Detoxification and Cleansing Programs

Total Wellness Cleanse

The Total Wellness Cleanse is the newest and most rewarding health-promoting program. This 30-day cleanse is the first of its kind. Nothing like this has ever been done before. It is the only highly-supportive cleansing program that will guide members every single day through a 14-day cleansing process that is geared towards removing dietary stressors, enhancing the body's pH balance, and providing holisitic nutrition guidelines for healing the body's compromised organs and systems. The subsequent 2 weeks (the maintenance phase) is dedicated to working one-on-one with each member to ensure that they transition properly into their customized dietary and lifestyle plans. The result customers will experience greater health, energy, and weight loss improvements than they could ever possibly imagine. The cleanse was created by renowned holistic nutritionists and wellness coaches, Yuri Elkaim and Amy Coates of Total Wellness Consulting. Continue reading...

Total Wellness Cleanse Summary


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Metabolic function and detoxification

The liver receives the effluent of the splanchnic circulation and is located directly upstream from the pulmonary circulation and cardiac pump, an arrangement adapted to its involvement in metabolic and detoxification functions. The liver is the main site of protein synthesis, for example albumin, which is a key element in maintaining oncotic pressure, and a site of binding for numerous hormones and drugs. It also synthesizes coagulation factors, which may (e.g. factors II, VII, IX, X) or may not (factors V, XI, XII, XIII, and fibrinogen) be dependent on vitamin K. The liver is essential for carbohydrate metabolism by increasing glycogen synthesis when the serum glucose concentration is high, and by degrading glycogen or converting amino acids to glucose by gluconeogenesis when serum glucose concentration is low. With regard to fat metabolism, the liver is responsible for both chylomicron degradation via acetyl-coenzyme A and lipoprotein synthesis during which fatty acids are...

Fsr a Sulfite Detoxification Tool and an Assimilatory Enzyme

In cells receiving sulfite, Fsr and methylcoenzyme M reductase subunits are expressed at comparable levels (Fig. 16.3b) the latter is a catabolic enzyme and represents up to 30 of the cellular protein in a methanogen (Rouviere and Wolfe 1987 Thomas et al. 1987). From the data presented in Sect. 16.7, it can be calculated that the extracts of Methanocaldococcus jannaschii grown with sulfite reduce this oxyanion with H2F420 at a rate of 2.7-3.7 imol min-1 mg-1 protein. With reduced methylviolo-gen as the electron donor, this rate would be 8.1-18.5 imol min-1 mg-1 protein. With A. fulgidus, where sulfite reductase is an energy-metabolism enzyme, cell extract sulfite reductase activity as measured with methylviologen is 0.07 imol min-1 mg-1 protein (Dahl et al. 1994). This comparison shows that Methanocaldococcus jannaschii Fsr behaves like a catabolic enzyme. Upon centrifugation at 160,000g, about 26 of the cell extract Fsr activity is found in the pellet fraction and 65 in the denser...

Decreased Detoxification of the Reactive or Toxic Metabolite

Bioinactivation of toxic metabolites can be nonenzymatic, for example, conjugation with glutathione. However, in many cases, detoxification may be catalyzed by a number of enzymes. In this respect, the glutathione-S-transferases (GST) have attracted a great deal of interest, in particular in the field of cancer, where deficient detoxification of environmentally derived carcinogens, for example, from smoking, has been implicated in the pathogenesis of cancer (82,83). However, the GST superfamily, many members of which are polymorphically expressed (84), is also important in the detoxification of drugs, and thereby in the pathogenesis of ADRs. There are three examples where GST polymorphisms have been shown to play a possible role

Relevance Of Peroxiredoxincatalyzed Peroxynitrite Detoxification

Peroxynitrite's relevance in biochemistry was first noted by Beckman et al. (1990) and Radi et al. (1991) and during the next ten years evidence of the formation of this oxidant in vivo accumulated. Initially considered a toxic species, peroxynitrite, like H2O2 (Rhee, 2006), has recently started to be regarded as potentially involved in redox signaling pathways (Bachschmid, et al., 2005 Touyz, 2005). By 2000, the mechanisms that control peroxynitrite toxicity and possible signaling functions remained unclear It was known that the reaction with carbon dioxide represented one important pathway of decay, but this reaction represented only a diversion of reactivity from peroxynitrite to carbonate radical (CO3-), which also is an oxidizing species, and therefore cannot be regarded as a true detoxification pathway. Analogous considerations applied for the fast reactions between peroxynitrite and some heme proteins (Table 3), except for the case of oxyhemoglobin that isomerizes peroxynitrite...

Skin And Appendages As Secretory Organ For Metals

While urinary and biliary excretion are the primary routes of elimination of xeno-biotics, for certain agents such as metals and their compounds, the skin with its excretory pathways and appendages also represents an important elimination route. As a general rule, metals with affinity for sulfhydryl groups, and thereby keratin-rich tissues, also find significant excretion via skin, hair, sweat, nails, and ear wax. The skin thus plays a role in detoxification as well as in maintaining an appropriate balance of certain essential elements. Integumentary losses of body minerals occur on a continuing basis and can be useful in the assessment of essential nutrient stores, environmental exposure to toxics, or disease. For instance, copper and iron, eliminated excessively under certain conditions through

Genetic Variation and Pharmacology

One example is the relationship of genetic variation in the enzyme thiopurine methyltransferase with the efficacy and toxicity of the thiopurine drugs (Weinshilboum, 2001). Individuals with reduced-activity variants of this enzyme are at elevated risk of drug-induced toxicity from standard treatment regimens. These same dosages have reduced impact on disease or efficacy in other individuals with hyperactive variants of this enzyme, as the drug is rapidly inactivated in these individuals. Other well-characterized examples of clinically relevant variation include the genes in the CYP3A family and CYP2D6, genes encoding proteins with roles in the activation and detoxification or inactivation of many drugs. Several recent reviews and commentaries include discussions of the current state of application of pharmacogenetics in the clinical laboratory and medical practice (Wolf et al., 2000 Kalow, 2001a 2001b McLeod and Evans, 2001 Shi et al., 2001 Zanger et al., 2001...

Transcriptional Regulation of Cellular Antioxidant Defense Mechanisms

Reactive oxygen species (ROS) are constantly generated in human body. Enzymatic and nonenzymatic antioxidants detoxify ROS and minimize damage to biomolecules. An imbalance between the production of ROS and cellular antioxidant capacity leads to a state of oxidative stress'' that contributes to the pathogenesis of a vast variety of clinical abnormalities (1-3). The susceptibility of the target organs or cells to oxidative injury depends largely on their capability to control protective ROS scavenging systems. The primary endogenous antioxidants are present normally at low levels in human tissues and are not timely induced when exposed to oxidative

Molecular Targets For Chemopreventive Action Of Dietary Components

This outline of genetic changes can be used as a structure for illustrating the chemopreventive actions of dietary components in cancer prevention. Ample evidence exists to demonstrate that bioactive compounds can act in each of these areas. Table 2.2 cites several examples of molecular targets and representative nutritional factors that can act at these sites.2728 The overview presented in this chapter is by no means a comprehensive catalog of all bioactive compounds, nor of all of their defined mechanisms of actions. Note that most compounds have a pleiotropic action that is, they can act at a number of sites in the carcinogenesis pathway. In addition, many different compounds can act on a single molecular target. We outline one example of a nutrient, the active form of vitamin D, 1a,25-dihydroxyvitamin D3 , with many different mechanisms of cancer preventive action. The activities of many other compounds are further detailed in later chapters. Note that all of the biochemical and...

Lynne T Haber PhD Joan S Dollarhide Ms Mtsc Jd Andrew Maier Ms Cih Michael L Dourson PhD DABT

Two paracetamol Tylenol tablets will relieve the minor aches and pains Twenty-two tablets are fatal So why is not all paracetamol a danger The answer to the paracetamol puzzle is that there are two pathways down which our bodies dispose of this drug. Most is removed by converting it to a sulphate and this works fine provided there is no sudden excess that uses up our supply of sulphate enzymes. If this happens the body has another way of removing paracetamol, by oxidizing it. Unfortunately, this produces a toxic chemical that requires glutathione to detoxify it. It is only when the supply of glutathione is exhausted that the toxin is fatal (1).

Biochemical and Evolutionary Aspects of Eukaryotes That Inhabit Sulfidic Environments

Abstract Various eukaryotes inhabit environments that harbor high concentrations of sulfide, which is a potent inhibitor of complex IV in the mitochondrial respiratory chain. They must therefore posses means by which they can detoxify sulfide, or use alternative electron routes that circumvent oxygen as the terminal acceptor, or both. The biochemical mechanisms through which eukaryotes deal with sulfide are beginning to come into focus, with sulfide quinone oxidoreductase and the energy metabolism germane to anaerobic mitochondria standing in the foreground. This chapter briefly covers current progress in understanding the biochemistry of sulfide detoxification and utilization by eukaryotes. In light of newer views of ocean geochemistry ( Canfield oceans), both the anaerobic biochemistry of mitochondria and their capacity to deal with sulfide are most easily interpreted as evolutionary holdovers from the anoxic and sulfidic phase of ocean history between about 2.3 billion and about...

Nrf2Mediated Antioxidant Defense

ARE is a cis-acting regulatory element or enhancer sequence, which is found in promoter regions of genes coding phase II detoxification enzymes and antioxidant proteins. Okuda et al. (60) described an enhancer element which is similar to element or AP-1 site in the rat glutathione S-transferase-P gene. Subsequently, it was also found in the promoter regions of mouse glutathione S-transferase Ya (61), and human NAD(P) H qui-none oxidoreductase 1 (62) genes.

