Detoxification and Cleansing Programs

Detoxification and Weight Loss

Detoxification and Weight Loss

Detoxification is something that is very important to the body, but it is something that isn't understood well. Centuries ago, health masters in the East understood the importance of balancing and detoxifying the body. It's something that Western medicine is only beginning to understand.

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7 Day Raw Detox

The 7 Day Raw Detox is a vegan 7 day detox which means no consumption of processed foods (unless processed by you) no cooked food of any kind and nothing that originates from a living creature including any animals or insects. This includes no alcohol, coffee, meat, eggs, cheese, dairy, sugar, cereal, bread pasta, rice, packet food or anything perserved through a cooking method of any kind. You will be provided with all the recipes, shopping lists, templates, meal planners and more you need to organize your shopping and food for your detox. You will also be invited to join a Vip Support Group on Facebook with other Detox participants with daily motivation and support by the detox crew.

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Group of Proteins Involved in Drug Detoxification

The glutathione-related detoxification pathway is commonly discussed as one of the major mechanisms of MDR. GSH and the associated enzymes glutathione S-transferases, peroxidases, and reductase, have frequently been implicated in chemoresistance 54-56 . Glutathione reductase was differentially overexpressed in several chemoresistant variants of the human melanoma cell line MeWo. This enzyme maintains high levels of reduced GSH in the cytosol and may therefore act as an indirect marker for GSH concentration.

Vegetables and Fruits

Vegetables and fruits are the cornerstones of a healthy diet. They are rich sources of vitamins, minerals, complex carbohydrates, and fiber. Some, such as peas and corn, are also good sources of protein. Moreover, vegetables and fruits are generally inexpensive, contain no cholesterol, have little or no fat, and are low in calories. A high intake of vegetables, particularly of the Brassica family (broccoli, cabbage, cauliflower, and Brussels sprouts) can sharply reduce the risk of cancer.10 These vegetables contain compounds that can help the body detoxify and clear potential carcinogens. In addition, fruits and vegetables are rich sources of antioxidant nutrients, such as beta carotene and vitamin C, that may also protect against cancer and heart disease.2122

Therapeutic Potential Of Nscs

The inherent biologic properties of NSCs may circumvent limitations of other techniques for treating metabolic, degenerative, or other widespread lesions in the brain. They are easy to administer (often directly into the cerebral ventricles), are readily engraftable, and circumvent the blood-brain barrier. Unlike BMT, a preconditioning regime is not required before administration (e.g., total-body irradiation). One important property of NSCs is their apparent ability to develop into integral cytoarchitectural components (47) of many regions throughout the host brain as neurons, astrocytes, oligodendrocytes, and even incompletely differentiated, but quiescent, progenitors. Therefore, they may be able to replace a range of missing or dysfunctional neural cell types. A given NSC clone can give rise to multiple cell types within the same region. This is important in the likely situation where return of function may require the reconstitution of the whole milieu of a given region, e.g.,...

In Vivo Versus In Vitro Studies

With regard to the structural and functional multiplicity of mammalian drug-metabolizing enzymes and the genetic and environmental factors that affect their expression. The role of these enzymes in drug metabolism and detoxification and the increased availability of human tissues have also stimulated the development of in-vitro systems, as has the actions of animal rights activists against the use of animals for drug development and toxicological studies.

Consequences of Altered Glucose Metabolism Oxidative Stress

Reactive oxygen species, if not detoxified by the antioxidant systems, exert a toxic action on polyunsaturated fatty acids, circulating proteins, proteins of cell surface, enzymes and nucleic acid (DNA), leading to irreversible damage of cell structure and functions. Thus, an adequate presence and functioning of antioxidant systems is paramount for cell activity. In advanced cancer patients the high levels of ROS are caused by 2. An inadequate detoxification due to altered glucose metabolism in addition to symptoms such as anorexia cachexia, nausea, and vomiting, that prevent a normal nutrition and thereby a normal supply of nutrients such as glucose, proteins and vitamins, leading to accumulation of ROS 53 . In a series of our recently published studies

The Abcc Cftrmrp Subfamily

Which in turn control opening and closing of the chloride channel 88 . Mutations in ABCC7 (CFTR) cause cystic fibrosis by affecting numerous secretion processes. ABCC1, ABCC2, and ABCC3 are all able to transport anticancer drugs, whereby ABCC1 (MRP1) mainly transports glutathione-conjugated (GSH) molecules and therefore has been termed GS-X pump 89 . In addition to cancer drug resistance, the physiologic function of GS-X pumps is closely related with cellular detoxification, oxidative stress, and inflammation 90 .

Strategies To Overcome Resstance

One example of a well-characterized polymorphism in drug metabolism that is currently used to screen patients treated with thiopurines is the SNPs present in thiopurine methyltransferase. 6-Mercaptopurine is a thiol-substituted analog of hypoxanthine, used to treat patients with acute lymphoblastic leukemia. TPMT methylates both the parent compound (6-MP) and the active phosphorylated metabolites of 6-MP, resulting in detoxification of the compound. Patients with homozygous mutations in (G238C) (TPMT*2) or (G460A and A719G) (TPMT*3A) experience profound neutropenia when exposed to thiopurines (52-54). Heterozygotesfor these auto-codominant mutations experience intermediate toxicity, with as many as one-third of these patients requiring a dose-reduction of thiopurines during therapy for ALL (55). Therefore, these somatic mutations alter the ability of patients to receive maximal doses potentially altering outcome in some studies.

