make her famous later in life.

During her sophomore year at Connecticut College where she was majoring in English (1967–71), Gittleman was “bitten” by the nutrition bug. While many of her contemporaries were experimenting with mind-altering substances, she was experimenting with diets and food.

Her junior year abroad in England at the City of London College became the catalyst for further diet explorations while she was expanding her studies in English literature and exploring both contemporary and Shakespearian theater. During this time, Ann Louise was enamored with the myriad of vegetarian and vegan restaurants in 1970’s London; she also became the client of a well-known naturopathic physician on Baker St. where she was first introduced to the concept of detoxificatio

During the summer of her junior year abroad, Gittleman visited Netanya, Israel, where she studied and lived with the family of a naturopathic physician who was a Natural Hygienist, following a “living foods” raw diet for ten years and a believer in fasting. These topics would be revisited later in many of her books.

Returning back to the States, she graduated from Connecticut College with a bachelor’s degree in English, and after graduation in 1972, she spent a year at the Hayim Greenberg Teacher’s College in Jerusalem, Israel, where she received a certificate in religious education and delivered the commencement address in both English and Spanish.

Back home in West Hartford, Connecticut, she taught religious school, music, and led youth groups for a year after returning from Israel. In February 1974, her life changed forever when she studied with Dr. Hazel Parcells, who had advertised her school for scientific nutrition in Albuquerque, New Mexico in ”Let’s Live” magazine.

“Come to New Mexico for five days that will change your life,” the ad read—and Ann Louise’s life did! The basic premise of Parcells’ teaching—the electromagnetic energy of food and all living things—became the way she directed her own research for many, many years. “Under her tutelage, I learned a great deal including the importance of cleansing the body and foods of parasites, heavy metals, and radiation—a forgotten but critical area of concern.”

“Many of these themes became focal points in my books: the ‘Chemistry in the Kitchen’ section in Beyond Pritikin, the impetus for ”Guess What Came to Dinner? Parasites and Your Health”, and the importance of essential fats for female health concerns in ”Super Nutrition for Women”. Even my ”New York Times” bestselling ”Fat Flush Plan” was partly derived from the understanding of the liver and lymph that I gleaned from Parcells over 30 years ago.”

“When I was in the formative stages of my career, I wanted to focus solely on alternative health because I was so inspired and motivated by the amazing healing results of my work using Dr. Parcells’ methods. Even before I had an accredited nutrition degree, I had established a thriving clientele in my native West Hartford, Connecticut, and I was getting referrals from local health food stores. I became affiliated with various speakers bureaus including the Connecticut Speaker’s Bureau.”

Parcells recognized Ann Louise’s gift for healing and encouraged her to continue her education along more conventional lines. Based on her mentor’s advice, she enrolled at the New York Institute of Dietetics where she was awarded a Dietetic Internship Certificate in 1976. At the Institute, Ann Louise did field work at the Parson’s Hospital in Flushing, New York. During the same year, she obtained a principal and teaching certificate at the Hebrew Union College.

Shortly thereafter, she was accepted in the Master’s degree program for Nutrition Education at Columbia University Teacher’s College. Gittleman was a student of Joan Gussow, MEd, EdD, a pioneer in the movement for local, sustainable food, and Isobel Contento, PhD, Mary Swarz Rose professor of Nutrition and Education, at Columbia University Teacher’s College. She graduated in 1977. [http://www.tc.columbia.edu/news/article.htm?id=3653 www.tc.columbia.edu/news/article.htm?id=3653] She also earned a naturopathic doctor’s degree—in her “spare time”—through correspondence courses at Bernadean University in Van Nuys, California.

In 1993, she became a board certified nutritional specialist through the American College of Nutrition. In 2002, she obtained her PhD in holistic nutrition from Clayton College of Natural Health where she became an adjunct professor and helped develop a certification program for Fat Flush community leaders.

Adapted from the Wikipedia article Ann Louise Gittleman, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

Lofexidine is not an opioid, whereas methadone is. Some opioid detox programs use methadone in decreasing amounts in their detox protocol, whereas other detox programs use lofexidine. The drugs are completely chemically unrelated, and their physiological effects are completely unrelated, although both are used as part of an opioid detoxification protocol. Whereas lofexidine cannot stop opioid withdrawal and merely eases some symptoms of withdrawal, methadone — being an opioid itself — will completely ameliorate all withdrawal symptoms in a sufficient dose. Indeed, one suggested use for lofexidine is to ease withdrawal symptoms of methadone dependence. While abstaining from opiates and taking lofexidine, effective detoxification can succeed in as little as 3 days

, although the standard duration of detoxification using lofexidine is 10 days. The LD50 of lofexidine is 77& mg/kg.

Lofexidine is not currently available in the United States. Britannia Pharmaceuticals has licensed lofexidine to be sold by US World Meds for sale in North America , and clinical trials are currently underway to secure approval for sale in the United States by the U.S. Food and Drug Administration (FDA).

An additional benefit of lofexidine treatment is that it is given as part of an outpatient, or ambulatory regimen, and can be completed without a hospital stay. This reduces costs for both healthcare provider and patient, and keeps specialist hospital beds free for particularly difficult withdrawal cases.

Adapted from the Wikipedia article Lofexidine, under the G. N. U. Free Doc

No related posts.

Some food toxins can be reduced by pressure cooking. A Korean study of aflatoxins in rice (associated with ”Aspergillus” fungus) showed that pressure cooking was capable of reducing aflatoxin concentrations to between 12 and 22% of the amount in the uncooked rice.

Adapted from the Wikipedia article Pressure cooking, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.

The principal physiological function of glyoxalase I is the detoxification of methylglyoxal, a reactive 2-oxoaldehyde that is cytostatic at low concentrations and cytotoxic at millimolar concentrations. Methylglyoxal is a by-product of normal biochemistry that is a carcinogen, a mutagen and can chemically damage several components of the cell, such as proteins and nucleic acids. Methylglyoxal is formed spontaneously from dihydroxyacetone phosphate, enzymatically by triosephosphate isomerase and methylglyoxal synthase, as also in the catabolism of threonine.

To minimize the amount of toxic methylglyoxal and other reactive 2-oxoaldehydes, the glyoxalase system has evolved. The methylglyoxal reacts spontaneously with reduced glutathione (or its equivalent, trypanothione), forming a hemithioacetal. The glyoxalase system converts such compounds into D-lactate and restored the glutathione. In this conversion, the two carbonyl carbons of the 2-oxoaldehyde are oxidized and reduced, respectively, the aldehyde being oxidized to a carboxylic acid and the acetal group being reduced to an alcohol. The glyoxalase system evolved very early in life’s history and is found nearly universally through life-forms.

The glyoaxalase system consists of two enzymes, glyoxalase I and glyoxalase II. The former enzyme, described here, rearranges the hemithioacetal formed naturally by the attack of glutathione on methylglyoxal into the product. Glyoxalase II hydrolyzes the product to re-form the glutathione and produce D-lactate. Thus, glutathione acts unusually as a coenzyme and is required only in cata

The glyoxalase system has also been suggested to play a role in regulating cell growth and in assembling microtubules.

Adapted from the Wikipedia article Lactoylglutathione lyase, under the G. N. U. Free Documentation License. Please also see http://en.wikipedia.org/wiki

No related posts.