The Role Of Viruses In Type B Adverse Drug Reactions

Evidence for the role of viruses first came from the observation that the use of ampicillin in patients with active EBV infection (i.e. infectious mononucleosis) results in a rash in 95 of patients (Sullivan and Shear, 2001). Another member of the herpes virus family, human herpes virus 6 (HHV6) has recently been implicated in hypersen-sitivity reactions associated with a number of drugs, including sulphasalazine (Suzuki et al., 1998 Descamps et al., 2001). However, whether this is a true predisposition or merely a coincidental factor needs further study. Perhaps the most striking association between viral infection and drug hypersensitivity has been observed in HIV-infected individuals. These patients have a higher frequency of hypersensitivity reactions with numerous anti-infective drugs including co-trimoxazole, sulphadiazine, dapsone, clindamycin, primaquine, and thioacetazone (Koopmans et al., 1995 Pirmohamed and Park, 2001b). This has been best shown with co-trimoxazole that is...

C T De Rosa PhD H Hansen S Wilbur H R Pohl H A ElMasri M M Mumtaz

We live in a chemical world, and exposure to xenobiotics is a fact of life. Humans are exposed daily to a variety of chemicals including but not limited to large categories of pesticides, pharmaceuticals, household products, and food additives. Chemical exposures can be intentional or unintentional, to a single chemical or to a mixture of chemicals. Exposures to environmental chemicals occur in populations living in inner cities near chemical manufacturing plants (1, 2) hazardous waste sites, and in the near field runoffs from fields and fertilizers (3). An overturned cargo train or transportation truck can spill chemicals in a pristine environment and become a source of pollution, contamination, and exposure, and eventually lead to an emergency response event. Exposures to environmental chemicals can affect humans, animals, and plants. Thus people of various interests and backgrounds are concerned about environmental exposures. Everyone carries a body burden of chemicals that range...

The Possible Functions of SQRRelated Genes in Eukaryotes

Such findings suggest that even such animals that are not exposed to environmental sulfide nonetheless require biochemical means of dealing with sulfide, albeit at lower concentrations than those experienced by sulfide-exposed marine invertebrates. Failure to deal with endogenous sulfide can have dire consequences in humans. For example, overproduction of sulfide owing to enhanced CBS activity can exacerbate cognitive effects in Down-syndrome patients (Chadefaux et al. 1985 Kamoun 2001) and insufficient detoxification of sulfide produced in the human colon can lead to inflammatory diseases and might affect the frequency of colon cancer (Pitcher et al. 2000). Whether mammalian SQR plays a significant physiological role in sulfide metabolism, or not, remains to be shown.

The Glutathionestransferases

Individuals with polymorphisms in the GST Phase II detoxification genes have a decreased rate of detoxification, with a corresponding increase in levels of carcinogen DNA adduct formation and also an increased level of chromosomal aberrations (36,37). Cruciferous vegetables, such as broccoli, and members of the allium family, such as garlic and onion, have been shown to be potent inducers of these enzymes, which would be expected to increase clearance of potential toxins from the body (38,39).

The Effect Of Various Detergents

Studies were done also with some commonly used detergents (e.g., sodium lauryl sulphate, cetylammonium bromide, polyoxyethylene stearate, Tween 20, benzalkonium chloride). Two rapid methods were developed for the determination of their activity. One approach was to inject a mixture of a lethal dose of endotoxin and a tolerated concentration of the detergent intraperitoneally into animals. If the detergent applied could detoxify endotoxin, the mortality of the animals was decreased. According to the second procedure the animals were sensitised to endotoxin by lead acetate. In this case microgram quantities of endotoxin could be used, mixed with detergent and given intravenously. Here it was also necessary to titrate detergent toxicity prior to its use. Again, a decrease in mortality indicated the anti-endotoxic effect of the detergent investigated. These experiments indicated that sodium deoxycholate and bile obtained from vari-

Other Non DsrAB Dissimilatory Sulfite Reductases

A new type of SR, Fsr, was recently discovered in the methanogenic archaeon Methanocaldococcus jannaschii (Johnson and Mukhopadhyay 2005). Although sulfite can be inhibitory to methanogens (Balderston and Payne 1976), other methanogens such as M. jannaschii, a strictly hydrogenotrophic, thermophilic microorganism, not only tolerate but even grow with sulfite as the sole source of sulfur (Daniels et al. 1986 Rothe and Thomm 2000). Fsr is an unusual, chimeric protein, with the N-terminal half being an H2F420 dehydroge-nase and the C-terminal half being a siroheme SR, which might have been generated by fusion of a laterally acquired DSR gene and a fqoF or fpoF gene, coding for an H2F420 dehydrogenase subunit (Johnson and Mukhopadhyay 2005). The physiological role of Fsr appears to be detoxification of sulfite rather than sulfite-reduction-based energy production, as M. jannaschii could thus far not been grown with acetate (as the sole carbon source), hydrogen, and sulfite. In the...

Bile Deficiency And Radiationinduced Intestinalsyndrome

It is clear that the intestinal syndrome associated with radiation disease is caused by bacterial endotoxins. Because bile acids are capable of endotoxin detoxification and bile deficiency permits the absorption of endotoxins into the bloodstream ('translocation'), one may ask the question whether or not bile deficiency would play a role in radiation disease. For this reason we studied in rats the effect of experimental bile deficiency on the development of radiation-induced intestinal syndrome. It was observed that the rats having bile fistulas died of radiation disease within five days, whereas the control irradiated and sham-operated irradiated animals survived for 11 days. Apparently bile deficiency accelerated the development of endotoxaemia in this model 44J.

Chapter References

Hayashida, M., Alterman, A.I., McLellan, T., et al. (1989). Comparative effectiveness and costs of inpatient and outpatient detoxification with mild-moderate alcohol withdrawal syndrome. New England Journal of Medicine, 320, 358-65. 5. Bennie, C. (1998). A comparison of home detoxification and minimal intervention strategies for problem drinkers. Alcohol and Alcoholism, 33, 157-63. 47. Paille, F.M., Guelfi, J.D., Perkins, A.C., Royer, R.J., Steru, L., and Perot, P. (1995). Randomised multicentre trial of acamprosate in a maintenance programme of abstinence after alcohol detoxification. Alcohol and Alcoholism, 30, 239-47. 48. Pelc, I., Verbanck, P., Le Bon, M., Gavrilovic, M., Lion, K., and Lehert, P. (1997). Efficacy and safety of acamprosate in the treatment of detoxified alcohol-dependent patients a 90-day dose finding study. British Journal of Psychiatry, 171, 73-7.

Location and intensity of treatment Specialist treatments

Studies comparing inpatient versus outpatient alcohol detoxification have generally found the two approaches to be equally effective. For example, Hayashida et al.'(1,2) randomized 164 male military veterans to inpatient and outpatient detoxification. At 6 months's follow-up no differences in outcome were found between the two groups. Indeed, outpatient detoxification is generally regarded as the treatment of choice for the majority of patients. ( , It should be noted, however, that studies comparing inpatient and outpatient treatment (including detoxification) have tended to exclude patients with particularly poor prognosis (e.g. poor social circumstances, severe psychiatric or physical comorbidity, those at risk of harm to themselves or others). Hence, the clinician needs to interpret the research evidence with caution in the usual clinical setting. However, it is probably safe to assume that in 'uncomplicated' alcohol dependence there is no evidence of an advantage of inpatient...

Exclusion and Sequestration

Many plants detoxify heavy metals by sequestering them in the vacuoles 4 . This plant-specific metal detoxification strategy (animal and bacterial cells do not possess this organelle) provides an efficient form of protection because the vacuole does not contain any sensitive enzymes. When vacuolar sequestration is the major detoxification mechanism, nickel tolerance is often associated with elevated nickel accumulation an extreme form of this sequestration is found in hyperaccu-mulator plants (see Section 4). In most heavy-metal-tolerant plants, the vacuolar sequestration occurs mainly in nonphotosynthetic cells of the epidermis, reducing toxicity to the heavy metal sensitive photosynthetic apparatus 95,136-139 .

Resistance Mechanisms

Resistance mutations either modify the sensitive site or the membrane transport systems involved in influx and efflux of the fungicidal molecule, or they affect the ability for toxification or detoxification. Examples illustrating the operation of these mechanisms follow.

What is meant by the harmreduction approach

In the early 1980s, a radical departure from the conventional abstinence-oriented approach took place when it was appreciated that 'the spread of HIV is a greater danger to individual and public health than drug misuse'. (23 A harm-reduction philosophy is centred on the belief that it is possible to exert a powerful impact upon morbidity and mortality without necessarily insisting upon abstinence. A hierarchy of aims begins with attempts to make contact with as many problem drug users as possible in order to provide access to clean needles and syringes, advice about safer sex and injecting, basic health care, and help with housing, child care, or legal issues. Then, for some people but not all, a move away from street drugs on to a prescribed oral substitute may be feasible, possibly followed by detoxification and rehabilitation.

Assessment of the opiate user

Past treatments and abstinent periods Have they ever been in contact with treatment services or been maintained on substitute medication Have they ever been an in- or outpatient at a detoxification unit What was their longest period of abstinence What has helped in the past When and why did relapses occur What are high-risk situations and other triggers for use

The range of service providers and the impact of treatment

Those who experience problems with opiates may present to wide range of professionals within the health-care, social, and legal systems. The range of treatment options available within statutory and non-statutory agencies will vary, as will the provision of either maintenance or detoxification for opiate dependents depending upon differing treatment philosophies and treatment settings. Partly in response to this diversity of resource provision, an ongoing multicentre prospective outcome study (National Treatment Outcome Research Study) was set up in 1995 to compare the impact of different treatment approaches on subsequent drug use as well as upon psychosocial and physical outcomes. Preliminary results2** suggested that all four types of intervention (residential rehabilitation, inpatient drug dependency units, methadone maintenance, and reduction) led to reductions in illicit drug use and criminal activity as well as reductions in injecting and sharing behaviours. Least impact was...