Use in Prevention and Therapy

Protection from adverse effects of environmental chemicals and drugs. Molybdenum is a cofactor in enzymes that provide antioxi-dant protection and help the liver detoxify foreign compounds. Thus, increasing molybdenum intake may help protect against damage during exposure to environmental chemicals and drugs.1,2

Multidrug Resistance ABCB1MDR1 ABCC1MRP1 ABCG2

When cells are exposed to toxic compounds, as is the case for tumor cells treated with chemotherapy, resistance against these drugs can occur by a variety of mechanisms. Among these are decreased cellular uptake, increased intracellular detoxification, modification of target proteins, and enhanced extrusion from cells. Although in most cases one compound initially causes these events, cells can become resistant to a variety of drugs with structural similarities to the initial compound. This multidrug resistance (MDR) is mainly caused by three drug efflux pumps, ABCB1 (MDR1), ABCC1 (MRP1), and ABCG2 (MXR, ABCP, BCRP) (Tabs 3.1 and 3.2).

Clinical Correlation

Testinal system diffuse into the hepatocytes via sinusoidal membranes, where metabolic processes involving proteins, fats, carbohydrates, vitamins, and detoxification occur. The central veins receive the sinuosoidal flow of fluids, which eventually move to the hepatic vein for outflow to the venous circulation. Lymphatic vessels also play a role in removing fluids from the liver. Small bile ducts, or biliary canaliculi, are also a part of the lobule and are responsible for carrying the bile out of the liver and eventually to the common bile duct and duodenum.2 Hepatocytes are highly organized cells with active organelles, including endoplasmic reticulum, Golgi complex, lysosomes, mitochondria, and microtubules. The smooth endoplasmic reticulum is the site of hepatic drug metabolism, drug detoxification, bilirubin conjugation, and cholesterol synthesis. The rough endo-plasmic reticulum with ribosomal complexes is the site for albumin, enzyme, coagulation factor, and other protein...

Pharmacokinetic and ADME Studies

A large number of the drug metabolizing enzymes found in the subcellular fractions have been purified and characterized. Of the human enzymes involved in drug metabolism, the cytochromes P450, which constitute a superfamily of hemoproteins, have been the most widely studied. Over 200 P450 genes have been classified on the basis of structure into 36 gene families. Twelve of these gene families exist in all mammals examined to date, and three of these families, CYP1, CYP2, and CYP3, are thought to be responsible for the majority of hepatic xenobiotic metabolism. Under many conditions, a single P450 may be exclusively or primarily responsible for the detoxification or bioactivation of a particular compound (62). A major disadvantage of using purified enzymes is the amount of work required to prepare sufficient quantities of the enzymes needed to carry out studies. However, the availability of the cDNA for specific isozymes of human cytochromes P450 has made the production of large...

Cysteine and Glutathione

Antioxidant and detoxification function. Cysteine, alone or as part of glutathione, is a potent antioxidant, protecting against free radical damage.2 Glutathione, working with the enzyme glutathione peroxidase (a selenium-containing enzyme), detoxifies free radicals, drugs, and toxic chemicals. It also recycles oxidized vitamin E and vitamin C, conserving body stores of these antioxidants.3

Recommended Daily Intakes

Recommended doses for L-cysteine are in the range of 500-1500 mg day. if the primary aim of therapy is increasing glutathione levels, cysteine should be supplemented with glu-tamine and selenium. Selenium supports optimum functioning of the glutathione detoxification system5. The glutathione that is oxidized during detoxification reactions is reconverted to active glutathione by enzymes requiring vitamin B2 (riboflavin) and vitamin B12. Thus, riboflavin

Gene Environment Interactions

Another way in which inherited susceptibility to cancer may be expressed is the way in which an individual can handle carcinogenic insults from the environment. For example, some individuals have a reduced capacity to metabolize carcinogens such as arylamines because of a slow acetylator phenotype, related to polymorphisms in the N-acetyltransferase-2 gene. Others may have a decreased ability to detoxify a number of carcinogenic agents due to polymorphisms in the glutathione S-transferase gene GSTM-1 or cytochrome P-450 genes CYP2A6 or CYP2D6. Genes that regulate metabolism of drugs and other xenobiotics are often discussed under the heading of pharmacogenetics. A number of genetic polymorphisms that are related to human pharmacogenetic disorders are listed in Table 3-11. Evidence from a study of monozyotic

Xenobiotic and Other Orphan Nuclear Receptors

Animal studies have shown that in addition to the phase II xenobiotic metabolizing enzymes, as described in Section VII.C, some carotenoids are capable of inducing CYP enzymes, constituents of the phase I detoxification pathway. Canthaxanthin and astaxanthin induced liver CYP1A1 and CYP1A2

Traditional Views Of The Cp

Lying within the central ventricular system, the CP is in an ideally suited position to monitor and modulate the functional status of the brain. The CP protects the brain against acute neurotoxic insults by using a complex, mul-tilayered detoxification system. First, the CP contains high concentrations of glutathione (GSH), cysteine, and metallothioneins that potently sequester toxic agents. Second, the CP uses protective enzymes, e.g., superoxide dismutase, GSH-S-transferase, and GSH peroxidase and reductase, to provide a barrier against free-radical oxidative stress. Third, the CP aids in the overall biodistribution of drugs and toxic compounds by using a full compliment of metabolizing enzymes, including phase I enzymes used for the functionalization of such drugs as cytochrome P-450 (CYP) isoform CYP2B1,2 and monoamine oxidase, phase II enzymes used for the conjugation of drugs (e.g., UDP-glucuronosyl transferase), and phase III activity, which provides kidney-like transport...