Clinical Development

A genetic basis for drug response is not a new concept. As early as 1902, Archibald Garrod hypothesized that genetic variance in a biochemical pathway for the detoxification of a foreign substance was the cause of alcap-tonuria (Garrod, 1902). During World War II, it was noted that hemolysis related to antimalarial treatment was much more common among African American soldiers, leading to the identification of inherited variants of glucose-6-phosphate dehydrogenase (G-6-PD). It was during this time that scientists discovered that the prolonged muscle relaxation and apnea after suxamethonium in some patients was due to an inherited deficiency of a plasma cholinesterase. Peripheral neuropathy was observed in a significant number of patients treated with the antituberculosis drug isoniazid, leading to the identification of genetic differences in acetylation pathways.

The Perfused Rat Liver An Intact Organ ModeL of the Liver

The perfused rat liver is an intact organ model that, compared to cultured hepatocytes, preserves tissue structure, 3D hepatocyte anchoring to the ECM, polarity of the parenchymal cells, liver cell heterogeneity, acinar construction, and gene expression gradients along the acinus (Sies, 1978). The perfused rat liver is a well-established experimental system used to study hepatic signal transduction, gene expression, metabolism, hepatobiliary transport, and detoxification. A detailed description of the experimental setup is presented elsewhere (vom Dahl and Haussinger, 1997). This section briefly outlines methods used for the investigation of integrin-dependent osmosensing in rat liver.

The user in withdrawal

If the regular supply of a psychoactive drug (especially sedative drugs such as opiates, barbiturates, benzodiazepines, and alcohol) is interrupted to the dependent user, a classic withdrawal syndrome is likely to develop (e.g. opiate withdrawal syndrome). The nature of the withdrawal syndrome will be determined by the substance group (e.g. opiates, cocaine, benzodiazepines, etc.) whilst the time course of the syndrome will be determined more by the specific drug used (e.g. methadone, heroin). The user in withdrawal from opiates, hypnotics sedatives, and in some circumstances cocaine may require special short-term detoxification. Detoxification describes a process of supportive medical care and usually pharmacotherapy for neuroadaptation reversal to facilitate a return to abstinence and physiologically normal levels of functioning. (41 Medically supervised detoxification can be delivered in inpatient, residential, or outpatient settings. Detoxification should not be considered in...

The recovering dependent drug user

Dependent drug users who attain abstinence may require continuing specialist treatment delivered in a residential setting. Maintaining the commitment to altering a drug-oriented lifestyle is a major and enduring task for many individuals and there are relatively few contemporary services to support this. The treatment philosophy and operation of residential rehabilitation programmes varies quite widely. In the United States, the majority are therapeutic communities and are based on the 12-step or Minnesota Model. The programme length of therapeutic communities varies from short term (e.g. 6 weeks) with aftercare to long-term programmes with a duration of over 1 year. Common to all therapeutic communities is an emphasis on peers and staff as role models for recovery. For some individuals, detoxification can be a gateway into drug-free counselling. Achieving a drug-free state is necessary for entry into many residential rehabilitation programmes or (for opiate users) to receive relapse...

Coordination at local and government levels

In many communities a continuum of care should be made available, including direct provision or access to harm-minimization services (needle syringe exchange, vaccination programmes and safer injecting, and drug use advice), community substitution treatment (methadone or other appropriate opiate agonist prescribing services for stabilization, maintenance, and detoxification), and inpatient and residential programmes (detoxification, therapeutic communities and other rehabilitation programmes, and after-care support). Services providing advice, information, assessment, and referral are an important resource and valuable point of contact for individuals, friends, and families. Structured provision of counselling and support are often made available by these services. Additional gateway services (e.g. outreach services seeking to identify problem users not in touch with treatment services and encouraging referral) are also useful elements of an integrated system.

General Comments

An essential trace metal in its trivalent form, chromium in low concentrations is environmentally ubiquitous and vital for several important biological processes. At high concentrations, on the other hand, particularly in the hexavalent state, chromium is toxic, genotoxic, and carcinogenic in animals and humans. Many barriers exist, however, that limit the uptake and distribution of the element in its more toxic hexavalent form. The most effective detoxification process is its reduction to poorly absorbed Cr3+ in the reducing environments found in body tissues and fluids such as saliva, gastric juice, gastrointestinal bacteria, blood plasma, or the liver (1). Direct inhalation of hexavalent chromium compounds resulting from certain industrial activities appears to comport the highest risk of tumor formation (2). As observed with lead, chromium can exchange between plasma and contacting bone surfaces to be ultimately incorporated into actively mineralizing bone (3). Normally, intake of...

Frataxin function and pathogenesis

It has been proposed that frataxin stimulates ISC synthesis because it is an iron cha-perone. In the mitochondrial environment, frataxin would deliver iron to biosynthetic enzyme complexes and protects it from free radical attack. When mitochondrial iron is high, frataxin would also be able to detoxify and store the metal in a redox inactive form (O'Neill, 2005).

Thiosulfate Sulfur Transferases from Aferrooxidans

Recently, new rhodanese-like proteins were identified, the expression of which is regulated depending on the growth substrate and is probably related to sulfur metabolism and or oxidation (Acosta et al. 2005). Eight nucleotide sequences containing a single rhodanese domain are present in the genome of A. ferrooxidans ATCC 23270 (Fig. 7.1) p11, p14, p14.3, p15, p16, p16.2, p21, and p28 (Acosta et al. 2005). Amino acid sequence comparisons of all eight proteins allowed us to identify the potential catalytic cysteine residues and other highly conserved rhoda-nese family features. The genomic contexts of some of the rhodanese-like genes suggested their implication in sulfur oxidation and metabolism, formation of FeS clusters and detoxification mechanisms. Several of the putative rhodanese genes were successfully isolated, cloned, and overexpressed in Escherichia coli and their TST and 3-mercaptopyruvate cyanide sulfur transferase (MST) activities were determined. On the basis of their...

Generation of Safer Foods for Patients

We have also tested the possibility to detoxify gluten by introducing amino acid substitutions at positions critical for HLA-DQ2 binding or T cell recognition. First, we analyzed natural variants of a LMW-glutenin peptide. While some of these variants possess T cell stimulatory properties, others do not. As the only difference between these peptides was a proline to leucine substitution at position 8 of the peptide this indicated that this substitution was sufficient to abrogate the T cell stimulatory properties of the glutenin peptide (Vader et al., 2003a). Similarly, a proline to glutamine substitution in an alpha-gliadin peptide had a severe impact on the T cell stimulatory properties (Vader et al., 2003a). A subsequent analysis of codon usage in gluten revealed that single base-pair substitutions in gluten genes would suffice to introduce the proline to leucine and proline to glutamine substitutions in gluten proteins (Vader et al., 2003a). These results indicate that genetic...

Inherited Susceptibility Factors

The second group of inherited susceptibility factors for meningioma consists of genes that exhibit low penetrance but appear in human populations with a high frequency. Glutathione S-transferase and cytochrome P450 are examples of genetic polymorphisms that affect the ability of the body to detoxify carcinogens, including those that can induce meningiomas in laboratory animals. Both GST-T1 null and P450 CYP2D6 poor metabolizer alleles are associated with a significantly elevated risk for menin-gioma development. Clearly, GST and P450 genes, as well as other polymorphic genes that are involved in the metabolism of carcinogenic compounds found in diet, cigarette smoke and some industrial chemicals, may be promising candidates to explain the gene-environment interactions in meningioma development.

Metabolic pathways link all three aspects of the ecogenetic theory

One link between all three main components of the ecogenetic theory for PD involves the body's ability to deal with endogenous or exogenous molecules that may be directly or indirectly neurotoxic this ability is manifest in metabolic or detoxification pathways. Such pathways are responsible for the removal of environmental exposures including certain pesticides and components of cigarette smoke. They are made up of enzymes such as the CYP enzymes, the activity of which are subject to the influences of commonly occurring genetic polymorphism. Furthermore, the influence of normal ageing can result in

Triggers of Axonal Injury in Patients with MS

Ronal destruction can be ameliorated in vivo through the blockade of AMPA-type glutamate receptors. Pathological studies in MS lesions indicate that there may be a disturbance of glutamate homeostasis within actively demyelinat-ing plaques. These data suggest an increased synthesis of glutamate within the lesions, which may occur in parallel with a decreased detoxification of glutamate by astrocytes (Werner et al., 2001). Although in experimental studies an axonoprotective effect of AMPA receptor blockers has been described (Pitt et al., 2000), direct evidence for the expression of the respective glutamate receptors on demyelinated axons is lacking. It is not clear, therefore, whether axonal damage is mediated through a glutamate effect on the axon itself or through damage of neuronal cell bodies leading to secondary axonal degeneration.

Deficient Enzyme Activity Leading to Rerouting of Metabolism

If a metabolic pathway that is responsible for the detoxification of a drug is deficient in an individual, the drug may be rerouted via another pathway that may lead to the formation of a toxic metabolite. This has been suggested for phenacetin, an analgesic that was withdrawn from the United Kingdom because of its potential to cause nephrotoxicity, carcinogenicity, and methaemoglobinemia (57-59). The first step in phenacetin metabolism is O-de-ethylation by cytochrome P450 1A2 (CYP1A2), which results in the formation of paracetamol. Further metabolism involves conjugation with glucuronide, sulfate, or glutathione that enables urinary excretion of the products. CYP1A2 metabolism has been implicated in toxicity of phenacetin (60,61). Numerous polymorphisms have been shown in the CYP1A2 gene, some of which are capable of altering the metabolic capacity of the enzyme (62-64). Low catalytic activity of CYP1A2*11 allelic variant leads to reduced phenacetin O-de-ethylation (64). Peters et...

S Miksys and R F Tyndale

Disease have been identified, as have some toxins that can cause a Parkinson's diseaselike syndrome, such as catecholamines, amphetamine, pesticides, tetrahydroisoquinoline (TIQ) and (MPTP). Since 1985, efforts have been made to elucidate the role of drug-metabolizing CYPs in the development of Parkinson's disease, as these enzymes, in particular CYP2D6, are able to inactivate or activate many of these neurotoxins. CYP-mediated reactions can also create neurotoxic free oxygen radicals, and the balance of the neuroprotective and neurotoxic roles of specific brain CYPs requires elucidation for Parkinson's disease and other CNS disorders. Parkinson's-inducing toxins, or their neurotoxic metabolites, can be taken up into dopaminergic neurons by the dopamine transporter, where they cause oxidative stress, mitochondrial dysfunction, and eventually cell death. CYPs are expressed in neurons in human brain (Miksys and Tyndale, 2002, 2004), including dopaminergic neurons of substantia nigra and...

Use of Toxicological Data in Evaluating Chemical Safety Gloria Rachamin PhD

Metabolism is a term that refers to the total fate of a chemical in the body, including its absorption into systemic circulation, distribution to organs and tissues, biotransformation, and excretion. Absorption of a chemical into the blood and distribution in the body depend on the physicochemical characteristics of the substance. Depending on the specific chemical, biotransformation of the chemical usually occurs primarily in the liver and can result in chemical detoxification or activation to a toxic metabolite. Toxic chemicals and their metabolites are excreted via the kidneys or the lungs. Toxicokinetics

Mutagenic Chemicals Can Be Detected by Reversion

Certain chemicals (pro-mutagens) are only mutagenic after metabolic conversion to active derivatives. In animals this is usually due to liver enzymes such as cytochrome P450 that are intended to detoxify harmful chemicals by oxidation. When testing for pro-mutagens, an extract containing such rat liver enzymes is mixed with the bacteria in the Ames test. Recently, genes for some variants of human cytochrome P450 have been cloned and successfully expressed in the Salmonella strains used for mutagen testing. The resulting bacteria synthesize the liver enzymes internally and are much more sensitive in their response to pro-mutagens.

Cholesterol And Toxins

When patients who presented with high cholesterol levels (over 240 mg ) had their mercury amalgams and sources of dental infection removed, these levels usually dropped dramatically within a few days. Generally, the only exceptions occurred in patients who initiated an unforeseen rapid rate of detoxification after the dental revision. A rapid rate of detoxification can keep blood toxin levels elevated. This in turn will usually stimulate the continued elevation of blood cholesterol levels. When such a brisk detoxification is present, cholesterol levels remained elevated for a longer period of time, apparently helping to protect the body from the toxins being released from internal tissue storage sites. Even in the case of these patients, however, cholesterol levels would nearly always decline dramatically at a later date, as the patient continued to detoxify and the detoxification rate and total body toxin load gradually lessened. As long as the toxin levels in the blood declined, the...

Treatment for Alcoholism

The immediate concern in the treatment of alcoholics is detoxification and management of the ethanol withdrawal syndrome. Once the patient is detoxified, long-term treatment requires complete abstinence, psychiatric treatment, family involvement, and frequently support from lay organizations such as Alcoholics Anonymous.

Invivo Redox Effects of Antioxidants

One antioxidant that has received quite a bit of attention is beta-carotene. In a large trial on smokers (the Beta-Carotene and Retinol Efficiency Trial), researchers found that 30 milligrams of beta-carotene per day actually increased lung cancer rates.149-154 Reasons for this unexpected effect are still uncertain but are probably due to oxidation of beta-carotene in the free-radical-rich environment of a smoker's lungs and or the altered metabolism of beta carotene caused by changed detoxification enzymes in the smoker's lungs.155 One other factor may have been the high plasma concentration of beta-carotene produced, relative to that provided by normal dietary intake. For example, one in-vitro study reported that at concentrations created by normal dietary intake (1 to 3 pM), beta-carotene provided protection from oxidative DNA damage. However, at concentrations just above this level (4 to 10 pM, as can be produced during supplementation), the protection was lost and beta-carotene...

Group 2 Classic Sulfite Oxidizing Enzymes and Nitrate Reductases

So far all characterized members of this enzyme family are true SDHs with a periplasmic location and a haem c binding second subunit. One example of such a protein is the recently characterized Campylobacter jejuni SDH (Myers and Kelly 2005) that cross-reacts with anti-Starkeya novella SDH antibodies. The Campylobacter SDH has been suggested to be involved in survival of Campylobacter under microaero-bic conditions in the environment or to serve as a mechanism for detoxification of sulfite (Myers and Kelly 2005).

Bioaerosols and Disease Donald E Gardner PhD

A wide variety of gaseous and particulate airborne pollutants that may be present in the workplace can adversely affect the normal functioning of the host's defenses. Although the lung has an array of effective defense mechanisms available to kill, detoxify, and remove inhaled substances, numerous inhaled metals (e.g., Ni, Cd, Pb, V, and Mn), gaseous pollutants (e.g., NO2, O3, SO2, phosgene,

Genomic Pathogenicity Islands in the Lpneumophila Genomes

Another example of the particular structure of these islands in L. pneumophila is a region containing a 40-kbp genomic island encoding several efflux pumps induced in contact with the host cell and apparently dedicated to detoxification and proper metal ion balance within bacteria (Rankin et al. 2002), which is absent in strain Lens. In the two other sequenced strains, this region is located between

Novel Coenzyme F420 Dependent Sulfite Reductase and a Small Sulfite Reductase in Methanogenic Archaea

Abstract Recently a novel, highly active, coenzyme F420 dependent sulfite reductase (Fsr) has been discovered in Methanocaldococcus jannaschii. Three other extremophilic methanogens and an uncultured archaeon from a consortium performing anaerobic oxidation of methane (AOM) carry Fsr homologs. Methanogens require sulfide and most are sensitive to sulfite. Since Fsr is induced by sulfite, reduces sulfite to sulfide with H2F420, and seems to be associated with the membrane, it is a sulfite detoxification and assimilation enzyme. The N-terminal half of Fsr is a homolog of H2F420 dehydrogenase (FqoF FpoF). FqoF FpoF is the electron input unit of a membrane-bound electron transport system of late-evolving methylotrophic methanogens and Archaeoglobus fulgidus, a sulfate reducing archaeon employing the partial reverse methanogenesis pathway. The C-terminal half (Fsr-C) represents a dissimilatory sulfite reductase subunit (DsrA). While only four methanogens carry Fsr, every methanogen carries...

Clonidine hydrochloride2 1 and

Dosage and administration expertise is needed to monitor a clonidine detoxification over 1 to 3 weeks. Start clonidine after discontinuation of the opioid. Following a test dose, tablets are given four to six times daily building up to 2 mg daily over a few days in inpatients but half this dose in outpatients. Patches applied once weekly and supplemented by tablets if withdrawal symptoms occur. Frequent monitoring for hypotension and bradycardia is needed.

Functions of Glutathione

In addition to antioxidant effects, glutathione is also needed for the cellular detoxification of noxious compounds, particularly for electrophilic (positively charged) compounds. In this type of detoxification, noxious compounds are joined with glutathione molecules within the cell to form conjugates these have a low reactivity and are easily and safely transported out of the cell. Although liver cells are particularly adept at performing this and other types of detoxification, all cells, including cancer cells, perform detoxification. For example, cancer cells use this detoxification system to export several types of chemotherapy drugs, thereby inducing drug resistance. The enzyme glutathione S-transferase, which catalyzes the conjugation process, is commonly overexpressed in drug-resistant cancer cells. The antioxidant and detoxification actions of glu-tathione are illustrated in Figure 18.1. Glutathione also serves other functions not shown in the figure. High concentrations...

Genetic Susceptibility Genes

A relatively new area of cancer genetics has emerged, involving exploring the question of genetic susceptibility (i.e., given the same level of exposure, why are only certain individuals at risk ). Several genes important in the detoxification of chemical carcinogens are polymorphic in the population, with certain variants resulting in a reduced capacity to metabolize carcinogens these individuals may be at a higher risk of developing cancer.102 Recent studies have explored whether the germline absence of certain genes (e.g., glutathione-S transferase M1, T1), as well as possession of genes that may provide less capability of detoxification (e.g., slow N-acetyltransferase-2 (NAT2) genotype, GSTPi valine variant), may be important risk factors for childhood acute leukemia. Davies et al.,103 in a molecular

Chemicalinduced Carcinogenesis

20.6.1 Phase I Xenobiotic Detoxification 20.6.2 Phase II Xenobiotic Detoxification Bioactive extracts, high in anthocyanins, from the Vaccinium species may have the potential to inhibit the initiation and promotion stages of carcinogenesis under in vitro conditions. Quinone reductase is an enzyme responsible for inactivating electrophilic carcinogens and potentially preventing metabolic activation prior to DNA binding. Crude extracts of the lowbush blueberry, cranberry, lingonberry, and bilberry (Vaccinium) were shown to have the ability to induce the Phase II xenobiotic detoxification enzyme quinone reductase, thus displaying the capacity to inhibit the initiation of chemically induced carcinogenesis.103,104 Extracts were further shown to actively inhibit ornithine decarboxylase, a rate-limiting enzyme in the synthesis of polyamines. Polyamine formation is believed to be associated with carcinogenesis as these compounds are formed in high quantities by rapidly proliferating cells.103

Conclusion and Hypotheses

It is possible that in addition to its assimilatory and detoxification roles, Fsr allows a nonmethanogenic mode of energy generation via H2-dependent sulfite or nitrite reduction in certain methanogens. This system could be a remnant or a precursor of an ancient sulfate reduction pathway. Fsr could also be the ancestor of FqoF FpoF, the electron input unit of the energy-transduction systems in late-evolving archaea, and the subunits of the dissimilatory sulfite reductases. If Fsr is simply a detoxification enzyme, what was its role before the appearance of oxygen on Earth One possible early role of this enzyme is in the synthesis of coenzyme M, where sulfite is the proposed precursor of a sulfonate group (Graham et al. 2002) coenzyme M is essential for methanogenesis. Methanogens lack sulfate reduction enzymes and require sulfide for growth. One way to generate the needed sulfite would be to oxidize sulfide. In the highly reducing, anaerobic environment of early Earth this conversion...