Conventional Drug Delivery 211 First Pass Effect

Drug Routes And First Pass Effects

The most popular route adapted for the intake of a drug is the peroral route better known as the oral route. The drug stays in the stomach for a considerable time during the process of digestion. Various body fluids such as gastric acids interact with the pill in the stomach. After digestion, the pill, along with other food particles that are broken down in the stomach, goes through the intestine where it is absorbed through the intestinal walls into the enterohepatic circulation where the pill, now broken down to its constituent drugs, is taken to the liver for detoxification. The process of the drug's encounter with the liver is referred to as the first pass effect 3 . After having undergone the first pass effect the drug completely mixes with the blood stream. Fig. 2.1 3 depicts, step by step, various barriers encountered by an orally delivered drug 2 . The first pass effect is of great significance to the pharmaceutical and health care industries because it greatly determines the...

Quantitative Sar Qsar analysis in the safety assessment of constituents

Relatively small differences in substructural features may have a dramatic effect on the metabolism of the constituent or the analog, or even alter the reactivity of the molecules with DNA (genotoxic versus nongenotoxic), thus changing the detoxification pathway or the molecule's mode of action. For example, metabolic activation of N-nitrosamines to potential carcinogenic metabolites is thought to proceed through hydroxylation at the carbon alpha to the nitroso group. Hydroxylation is followed by the release of the hydroxyalkyl moiety as an aldehyde and the generation of a primary nitrosamine (Klaassen, 2001). The primary amine ultimately forms a carbonium ion that can interact with DNA. Therefore, the use of nitrosamines containing aliphatic chains (see Fig. 7.1) may not be suitable analogs for N-nitrosodiphenylamine (see Fig. 7.2) since Fig. 7.2 does not contain a carbon alpha to the nitroso group that can undergo hydroxylation thus altering the metabolic detoxification pathway for...

High Efficiency Selection Of Stable Cell Lines Selectable Markers

Folate Metabolism Dhfr

Many of the dominant selectable markers are bacterial antibiotic resistant genes or genes that detoxify the effects of various protein synthesis inhibitors on the cell. For example puromycin N-acetyltransferase renders the cell resistant to the protein synthesis inhibitor puromycin. The dominant feature of these markers refers to the fact that there is no background activity of this sort expressed by the

Supragingival Irrigation

Subgingival Irrigation

Oral irrigation lias been shown to disrupt and detoxify subgingival plaque and can be useful in delivering antimicrobial agents into periodontal pockets.1 H Irrigation can be supragingival or subgingival. Daily supragingival irrigation with a dilute antiseptic, chlorhexidine, lor o months resulted in significant reductions in bleeding and gingivitis compared with water irrigation and chlorhexidine rinse controls. Irrigation with water alone also reduced gingivitis significantly but not as much as the dilute c hlorhexidine.SJ

Tests For Liver Function

The clinical laboratory offers several tests for the assessment of liver function. The enzymes alkaline phosphatase, ALT, AST, GGT, and 5'-nucleotidase are helpful in the assessment of the proper functioning and inflammatory status of the liver. Because the liver is the site for metabolism of carbohydrate, protein, and lipids, as well as for the synthesis of many proteins, the conjugation of bilirubin, and detoxification of drugs and other substances, the liver may be assessed by measurement of total and direct bilirubin, total protein and albumin, cholesterol and triglycerides, and urea and ammonia.1 Correlation of laboratory results across time is an indication of accuracy and appropriateness of results. In this case, increased levels of enzymes and bilirubin and lowered protein correlate with liver disease. The extent of the increased alkaline phosphatase and the presence of increases in both total and direct bilirubin help to specify this liver disorder as obstructive jaundice.2-5

Mechanisms of drug induced acute renal failure

When considering the mechanism by which drug causes nephrotoxicity, two components of renal function are decisive. The first are the renal transport processes which are critical to recovering essential minerals and nutrients from the glomerular filtrate and the second are the renal enzyme systems which are essential to both detoxification of xenobiotics and maintaining the body's acid base homeostasis 22, 23 .