Getting Rid of Dental Toxins

Getting rid of dental toxins is not as simple and straightforward as one might hope. Blood testing to determine what replacement materials are least burdensome to your immune system is available, although not widely. Detoxification after such dental work is also a complex process. When most of the dental toxicity is removed, the spontaneous detoxification of the rest of the body is typically very brisk, needing no detoxification accelerators. Done completely wrong without proper attention to detail, the removal of dental toxins can aggravate your medical conditions. The removal process and the subsequent detoxification process can both be done in either a highly toxic fashion or a safe and only minimally toxic fashion. Thus, it is essential to find a dentist who is well educated on these matters. The last thing you need is a dentist who is just humoring your eccentricities and not paying close attention to the above details. For further help in these matters, see Appendix II at the...

Examples of traditional healing exclusively focused on substance abuse and dependence

Practised by folk healers in northern Mexico, (5Z by the Colorados Indians of Ecuador 40) and by curanderos in northwestern Peru 58) In Thailand, traditional methods of detoxification and rehabilitation of opiate addicts are applied in certain Buddhist monasteries of these Wat Tam Krabok attained international fame. Candidates take a solemn vow of abstention upon admission for the treatment which consists of herbal remedies, hydrotherapy, spiritual-didactic and work-oriented groups. Repeated administration of emetic plant medicines with copious amounts of water, plus herbal steam baths, is purported to clean the addicts from the harmful substances it certainly may lead to collapse, induce an altered state of consciousness, and open the way for personality reorientation in a therapeutic milieu. (59) Comparative case follow-up studies showed that the overall success rates of this Buddhist addiction treatment programme equal those of much more expensive modern medical methods 60' Folk...

Generic Pathway for PLant Response to Stress

A generic stress signal transduction pathway for the plant stress response is depicted in Fig. 24.1. The stress signal is first perceived at the membrane level by the receptors (G-protein-coupled receptors, ion channel, receptorlike kinase, or histidine kinase), which results in the generation of many secondary signal molecules, such as Ca2+, inositol phosphates, ROS, and abscisic acid ABA. The stress signal then transduces inside the nucleus to induce many stress responsive genes, the products of which ultimately lead to plant adaptation to stress tolerance. The stress responsive genes could be either early or delayed induced genes. Early genes are induced within minutes of stress perception, often express transiently, and their products (e.g., various transcription factors) can activate the expression of delayed genes (e.g., RD responsive to dehydration , KIN cold induced , COR cold responsive ). Overall, gene products are either involved directly in cellular protection against the...

Reactive Oxygen Species in Salinity Stress

Superoxide radical (OJ), hydrogen peroxide (H2O2), or a hydroxyl radical (OH-), respectively. The enhanced production of ROIs during stresses can pose a threat to plants because they are unable to detoxify effectively by the ROI scavenging machinery. The unquenched ROIs react spontaneously with organic molecules and cause membrane lipid peroxidation, protein oxidation, enzyme inhibition, and DNA and RNA damage (see Vinocur and Altman, 2005). Oxidative stress arises under environmental stresses, including salinity stress, and may exceed the scavenging capacity of the natural defense system of the plant. The major ROI-scavenging mechanisms of plants include superoxide dismutase, ascorbate peroxidase, catalase, and GSH reductase, which help in the deactivation ofactive oxygen species in multiple redox reactions, thereby contributing to the protective system against oxidative stress. The ROS scavengers can increase the plant resistance to salinity stress. Overexpression of the aldehyde...

Minimize exposure to toxins

Toxins can also rear their ugly head when a well-motivated individual undergoes any of a number of different programs of detoxification, including some that are administered under the guidance of a doctor. Many such programs detoxify too rapidly, and even someone who is practicing the principles of optimal nutrition cannot maintain good health in the face of too-rapid detoxification. This issue is addressed in greater depth in Uninformed Consent.

Bioremediation Activity

In addition to bioremediation of organic compounds, microorganisms have also been implicated in the bioremediation of heavy metals such as selenium, uranium, cadmium and mercury. Metal remediation can be achieved by precipitation and immobilisation of contaminants (microbes can reduce metal which can result in detoxification and precipitation e.g. mercury is taken up into the cell and delivered to the NADPH-dependent flavoenzyme mercuric reductase, which catalyses the reduction of Hg2+ to volatile, low-toxicity HgO Nascimento and Chartone-Souza 2003), by biosorption (passive sequestration by interaction with live or dead biological material bacteria can be genetically engineered to incorporate metal-binding polysaccharides in their cell surface, or to enhance metal transporters with metal binding metallothioneins in the cytoplasm), or by biomineralisation (formation ofinsoluble metal precipitates by interactions with microbial metabolites thus achieving concentration and reduction in...

Application Of Pharmacogenetics In Clinical Gastroenterology And Hepatology

The liver has a complex detoxification system in which several enzymes participate in the metabolism of a large number of xenobiotics. Essentially, all of the major human drug metabolizing enzymes (DMEs) responsible for phase I (modification of functional groups of the xenobiotics) or phase II reactions (conjugation with endogenous substrates) exhibit common polymorphisms at the genomic level (1). The clinical relevance of these polymorphisms depends on how they affect individual susceptibility to disease or response to therapy (efficacy and toxicity). The potential applications of pharmacogenetics in various aspects of clinical gastroenterology and hepatology are summarized in Table 1.

Virulence Factors Genes and Transcription

The P. brasiliensis EST databases were screened for clusters similar to virulence genes from C. albicans and other pathogenic fungi (Goldman et al., 2003 Felipe et al., 2005 Tavares et al., 2005). Although C. albicans might not be the best choice for comparison with P. brasiliensis in terms of fungal biology and disease outcome, it is still the best-studied fungal pathogen, with the relevance of many genes being assessed using gene-directed mutagenesis. Virulence gene homologs have been recognized in groups of metabolic, cell wall, signal transduction, detoxification, and other genes encoding secreted proteins, suggesting that they could be important for P. brasiliensis pathogenesis as well. Another approach to finding virulence-related genes involved detection of differentially expressed transcripts in the yeast phase and during mycelium-to-yeast transition. Large-scale strategies to achieve that purpose included Pb01 database subtraction, macro and microarray hybridization, notably...

Statins as Antioxidants

A critical balance exists between NO and superoxide (O2-). Under physiologic conditions, NO levels are 1,000 times those of O2-, and the normal antioxidant mechanisms are able to detoxify small amounts of reactive oxygen species (ROS). During ischemia-reperfusion and inflammatory disorders, these defenses are overwhelmed and oxidant-mediated injury ensues, including peroxidation of cell membranes, impaired NO bioactivity, induction of leuko-cyte-endothelial adhesion, and thrombosis. Oxidative stress also contributes to the pathogenesis of chronic vascular diseases such as atherosclerosis, diabetes, and hypertension.

Activity Against Toxins

Plant phenolic compounds have also been suggested to provide a means for preventing the adverse affects that fungal toxins (mycotoxins) have on human health as well as serving in their detoxification (Beekrum et al., 2003). These authors investigated the impact of the plant phenolic

Ravindranath R P Kommaddi and H V

Metabolism of foreign compounds is an important prerequisite for detoxification of xe-nobiotics. A major enzyme involved in the metabolism of foreign compounds is cyto-chrome P-450 (P450). Generally, P450 mediated metabolism of xenobiotics leads to the formation of hydrophilic, non-toxic metabolites that are easily excreted from the body. However, there are instances wherein an inert, non-toxic compound is bioactivated to a reactive, toxic metabolite that can interact with cellular macromolecules leading to cell damage. Multiple forms of P450, which are selectively induced or inhibited by a variety of drugs are known to exist in liver, the major organ involved in P450 mediated metabolism (de Montellano, 1996). P450 enzymes, such as CYP2D6 exhibit genetic polymorphism and 7-10 of caucasians are poor metabolizers of debrisoquine (prototype substrates for P4502D6) while the remaining 90 are extensive metabolizers. The significance of P450 metabolism in extrahepatic organs (such as lung,...