Buprenorphine Subutex

Buprenorphine is an opioid with mixed agonist-antagonist properties that may be abused or used as an alternative to methadone in detoxification from opiates (21). It is taken sublingually, and self-administration of the drug in the custodial environment must be personally supervised by the doctor who should observe the patient for 5 min to ensure that the drug has fully dissolved (22). An unusual property of buprenorphine is that after chronic administration the onset of the abstinence syndrome is delayed. Heroin addicts who are dependent on a small dose of opiate can be transferred onto buprenorphine, which can be withdrawn fairly easily because of the delayed onset of the abstinence

Modulation By Carotenoids Of Cytochrome P450 Enzyme Activities In Animal Studies

This group (20) has also investigated the effects of carotenoids on mouse liver xenobiotic-metabolizing enzymes. An earlier study described above (4) reported a strong decrease in cytochrome P450 activity in mice fed b-carotene. Astorg and coworkers (20) compared the effects of b-carotene, the three carotenoids that they had previously reported to induce CYP1A in rat liver (canthaxanthin, astaxanthin, and b-apo-8'-carotenal), and the classical CYP1A inducer 3-MC in Swiss mice. In contrast to findings in rat liver, only canthaxanthin showed some significant inducing effect on mouse liver CYP1A-dependent activities with a much weaker intensity than 3-MC. Astaxanthin and b-apo-80-carotenal showed no inducing effects. These authors noted that the fact that carotenoids have different effects on cytochrome P450 induction in Wistar rats and Swiss mice is not due to a lack of responsivity of Swiss mice to CYP1A inducers, as 3-MC showed approximately the same potency as an inducer in the mice...

Metabolism of Alcohol

Once absorbed, alcohol is eliminated at a fairly constant rate, with 90 being metabolized in the liver and the remainder excreted unchanged in urine, breath, and sweat. The rate of elimination in moderate drinkers may vary between 10 and 20 mg 100 mL blood h, with a mean of 15 mg 100 mL blood h. Chronic alcoholics undergoing detoxification have elimination rates of 19 mg 100 mL blood h or even higher (17). This increased rate of alcohol burnoff is believed to be a consequence of increased activity of hepatic microsomal enzymes (P450IIE).

Federal Regulations For Prescribing A Scheduled Controlled Substance

However, one must keep good records to document that the clinician is treating a pain syndrome, not the disease of narcotic addiction (opioid maintenance or detoxification). If the clinician is going to administer or dispense directly (but not prescribe), a Schedule II narcotic drug to a narcotic-dependent person for detoxification or maintenance treatment, the clinician must have a separate registration with the DEA as a NTP (21 CFR 1306.07). DEA does not impose any limitations on a physician or authorized hospital staff to administer or dispense but not prescribe narcotic drugs in a hospital to maintain or detoxify a narcotic-dependent person as an incidental adjunct to medical or surgical treatment of conditions other than addiction (21 CFR 1306.07).

Micronutrients Alcohol

Alcohol can cause widespread cell damage and fat peroxidation in the liver.8 Supplements may help protect against oxidative damage. Vitamin C may help detoxify alcohol9 Deficiency is very common in heavy drinkers and can produce heart and neuromuscular problems The main enzymes that detoxify alcohol are dependent on zinc, thus zinc deficiency impairs abilityto breakdown alcohol, increasing potential

Soluble Proteinpattern Changes Induced by AZC Treatment

Surprisingly, some of the polypeptides were down-regulated following AZC treatment. The decrease in protein level observed may due to size effects of AZC not directly related to the demethylating activity of the drug. MS identified 15 down-regulated polypeptides corresponding to 13 proteins (Table 10.1). Down-regulated proteins belong to various pathways such as those involved with the biosynthesis of porphyrins, cholesterol metabolism (HMG-CoA synthetase) and cell detoxification (glutathione-S-transferase P). The various pathways affected by AZC treatment are shown in Figure 10.3. Up- and down-regulated proteins were taken together and placed in their respective pathways for obtaining much information

Applications in Substance Abuse Research

Using such techniques, investigations haven fallen broadly into two areas as relates to substance abuse, including both the acute effects of drug administration and the long-term consequences of addiction on neuronal activity (e.g., during states of drug abstinence and or treatment). Among the first to exploit such techniques for studies of human drug abusers, London and colleagues (London et al., 1990) examined the effects of intravenous cocaine (30 mg) on rCGM using 18F FDG and PET. Cocaine induced global reductions in brain metabolism that were inversely correlated with ventricular size. These investigators posited that reductions in brain metabolism may be one mechanism whereby drugs are reinforcing rewarding. In addition, Volkow and colleagues have attempted to understand the metabolic correlates of both acute (i.e.,

Internet Link Protein Kinase Classification

Cytochrome P-450 hydroxylate many compounds. These include the hydroxylations of steroid hormone synthesis and the hydroxylation of thousands of xenobiotics (foreign compounds), including drugs such as phenobarbital and environmental carcinogens such as benzpyrene, a constituent of the smoke from tobacco and backyard grills. Hydroxylation of foreign substances usually increases their solubility and is a step in their detoxification, or metabolism and excretion. In some cases, however, some of these reactions activate potentially carcinogenic substances to more reactive species. Aflatoxin B, for example, is converted to a more reactive species either by hydroxylation or epoxidation.

Atypical Multidrug Resistance

Detoxification by Glutathione Transferases Another form of drug resistance in tumor cells arises from the intracellular detoxification of anticancer agents by the glutathione S-transferases, a group of intracellular enzymes consisting of three different isoenzymes, u, rc, a 30-33 . Increased activities of one of the isoforms may be responsible for the development of chemoresistance towards cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), doxorubicin, and daunorubicin especially in ovarian and gastrointestinal tumors. Altered enzyme activity, e.g. of topoisome-rase I (hydrolysis of one DNA strand) and topoisomerase II (hydrolysis of both DNA strands) or mutant topoisomerases can also lead to multidrug resistance in several cell types, e.g. melanomas 1, 34 .

Alphaglucosidase inhibitor blocks hydrolysis of an

Which results can be used as legal evidence dehydroepiandrosterone - 19-carbon molecule found in small amounts as a precursor to some estrogens in women and as a precursor to male sex steroids in men delta check - comparison of concentration an analyte to values from previous specimens in the same patient a form of quality assurance densitometry - using colorimetry to determine the quantity of a dense region, such as in protein elec-trophoresis densitometry dermatitis - an inflammatory rash desensitization - lowering of responsiveness detoxification - removal of waste or toxins from a

Differentially Expressed Proteins in Drugresistant Cancer Cells

Summarizing the results, we show that the following groups of proteins are involved proteins involved in signal transduction, heat shock proteins and other chaperones, enzymes involved in metabolic pathways, calcium-binding proteins, and proteins involved in drug detoxification. In the investigated pH range, no plasma membrane transporters (e.g. ABC transporters) were found to be differentially expressed using the above-mentioned protein extraction procedure. Furthermore, only some of these proteins have been previously linked to chemoresistance and this may be an advantage of the proteomic approach in studying chemoresis-tance. Two groups of proteins turn out to be differentially expressed in all three types of cancer and are furthermore interesting from the functional point of view these are the molecular chaperones and the proteins involved in drug detoxification. The results for both groups will be summarized briefly in the following.

Bioartificial devices

The liver is a complex organ, often referred to as the body's chemical factory. Its many functions can be classified as secretion of bile metabolism of proteins, fats, and carbohydrates detoxification of drugs and metabolites and storage of vital substances such as iron and vitamins. Under certain clinical conditions the liver may regenerate itself in a short span of time, thereby making assist systems practical. However, substitution for the required metabolic support is not possible with present knowledge. The culturing of hepatic cells or the use of liver cells or tissue in membrane modules that permit extracorporeal perfusion but prevent direct blood to hepatic cell contact is being experimentally investigated. The membrane may provide a means for containing the cells ensure the transport of oxygen, carbon dioxide, nutrients, and cell products and provide a barrier against immunologic linteractions between the cells or tissue and the patient. Because of this latter concern,...

Toxic Optic Neuropathies Definition

Ethambutol and other antitubercular drugs, cytostatic agents, heavy metals, hexachlorophene, and methanol can all cause a toxic optic neuropathy (also see Chap. 17). The first priority is to identify the offending agent and then to block further exposure. Specific measures that follow are determined by the nature of the toxin. The most common syndrome of toxic damage to the optic nerve chiasm is that of tobacco-alcohol amblyopia. It is thought that the toxin in question is cyanide, which is present in trace quantities in tobacco smoke. Interventional therapy with oral multivitamins (e.g., vitamin B complex) and intramuscular injections of hydroxycobalamine (the decyanated form of vitamin B12) can reverse the visual loss in the early stages of the disease. These vitamins are thought to chelate trace levels of cyanide and detoxify the affected tissues. Some individuals may be more at risk than others are, based on the composition of their mitochondrial DNA and variations in the...

Metabolism Of Cyanide

Cyanide Thiocyonate Conversion

A minor (approximately 20 under non-toxic conditions) but toxicological metabolic pathway (that may increase during CN poisoning) for CN involves the disulfide cystine. 2-ICA, or its tautomer 2-aminothiazolidine-4-carboxylic acid (2-ACA), is a detoxification product of CN that is formed by what is thought to be a non-enzymatic reaction of CN with cystine.38 Cyanide reacts with cystine producing p-thiocyanoalanine, which spontaneously undergoes ring closure to form 2-ICA and its tautomer 2-ACA (Figure 10.3). These tautomers are in rapid chemical equilibrium and exist in equal concentration in solution. The formation of 2-ICA may increase with increased exposure to CN. One mechanism for this increase may be the decreased pH in the cells that favor the formation of 2-ICA compared with the maximal activity of the sulfurtransferases at a much higher pH.

Mrp2 Mrp3 Mrp4 Mrp5 Bcrp

2.3 Alterations in Drug Detoxification y-Glutamlycysteinylglycine, or reduced glu-tathione, is nucleophilic and conjugates with electrophilic atoms in three primary reactions (l)nucleophilic addition of glutathione to electrophiles (e.g., detoxifies epoxides), (2) reduces lipid and DNA hyperoxides (e.g., thymine hydroperoxide), and (3) readily directly reduces some free radicals (e.g., hydroxy and carbon). Glutathione is present at high concentrations in tissues (0.1 10 mM) but is present in highest concentration in the liver (5-10 mM). At these high concentrations, glutathione can undergo nonenzymatic conjugation with nucleophiles. Cancer cells are noted for decreased glutathione concentrations when compared with the somatic tissues from which they are derived. Decreased intracellular glutathione pools prevent detoxification of nucleophiles. However, this decreased intra-cellular concentration of glutathione in some cell types is caused by overexpressionof MRPs land, which use...