Fluorescent Sensors for Ratiometric Detection of Zinc


FuraZin-1 (78, Figure 21) is a Zn2+-responsive Fura-2 analogue that exhibits an excitation wavelength shift from 378 to 330 nm in the presence of increasing Zn2+ concentrations 222 . This excitation-ratiometric probe has an emission maximum at 510 nm. IndoZin-1 (79, Figure 21) is a Zn2+-responsive Indo-1 analogue that shows an emission wavelength shift from 480 to 395 nm with increasing amounts of Zn2+ 222 . This emission-ratiometric probe has an excitation maximum at 350 nm. Both sensors exhibit moderate affinity for Zn2+ (Kd 3.4 M for 78, 3.0 M for 79) and good selectivity over cellular concentrations of Ca2+ and Mg2+ .FuraZin-1 has been used to monitor Zn2+ levels in yeast cells and has helped clarify the role of the ZRC1 protein in storage and detoxification of excess Zn2+ during Zn2+ shock 227 . In a similar approach, DPA-based ligands have been coupled to benzofuran and fura chromophores to produce ZnAF-R1 (80, Figure 21) and ZnAF-R2 (81, Figure 21), respectively 228 . ZnAF-R2...

Transport Trafficking and Homeostasis

The metallothioneins (MTs) are another vital class of proteins involved in zinc metalloneurochemistry 2,79-81 . These cysteine-rich proteins have several functions in the brain and CNS, including detoxification of heavy-metal contaminants 62,81,82 and protection against oxidative stress 79,83-85 . MT-1 and MT-2 are expressed in all mammalian tissues 79,80 , and MT-3 is a brain-specific member of this family, which is particularly abundant in zinc-enriched neurons 86 . MT-3 coordinates seven Zn2+ ions under normal conditions and maintains its cluster structure with fewer than seven ions bound 87 . Metal ion binding proceeds in a noncooperative manner, and MT-3 can house up to nine Zn2+ ions. MTs provide some of the most thermodynamically stable Zn2+ sites in eukaryotes with dissociation constants on the order of Kd 0.1 pM, yet they can exchange Zn2+ readily with proteins having weaker Zn2+ affinities 79,88,89 . By comparison, carbonic anhydrase (CA), which also binds Zn2+ tightly with...

Toxicokinetics and Mechanism of Action

Lead has also been suggested to possibly perturb glucocorticoid-mediated events in the central nervous system hormonal target tissues 78 . Glucocorticoid receptors are widespread in neurons and glial cells and are known to modulate glial cell functions such as synthesis of myelin phosphatide precursors by glyc-erol phosphate dehydrogenase, amidation of the neurotransmitter glutamate, and detoxification of ammonia by glutamine synthetase. Tonner and Heiman 78 found that addition of lead acetate to C6 glioma cells in vitro resulted in a significant reduction of the binding affinity of glucocorticoids for cytosolic receptors. High-affinity cytosolic lead-binding proteins have been identified in the brain (and kidneys) of rats. These high-affinity zinc- and lead-binding proteins are thought to moderate lead inhibition of 8-aminolevulinic acid hydratase (ALAD) through lead chelation and zinc donation, and to translocate lead to the nucleus, where it may influence gene expression. Similar...

Mapping And Cloning Of Prkn

There is still relatively little information available on the neuropathology of molecularly confirmed cases of parkin-related AR-JP. Severe and selective degeneration of dopaminergic neurons and gliosis in the substantia nigra pars compacta and, to a somewhat lesser degree, of the locus coeruleus, has been described.39-41 Lewy bodies or other alpha-synuclein-containing Lewy-pathology have usually not been described, suggesting that the disease process probably differs in some important ways from that of typical idiopathic PD. This is further supported by the finding of neurofibrillary tangles and tau-pathology in the brains of patients with parkin disease, a feature that is usually not associated with LB-positive PD. Lewy bodies are thought to represent a mechanism whereby cells sequester damaged and toxic proteins in an inactive form. The ubiquitine-proteasome system (UPS) is involved in the detoxification of these proteins, so complete loss of parkin (a component of the UPS-see...

Healing Powers Of Secretions History Of Breastfeeding

It is now well established that bifidobacteria predominate in the feces of the breast-milk-fed infant. Human, but not cow's, milk contains factors that stimulate colonization with bifidobacteria. This observation was largely possible because of the discovery in 1953 of Bifidobacterium bifidum, a subspecies of bifidobacteria that requires human milk for its growth. Over the years, bifidobacterium has been used anec-dotally and more recently under controlled conditions as a therapeutic modality to prevent and treat diarrheal disease, induce immunomodulation, detoxify the gastrointestinal

Toxic Derivatives of Oxygen O2

Cell Called Shrinkage

Although not toxic itself, O2 can be converted into a number of compounds that are highly toxic. Some of these, such as superoxide (O2 ), are produced both as a part of normal metabolic processes and as chemical reactions involving oxygen and light. Others, such as hydrogen peroxide (H2O2), result from metabolic processes involving oxygen. To survive in an environment containing O2, cells must have enzymes that can convert these toxic compounds to non-toxic forms. The enzyme superoxide dismu-tase degrades superoxide to produce hydrogen peroxide. Catalase breaks down hydrogen peroxide to H2O and O2. Together, these two enzymes detoxify these reactive products of O2.

How might P falciparum cause this complex disease

Researchers are also becoming aware that, beyond energy production, mitochondria also play a vital role in cell homeostasis through generation and detoxification of reactive oxygen species 107 . The accelerated oxida-tive damage that accompanies sepsis could be both a cause and a consequence of cytokine-induced mitochondrial dysfunction. Interestingly, the ultrastructural damage reported to accompany mitochondrial dysfunction in sepsis 102 reflects Maegraith's observations in monkey malaria 108110 decades ago.

Structures That Enable Internalization

Hydathodes, apparently designed to release excessive water pressure in the plant, vary in complexity among different plant species but all provide a connection between the water-conducting elements and the external environment 18 . Certain ones resemble stomata except for not closing during darkness. Others are specialized for water release and may be better termed water glands.'' Gas exchange could occur through hydathodes that are not water congested. Water congestion develops in above-ground tissues of plants when the roots absorb water more rapidly than above-ground parts lose it to evapotranspiration 25 . The excess water can pool under the epidermis causing edemas or, more often, water moves from the ends of the vascular strands through the leaf mesophyll and then into and out of hyda-thodes in a process called guttation 21 . Guttation droplets, which are derived from xylem sap, appear on the edges of leaves and are often confused with dew. However, guttation may occur at any...

Laccase Based Defense Against Biological and Chemical Warfare Agents

Nerve agents such as organophosphorus compounds are strong inhibitors of acetylcholinesterase, which binds and hydrolyzes the neurotransmitter acetylcholine. The inhibition can result in convulsions, salivary secretion, behavioral incapacitation, muscle weakness, and ultimately death due to respiratory failure. The application of hydrolytic enzymes to detoxify organophosphorus-based chemical nerve agents has been under investigation for decades, as the huge stockpiles of about 200 000 tonnes of nerve agents worldwide is a great international concern. Since the early work on the ability of mammalian tissue to hydrolyze diisopropyl fluorophosphates, a variety of hydrolytic enzymes with activity on organophosphorus compounds have been identified, purified, and characterized from sources such as mammals, cephalopods, and microorganisms. Reports on oxidative degradation of nerve agents by enzymes are more recent. A fungal laccase has been demonstrated to be capable of degrading VX 188 ,...

Microvascular Actions of CO

Hifas Aseptadas

CO is a gaseous product of the HO reaction that utilizes molecular oxygen to oxidatively degrade protoheme IX into biliverdin-IXa, ferrous iron, and the gas. CO has been considered a gaseous mediator analogous to NO that activates soluble guanylate cyclase (sGC) as a common transducer to relax vascular systems. In mammals, HO exists in two forms HO-1 and HO-2. HO-1 is induced by varied stressors such as cytokines, heavy metals, ROS and hypoxia. Excess NO could also cause the HO-1 induction. Microvascular actions of endogenously generated CO was first demonstrated in the liver 10 . Liver constitutes a major organ responsible for detoxification of the hemoglobin-derived heme and biliary excretion of bilirubin-IXa, a product generated from biliverdin-IXa through biliverdin reductase. We

Association of Polymorphisms in DME and Drug Transporters with Disease Susceptibility and Progression

Biliverdin Ixa

Epoxide hydrolase catalyzes the irreversible hydration of highly reactive alkene epoxides and arene oxides generated by CYP450-dependent oxidation to yield metabolites that can be readily conjugated and excreted (24). In the liver, the distribution of epoxide hydrolase parallels that of CYP450 being located in the centrilobular region (zone 3). The enzyme plays an important role in detoxifying electrophilic epoxides that might otherwise bind to proteins and nucleic acids and cause cellular toxicity and genetic mutation. Micro-somal epoxide hydroxylase (mEH) is involved in the metabolism of a wide variety of xenobiotics and has been found in virtually all tissues, including liver, kidney, lung, and testis (25). Two point mutations in exons 3 and 4 lead to the amino acid changes, Tyr113His and His139Arg, respectively, which affect mEH activity by influencing protein stability (26,27). In a study involving 394 patients at different stages of HCV-related liver disease, patients homozygous...

Ecogenetics The Study of Gene Environment Interactions Daniel W Nebert Amy L Roe PhD

Around 1930-1970, DMEs were considered as a liver detoxification system responsible for breaking down drugs and other hydrophobic environmental chemicals for excretion. It is now clear that (1) at least some of these DMEs are located in every eukaryotic cell, (2) almost all DMEs have endogenous compounds as their natural substrates, and (3) many of these DMEs have existed in evolution prior to the divergence of bacteria from eukaryotes, indicating that these DMEs have been responsible for critical life functions long before animal-plant divergence (8, 9). Since the late 1940s, it has been taught that drug and carcinogen metabolism is carried out by phase I (functionalization) and phase II (conjugation) reactions (Fig. 7.5). Originally, these two coupled reactions were regarded simply as a liver detoxification system. In the 1960s, some of these activities were then discovered in nonhepatic tissues such as lung, kidney, and gastrointestinal tract indicating that the activities were not...