H pylori Functional Genomics

Information about H. pylori energy metabolism and biosynthetic pathways was also gained from the genome sequence, including identification of the membrane-embedded F0 and catalytic Fj components of ATP synthase, dehydrogenases, menaquinone, cytochromes, and a terminal oxidase for respiration-coupled oxidative phosphorylation. Fumarate reductase, which may play a role in anaerobic and or aerobic respiration, as well as superoxide dismutase, catalase, and two peroxidases, presumably to detoxify oxygen species, are also present. Nonetheless, the genetic basis of microaerophily remains incompletely understood. Genes encoding enzymes for nitrogen assimilation, the tricar-boxylic acid cycle, and nucleotide metabolism have also been identified, and a metabolic model has been constructed from genomic information that provides an in silico network of almost 400 H. pylori enzymatic and transport reactions (70). More recently, a global transposon mutagenesis approach has been used to identify...

Current Therapy For Nerve Agent Exposure

Candidate enzymes with bona fide catalytic activity against nerve agents include the human organophosphorus acid anhydride hydrolases (OPAH), such as paraox-onase (hu-Pon). Additionally, the ability to generate catalytic antibodies in response to appropriate transition state analogs suggests that nerve agent-specific antibodies that catalyze hydrolysis of their ligands could be effective bioscavengers.33,34 Finally, the ability to engineer site-specific amino acid mutations into naturally occurring scavenger enzymes can allow investigators to alter the binding and or catalytic activities of these enzymes. In general, the use of scavengers with catalytic activity would be advantageous because small amounts of enzyme, meaning lower concentrations in circulation, would be sufficient to detoxify both large amounts of nerve agent (as in an acute exposure) or lower amounts of agent associated with low-dose exposure Levels 1, 2, and 3.

Environmental Transformations and Toxicity

PAHs require metabolic activation to produce their mutagenic or carcinogenic effects. The primary mechanism of PAH biotransformation in higher organisms is by cytochrome P450-based monooxygenases leading to detoxification and excretion. However, attack by cytochrome P4501A1 can activate certain PAHs such as B a P to form a mutagenic diol epoxide capable of forming DNA adducts. The carcinogenesis of nitro-PAHs involves ring oxidation and nitro-reduction to form Af-hydroxyamino-PAH intermediates that can bind with DNA. The formation of hydroxy-PAH metabolites allows PAHs to be excreted by higher organisms. PAHs can bioconcentrate or bioaccumulate in aquatic invertebrates such as molluscs that do not posses the ability for their biotransformation while fish can effectively biotransform PAHs, preventing biomagnification up the food chain.23

Application Of Mri To Study Metabolic Disorders

Spectroscopy investigations are performed to study brain chemistry and ascertain from the individual 1H visible chemicals some of the following information with regard to disease NAA for its role in mitochondrial oxidative metabolism and as a putative marker for neuronal viability as well as its role in lipid synthesis (source of acetyl groups) creatine and phospho-creatine as creatine to phosphocreatine energy conversion mediated is by creatine kinase choline, a precursor for neu-rotransmitter acetylcholine and membrane phospholipids, phosphatidylcholine, and sphingomyelin myo-inositol, neuronal signaling of the phosphoinositide pathway, osmoregula-tion, cell nutrition, and detoxification lactate, which is a byproduct of anaerobic metabolism, elevated concentrations resulting from glycolytic metabolism as happens in brain ischemia and glutamate and glutamine, which are major excitatory and inhibitory neurotransmitters in the central nervous system (CNS refs. 6 and 7).

Anticarcinogenic Effects

An alcoholic extract from the leaves of O.sanctum at doses of 400 and 800 mg kg (p.o.) for 15 days significantly elevated the activity of cytochrome P-450, cytochrome b , aryl hydrocarbon hydroxylase and glutathione S-transferase in mice. The effect was dose-responsive. The above mentioned enzymes are important in the detoxification of carcinogens and mutagens. Glutathione S-transferase represents an important defense mechanism in protecting cells against oxygen-derived free radicals and also from cellular lethality after exposure to anticancer drugs or ionizing radiation. These findings suggest that Ocimum leaf extract has the potential to block or suppress the events associated with chemical carcinogenesis (Banerjee et al., 1996).

Why Do We Need to Detect Sulfur

Sulfur is assimilated and used by several organisms in different ways. As a characteristic part of enzymes and structure proteins, it plays an important part in, for example, biological redox systems, blood coagulation, and the natural detoxification of many organisms and is essential for their development. On the other hand, many organic sulfur compounds such as thiols, sulfides, and disulfides are a risk to human health and the environment.

Preventive Effect Of Shosaikoto On Free Radical Generation During Endotoxemia

The liver is one of the main target organs of endotoxin attack. Detoxification of endotoxin is considered to be mediated mainly by the RES, particularly Kupffer cells, in the liver (Cook et al., 1980 Sakaguchi et al., 1982). Ischemia causes functional and structural damage to tissues or organs by generation of active oxygen species. The modification induced in the apolar side residues of the membrane phosphoglycerides by active oxygen generation are considered to bring about structural alterations in the membrane. Therefore, biomembranes and subcellular organelles are the major sites of lipid peroxide damage. In previous studies (Sakaguchi et al., 1981a, 1981b), endotoxin injection was shown to result in lipid peroxide formation and membrane damage in experimental animals, causing decreased levels of scavengers or quenchers of free radicals. Therefore, we investigated whether or not Sho-saiko-to can defend mice from damage by free radicals generated in the ischemic state of tissues...

Organochlorine Compounds Polycyclic Aromatic Hydrocarbons and Breast Cancer

Was not a dose-dependent relationship between exposure and adduct formation, suggesting that there is a threshold effect. This latter point is interesting because there are known polymorphisms in the enzymes that activate and detoxify PAHs, thus a pharmacogenetic analysis could reveal who may be at higher risk.

Questions and Answers

In all stages of the disease, including at the onset, vitamins have a protective function. Vitamin C, for instance, is decisive in the detoxification of the pharmaceutical drugs in the liver, which could otherwise lead to liver damage and liver cancer. Numerous studies have established that several other vitamins and substances have the same importance in cancer prevention. These include various antioxidants, such as carotenoids, vitamin E, coenzyme Q10, among others. No. The vitamins, minerals, and amino acids that are not used up by the body cells are simply excreted. Remember that the human body has learned to deal with these natural substances for thousands of years. On the other hand, pharmaceutical products were developed in the test tubes of the pharmaceutical companies only this century. The human body treats them as foreign substances or cell toxins that have to be detoxified.

Therapeutic Uses Daunorubicin is

On i.v. administration the drug is rapidly distributed into tissues but does not enter the central nervous system. Rapid liver reduction to daunomyci-nol is seen followed by hydrolytic or reductive loss of the sugar along with the oxygen atom with which it is attached to the ring system. These two reactions also can take place before reduction. Demethylation of the 0-methyl ether moiety also occurs followed by sulfation or glucuronidation of the resulting phenolic OH. These and other transformation products have lesser bioactivity (186). Patients with decreased liver function should receive smaller doses because they are not able to detoxify the drug effectively. The half-life is about 8.5 h and about 25 of the active drug is found in the urine along with about 40 in the bile (187). Liposomally encased daunorubicin ci-

Carcinogens

Studied is a compound called benzopyrene. This molecule, when intact, is not dangerous, but when a cigarette is smoked the benzopyrene enters the blood and travels to the liver where it is inadvertently activated. An important function of our liver is to detoxify our blood by breaking down a wide variety of compounds, from alcohol to aspirin. A special set of liver enzymes, called mixed-function oxidases, breaks the alcohol down and either stores or eliminates the pieces. In the case of

Case Scenario

Liver function includes many vital metabolic functions that involve secretory and excretory processes such as detoxification, synthesis of proteins, and catabolism of carbohydrates. As mentioned earlier, several laboratory diagnostic tests can be used to assess liver function, including total and direct bilirubin, total protein and albumin, urea, and ammonia. The role of bilirubin and protein analysis to assess hepatic function has already been discussed.

Scaleup Factors

The first problem on moving from a small multiple-process unit to a large unit process is usually oxygen limitation. To overcome this and supply oxygen without the damaging effects of air bubbles from sparging and the high stirring speeds needed to effect efficient mass transfer, bioreactors have been developed that oxygenate through a membrane inside the bioreactor or by external medium loops through hollow-fibre oxygenators (see Chapter 4, section 4.6). A related factor is mixing, and low-shear modifications to impellers or the airlift reactor concept have been introduced (see Chapter 4, section 4.7). A problem for anchorage-dependent cells is the limitation on surface area during scale-up. A huge range of reactors have been developed (multiple plates, spirals, ceramic matrices, glass beads see Chapter 3, Figure 3.6.1) but the most successful has been the microcarrier (Griffiths, 1991a). By growing cells on a small bead, which can be cultured analogously to a suspension cell, the...

Rb In Cervical Cancr

Cancer Markers Numbers

Phenotyping assays have been used in a number of studies to investigate relationships between enzyme activity and cancer risk. For example, a lack of activity of GST M1 has been associated with increased risk of lung cancer in a number of studies reviewed in 42 . Deletion of this gene can also be determined using polymerase chain reaction (PCR) methods, simplifying the investigation of the role of this enzyme. Similarly, single-nucleotide polymorphisms in a number of the phase I and II enzymes responsible for the activation and detoxification of chemical carcinogens have been identified 43 . These polymorphisms are frequently associated with altered enzyme level or function. Thus, a major area of research has been the determination of the frequency of specific polymorphisms in individuals with or without various cancers. A number of studies have demonstrated elevated risk for cancer development among carriers of specific alleles. While the increase in risk is often...

Polymorphism

Modifying MM risks in different individuals. The human xenobiotic metabolizing system is responsible for completing the detoxification of procarcinogens. The system comprises two classes of enzymes phase 1 cytochrome P450 and phase 2 enzymes, including glutathione S-transferases (GST Ml and GST T1), paraoxonase 1 (PON1), and N-acetyltransferases (NAT) 1 and 2. Interindividual variability in the xeno-biotic enzyme system can predispose certain racial groups to the carcinogenic effects of certain chemicals. In a case-control study using peripheral blood or bone marrow biopsy specimens from 90 Caucasian individuals and a control group consisting of 205 healthy Caucasian volunteer bone marrow donors, there was a significant increase in incidences of the GST T1 null PON1 BB and NAT2 slow acetylation genotypes in MM cases compared with controls. Multivariate analysis revealed that GST T1 null was the most significant risk factor for MM. Interestingly the GST T1 enzyme has been identified as...