The Hyperoxidation Of Peroxiredoxins

Early studies on oxidative stress in yeast revealed that a 25kDa protein called thiol specific antioxidant protein (TSA) was able to protect glutamate synthetase from inactivation in the presence of Fe3+, O2 and dithiothreitol (DTT) (Kim et al 1985). TSA was later shown to belong to the ubiquitous peroxiredoxin family (Chae et al., 1994) that uses redox-sensitive cysteine residues to detoxify hydrogen peroxide, lipid hydroperoxides and peroxynitrite. As a result of kinetic studies that showed TSA receives reducing equivalents from the NADPH thioredoxin reductase thioredoxin system to break down hydrogen peroxide, tert-butyl peroxide and cumene peroxide, TSA was renamed thioredoxin peroxidase (TPx) (Chae et al., 1999). The rate of peroxide removal was initially fast and decreased gradually when 1 mM H2O2 was used as the substrate (Chae et al., 1994). However, 5mM H2O2 caused a marked decrease in the rate of peroxide consumption. Substrate inactivation was also more rapid with t-butyl...

Selenocompounds In Plants And Animals

The four GPXs are located in different parts of tissues and all detoxify hydrogen peroxide and fatty acid-derived hydroperoxides and thus are considered antioxidant selenoenzymes. The three deiodinases convert thyroxine to triiodot-hyronine, thus regulating thyroid hormone metabolism. The thioredoxin reduc-tases reduce intramolecular disulfide bonds and, among other reactions, regenerate vitamin C from its oxidized state. These reductases can also affect the redox regulation of a variety of factors, including ribonucleotide reductase, the gluco-corticoid receptor, and the transcription factors.13 Selenophosphate synthetase

Underlying Chemopreventive Mechanisms Of Vitamin C

The intrinsic pro-oxidant potential of vitamin C may also contribute to its chemopreventive properties. A low or baseline level of oxidative stress appears to be essential for the cellular transduction signals that lead to the induction or potentiation of some detoxification antioxidant enzyme systems. Antioxidant micronutrients may act as mild pro-oxidants to supply limited amounts of ROS when needed for triggering antioxidant signal transduction. If this is the case, it remains to be clarified when and how the pro-oxidant activity of vitamin C is turned on in the intracellular redox milieu while it is fighting, as an antioxidant, against excess oxidative stress.

Evolution Of Xenobiotic Metabolism In Humans

Xenobiotics Metabolism Liver

Another source of variability germane to this treatise is that the genes that code for xenobiotic metabolizing enzymes can exist in polymorphic form, with multiple allelic variants determining the human phenotype for this detoxification process. It therefore seems likely that genetic variability in the capacity to metabolize xenobi-otics, including carcinogenic molecules, may be related to enzyme systems such as those involving cytochrome P450 (CYP450), glutathione S-transferase, and N-acetyltransferase gene families (77). As an example, polymorphic alleles carrying multiple active gene copies exist for CYP450 and, in the case of CYP2D6, are thought to be directed by positive selection due to development of alkaloid resistance by humans living in northeast Africa about 10,000-5000 BC (78). Although evolution has preserved CYP2D genes in rodents, inactivation has occurred in humans. Hence mice have nine active genes at this locus, but humans only have one....

Microbiology of Bioremediation

Bioremediation is the use of biological agents such as bacteria and fungi to degrade or detoxify pollutants in a given environment. It may involve the use of specific organisms introduced into the polluted environment or, more commonly, it may take advantage of organisms already present, possibly adding nutrients to encourage their growth.

Arthropod resistance to synthetic and natural insecticides and acaricides

4 Metabolic resistance, where the metabolic pathways of the insect become modified in ways that detoxify the insecticide, or disallow metabolism of the applied compound into its toxic form. The most important mechanisms of metabolic resistance involve multifunction oxidases, glutathione-S-transferase, and esterases in the case of pyrethroids (which are almost all esters). In general, site-insensitivity or metabolic detoxification are the main resistance mechanisms, and physiological resistance can be seen as resulting from an interplay of these factors (Miller 1988). Use of synergists if feasible. These chemicals inhibit specific detoxification enzymes and thereby reduce the selective advantage of arthropods that have such enzymes.

Relevance Of Alcohol Withdrawal Seizures In Rodents To The Human Condition

Neuronal plasticity mechanisms may play a role in the susceptibility to alcohol withdrawal seizures in humans and rodents. In humans the number of detoxifications, not the absolute amount of alcohol intake, best predicts the likelihood of subsequent alcohol withdrawal seizures (Ballenger and Post, 1978). Similarly studies in rodents have shown that repeated alcohol withdrawal experiences increase the severity and duration of subsequent withdrawal seizures. For example, this was the case in the study of Becker and Hale (1993) in which adult male mice were chronically exposed to ethanol vapor by inhalation. Animals in a multiple withdrawal group experienced three 16-hour exposure periods separated by 8-hour periods of abstinence a single withdrawal group received a single 16-hour bout of ethanol exposure. The severity of HIC was significantly greater in the multiple withdrawal group than in the single withdrawal group. In additional studies, mice experiencing multiple withdrawal...

Bile Acid Composition Of Various Species

In relation to the importance of bile acids in host defence against endotoxins one may ask the question whether or not bile composition plays a role in the endotoxin sensitivity resistance of various species 45 , We have observed earlier that there are major differences in bile acid composition of bile obtained from sensitive (e.g., man, cow, guinea pig) and resistant species (e.g., birds, fish) 39 , It is interesting to note that there is a direct correlation between endotoxin sensitivity and radiation sensitivity of various species. Perhaps the ontogeny of the production of bile acids in chickens bears relevance to the fact that chicken embryos show endotoxin sensitivity up to 11 days of age, which is the time of the initiation of bile acid synthesis in the liver. Older chicks or mature animals can only be made susceptible to endotoxin by lead acetate treatment. It is likely that bile acids function not only in the gut but also in the liver in addition to acyloxyacyl hydrolase...

Other Pharmacogenetic Markers Of Interest Drug Transporter Polymorphism

Uptake, distribution, and excretion of endogenous and exogenous compounds including antibiotics is controlled by polyspecific membrane transporters expressed in intestine, liver, kidney, placenta, testis, blood cells and the endothelial cell lining of brain capillaries, where they constitute the blood-brain barrier. Increasingly, membrane-spanning proteins involved in the inward or outward transport of a large variety of drugs have been recognized and characterized over the past years in almost all tissues (Table 2). Drug transporters can be viewed as completing the enzyme-based detoxification systems to achieve efficient protection against chemical toxins. Both systems show similar broad specificity and may even work in synergy. Drug uptake delivers the drug to the detoxification system facilitating metabolism, and drug efflux decreases the load on detoxification enzymes, thereby avoiding their saturation, while chemical modification, which usually increases the amphiphilicity of...

[1 UDPGlucuronosyltransferases Gene Structures of UGT1 and UGT2 Families

Ugt1 Family

In human, rat, and mice, a UGT1 complex locus provides for developmental-, inducer-, and cell-specific synthesis of a family of chemical-detoxifying isozymes, UDP-glucuronosyltransferases, which prevent toxicities, mutagenesis, and or carcinogenesis. Between 10 and 14 first exons with individual promoter elements are tandemly arrayed upstream of 4 shared exons so as to synthesize independently as many overlapping primary transcripts. RNA splice sites allow a lead exon to join the common exons to generate mRNAs with unique 5' ends, but common 3' ends. Intra- and interspecies comparisons of amino acid sequences encoded by first exons show an evolutionary continuum also, recognizable bilirubin- and phenol-specific catalytic units are differentially regulated by model compounds, phenobarbital, and or aromatic hydrocarbons. Whereas UGT1 loci allow minimal changes to achieve new isozymes, a single deleterious mutation in a common exon negatively impacts the arrangement by inactivating the...

Endoplasmic Reticulum

Golgi Apparatus

The smooth ER lacks ribosomes and thus has a smooth appearance. Most cells contain very little smooth ER. Smooth ER builds lipids such as cholesterol. In the ovaries and testes, smooth ER produces the steroid hormones estrogen and testosterone. In skeletal and heart muscle cells, smooth ER releases calcium, which stimulates contraction. Smooth ER is also abundant in liver and kidney cells, where it helps detoxify drugs and poisons. Long-term abuse of alcohol and other drugs causes these cells to produce more smooth ER. Increased amounts of smooth ER in liver cells is one of the factors that can lead to drug tolerance. As Figure 4-15 shows, rough ER and smooth ER form an interconnected network.

Pharmacology and Mechanism of Action

Azathiprine Allopuyrinol

Figure 3 The metabolic pathway involved in the detoxification of azathioprine 6-MP. TPMT is a key enzyme (gray boxes) in which polymorphic variability can result in an increased risk of azathioprine toxicity. Abbreviations HGPRT, hypoxanthine guanine phosphoribosyltransferase MP, mercaptopurine TPMT, thiopurine methyltransferase. Figure 3 The metabolic pathway involved in the detoxification of azathioprine 6-MP. TPMT is a key enzyme (gray boxes) in which polymorphic variability can result in an increased risk of azathioprine toxicity. Abbreviations HGPRT, hypoxanthine guanine phosphoribosyltransferase MP, mercaptopurine TPMT, thiopurine methyltransferase.

Metabolic Therapies Gerson and Gonzalez

Metabolic therapies are based on the belief that cancer is a symptom of the accumulation of toxins. The aim of treatment is therefore detoxification using coffee enemas or high colonics, special diets, raw juices, enzymes, and supplements. A retrospective study of melanoma patients treated by Gerson therapy, conducted by physicians working at the clinic where study patients were treated, concluded that 5-year survival of patients receiving Gerson therapy was higher than reported in large cohort studies.27 This analysis was flawed by the use of unadjusted comparisons to nonrandomized controls and the exclusion of 40 of the Gerson therapy patients from analysis. In response to detailed criticisms, the authors accepted that a nonrandomized study such as the one published did not provide strong evidence of a treatment effect.28 A more promising result has been reported from a cohort study of 11 pancreatic cancer patients treated by Nicholas Gonzalez using

Monitoring supplementation

A further consideration is especially important when the patient is detoxifying rapidly, as often occurs after dental toxicity has been removed. Sometimes the very minerals that restore clinical health also increase the rate at which cells can release their stored toxins. Such a detoxification also involves retoxification, since all released toxins do not get completely excreted. Some of them are redeposited into new cells, producing a new toxic effect in those cells. This possibility should always be considered when there is a return of symptomatology in a patient who initially responded very well. Detoxification must always proceed at a relatively slow, controlled rate, so that any retoxification will be adequately neutralized by an immune system well supported with optimal nutrition and optimal supplementation, such as megadose vitamin C. and you should attempt to get your chemistries to move toward this level of normalcy rather than away from it. These tests are especially...

Applications of the Drosophila aSynuclein Model

Of PD individuals, particularly at serine residue 129, and that the phosphorylation status of a-synuclein influences its propensity to form aggregates in vitro (45,46). Interestingly, the phosphorylation of a-synuclein at Ser129 appears to be conserved in Drosophila (47). To explore the consequence of Ser129 phosphorylation on aggregate formation and neuronal integrity Chen and Feany (48) generated mutationally altered a-synuclein transgenic constructs consisting of a Ser129 to Ala (S129A) mutation to prevent phosphorylation and a Ser129 to Asp (S129D) mutation to mimic the phosphorylated state. They expressed these transgenic constructs in the Drosophila nervous system and compared the extent and timing of pathology in these lines to flies expressing WT a-synuclein. In agreement with previous work, WT a-synuclein protein was found to be phosphorylated at Ser129, whereas the mutationally altered a-synuclein proteins lacked this modification. Further studies demonstrated that...

Importance Of Srx In Cell Signalling And Defense

2-Cys Prxs also detoxify peroxides within the chloroplast (Dietz et al., 2002 K nig et al., 2002). The chloroplast is the main source of ROS due to its role in photosynthesis and the synthesis of amino acids, fatty acids and nucleotides (Apel et al., 2004). Given the importance of Prxs in plants, the molecular and functional characterization of Arabidopsis and rice Srx was investigated (Liu et al., 2006). As shown in Fig. 2, Arabidopsis Srx (AtSrx) contains all the conserved residues

Mechanisms Of Antioxidant Defense By Flavonoids

A mechanism of great importance in antioxidant defense, detoxification, and cancer prevention is the induction of phase 2 enzymes. Evidence of this important in vivo response to bioflavonoids is from cell, animal, and human studies. Figure 2 illustrates the major pathways of phase 2 enzyme induction. Phase 2 enzyme induction results in synthesis of flavonol and other conjugation enzymes. Major flavonol conjugation enzymes are Glutathione as in GSH S-tranferases Glucuronic acid as in UDP-glucuronosyltransferases Methylation as with methyl transferases Sulfation as sulfotranferases. All cells possess elaborate antioxidant defense systems that consist of interacting micronutrients, enzymes, and other molecules. Oxidants such as hydroperoxides (H2O2, CH3OOH, ROOH), many natural antioxidant substances, and a broad range of chemicals reacting with sulfydryl groups induce phase 2 enzymes. Phase 2 enzymes protect against oxidants and electrophilic toxicity, i.e., antioxidant defense,...

Regulation Of Natural Immunity

Endotoxin injections produce endotoxin tolerance and elevate natural resistance. However, such injections may have serious side effects, such as high fever, hypotension and abortion. For this reason LPS injections are not suitable for the enhancement of natural immune mechanisms in endotoxin-sensitive mammalian species. Various techniques have been used (physical, chemical, etc.) for the detoxification of endotoxins while the beneficial effects were maintained. One of the best detoxification techniques is treatment with ionizing radiation. The irradiation of LPS with 60Co (100-200 kGy) decreased its toxicity. Such radiodetoxified endotoxin (RD-LPS) preparations showed decreased toxicity, whereas the beneficial effects were preserved (150 kGy TOLERIN(R)). Irradiation causes marked chemical alteration in LPS, such as the decrease of glucosamine, KDO and fatty acids. A single parenteral injection of TOLERIN is capable of preventing various shock syndromes in experimental animals. Unlike...

Neurological involvement in malaria

In the brain, mitochondrial function may also be influenced by neuronal excitotoxins. Within the simplified model of dissociated neuronal culture, mitochondria appear to play a critical role in neuronal homeostasis during excitotoxin exposure. Mitochondria are not only involved with maintaining ATP production but also calcium homeostasis, and generation and detoxification of reactive oxygen species 107 . Excitotoxin production may also be influenced by cytokine release. TNF administration has been shown to alter brain metabolism of tryptophan to produce more kynurinine 159, 160 . Thus, as part of a general inflammatory reaction, increased excitotoxin generation during acute malaria may contribute to cellular energy imbalance. Elevated levels of neuronal excitotoxins (quinolinic and picolinic acid) in the CSF have been associated with a fatal outcome in Malawian children with CM 161 . Similarly, a graded increment of quinolinic acid concentration in CSF was observed across patient...

Pharmacological interventions for opiate users maintenance and withdrawal

Oral methadone is a cost-effective treatment either as outpatient maintenance or as a means of in- or outpatient detoxification through dose reduction. Studies suggest that a minimum effective dose in excess of 60 mg day is required to optimize the benefit from maintenance treatment (recommended doses for substitute prescribing are above 50 mg day), and significantly higher doses will be used in the treatment of many addicts (usual range 40-100 mg day). However, it must be remembered that these doses are potentially fatal if taken by individuals without tolerance to the effects of opiate drugs. Although a slow reduction in the dose of a full agonist (or a partial agonist such as buprenorphine) may be used to detoxify dependent users, other methods are now available. The a2 agonists clonidine and lofexidine may also be used to alleviate the distress associated with the central noradrenergic hyperactivity that is responsible for many of the symptoms of opiate withdrawal. The dose of...

Therapy Of Increased Homocysteine Levels In Pd Patients

Putative therapeutic approaches for the reduction of homocysteine levels are additional folic acid supplementation, since folic acid catalyzes and enhances metabolism of homocysteine to methionine and then S-adenosylmethionine or vitamin B complex administration or the application of COMT inhibitors as adjuncts to levodopa DDI treatment (39,48,62,63). On the one hand, peripherally acting COMT inhibitors increase the bioavailability of levodopa, but on the other hand combination of levodopa DDI with COMT inhibitors reduces O-methylation of levodopa and thus may decrease homocys-teine levels in the periphery (34,64). Central COMT activation causes sustained synthesis of homocysteine in astrocytes and transport of this amino acid to neurons, which was blocked by COMT inhibition with corresponding neuroprotective effects (53,65,66). But this approach may cover only one aspect of the whole issue, since centrally acting COMT inhibitors, i.e. the recently relaunched tolcapone, reduce the...

EFruits and Vegetables

Fruits and vegetables are readily available in developed countries and are a natural source of nutrients, fiber, and potent antioxidants. During an intervention assay the amount of DNA damage in the peripheral lymphocytes of test subjects was substantially reduced. Thus, the number of mutations can be reduced, as well as the possibility of developing tumors.29 Fruits and vegetables may be up to 20 d.w. of the diet of vegetarians, which includes high levels of phenolics. Some phenolics have been considered as trapping agents of nitrates, preventing the formation of the mutagenic N-nitroso compounds, which in turn have been linked to cancers of the nasopharynx, esophagus, and stomach. Additionally, phenolics are part of the detoxification systems.30 Currently, blueberries are emerging as one of the brightest prospects among fruits. Products from blueberries and other Vaccinium sp. can be marketed as dietary supplements in the United States with a structure-function claim such as promote...

Susceptibility Genes In Neurodegeneration

Methylenetetrahydrofolate reductase gene (MTHFR), have been tested as risk factors for the occurrence of AD however, despite some associations and interactions with the APOE genotype being observed (61), results are still controversial (62). Long-term inflammation is a risk factor for AD, and associations between genes encoding for members of the inter-leukin (IL) family, particularly IL-1a, and AD have been observed (63). Several chemicals require metabolic activation to exert their toxic effect, so that polymorphisms in genes encoding for enzymes involved either in the phase I or in the phase II of the metabolic processes, have been extensively tested as possible susceptibility factors in neurodegener-ative disorders. Cytochrome P450 iso-enzymes (CYPs) are involved in phase I, they add a molecule of oxygen to the parent molecule leading to the formation of an intermediate, which can then react with phase II enzymes such as glutathione S-transferases (GSTs) or N-acetyltransferases...

The Importance Of Cholesterol In The Diet

From the brisk detoxification typically seen in such patients. In any event, the observation was so reliable that patients who did not want to eat any meat at all were discouraged from even undergoing the dental revision. Whenever a patient invests time, money, and some degree of suffering in a dental and lifestyle treatment plan, they want to get better. And when they don't get better, they get upset and want to blame someone other than themselves. Both doctor and patient want to avoid such a situation from ever occurring. A vegetarian who won't convert may benefit from the removal of highly toxic dental infections, such as root canals, but the rate of detoxification typically seen after a Total Dental Revision will often overwhelm the limited toxin-neutralizing capacity of exclusively vegetarian-based nutrition.

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