Intervention

For patients who are ready to make changes, ask whether they can make a commitment to a goal, what that goal is, and what they can use to help them achieve this goal. Tilings to consider include social support (e.g., church) or treatment options including free community support groups (e.g., 12-step meetings), psychotherapy, and medication management. Writing down the plan to which they agree and asking them to sign it is a final tool that can help solidify their commitment to making the change. It is important to assess the risk of withdrawal symptoms based on quantity and chronicity of alcohol use and make appropriate arrangements for supervised, medically assisted detoxification, when appropriate. In summary, it is important to clearly convey, in a nonjudgmental manner, the levels at which drinking is risky, concern about the impact of a patient's alcohol use. and to provide a recommendation to reduce drinking. For patients with a substance-induced mood or anxiety disorder,...

Actinomycetes

Twenty two ethanolic extracts of seaweeds collected from Karachi Coast, Pakistan, were screened for brine shrimp cytotoxic activity. Of these only six extracts showed significant activity.116 Sixty extracts of marine algae and invertebrates from Bulgarian Black Sea Coast were examined for inhibitory activity on the reproduction of influenza virus in tissue culture.117 The extracts of 10 ascidians collected from the northestern Brazilian Coast were tested for cytotoxicity using brine shrimp lethality assay, sea urchin egg development assay, hemolysis assay, and MTT assay using tumor cell lines and the extract of Eudistoma vannamei showed the highest toxicity in brine shrimp assay LD50 34.7 g ml).118 Robust microtiter plate based assay method for assessment of bioactivity was developed.119 The Pacific razor clam Siliqua patula was known to retain domoic acid, a water soluble glutamate receptor agonist produced by diatoms of the genus Pseudonitzschia. The mechanism by which razor clams...

Box 732

Nients are not suitable lor the preparation and detoxification of the implant surface. Mechanical instrumentation may damage the implant surlace il performed with metal instruments harder than titanium.1 Ihe method of choice involves the use of a high-pressure air powder abrasive (mixture of sodium bicarbonate and sterile water). This method removes microbial deposits completely front titanium surfaces, does not change Ihe surface topography significantly, and does not adversely affect cell adhesion.1,1' There have been some warnings for the potential of air-emphysema when using high pressure air spra instrumentation in the surgical site.1' ( linical case reports have shown successful treatment of periimplant disease with a protocol for detoxification using an air-powder abrasive.-''' Preparation of the implant surface has also been achieved by applying chemotherapeutic agents. Different agents,s v have been evaluated for this purpose, and it has been reported that the use of a super...

Diet Alcohol

Further lowers nutrient absorption from foods. The liver is particularly vulnerable to alcohol - more than three drinks a day causes inflammation and accumulation of fat in the liver. This impairs liver function, reducing the ability to detoxify chemicals and drugs. Because the liver is important for blood sugar control, alcohol-induced liver damage can produce hypoglycemia, leading to fatigue, irritability, and concentration difficulties. Alcohol increases urinary losses of many minerals, including zinc, calcium, and magnesium.5 Because of these effects, a diet rich in fresh fruits and vegetables, whole grains, lean meats, and low-fat milk products should be carefully chosen.

Mycobacterium leprae

Transcriptional regulators, transport proteins, polyketide synthesis systems, detoxification enzymes, and DNA repair processes are impaired. These defects likely account for the fastidious growth requirements ofM. leprae. Many putative virulence factors, such as the mce genes, PE PPE genes, and all PE-PRGS genes are also absent or defective. As in some strains of BCG, the mma3 gene, required for synthesis of methoxymyco-lates, is defective (70). Similar to M. avium subsp. paratuberculosis, the mycobactin siderophore biosynthesis (mbt) operon is nonfunctional, suggesting that iron metabolism is impaired. At the same time, M. leprae has an extra NRAMP-like metal transporter, which may compensate for the mbt defect. Other genes not found in M. tuberculosis, and possibly beneficial to intracellular survival of M. leprae, include a uridine phos-phorylase, a eukaryote-like adenylate cyclase, and a putative sugar transport system.

Modern Well Being

The universe, derived from both eastern Asian and Western classical-vitalist cosmologies. It pays close attention to the action of primary elements (earth, air, fire, water, metal, and wood), and to the old existential or environmental categories such as air, food and drink, exercise, sleep and work, the evacuations, and passions of the mind. The body is seen as existing in a biological envelope through which the cosmic physical forces of 'bio-energy' (or ying and yang) flow with a transcendent psychic energy that can be either harmful or benign. There is a particular interest in the tonic therapeutic actions and reactions of the five senses (acting not only through the nose, but through the eyes, the hands, the ears, and the voice) and in psychosomatic medicine generally the term favoured by progressive holistic GPs is 'biopsychosocial medicine'.46 The techniques used to control bio-energy are mainly those preserved and developed in the ancient practical-medicine traditions of...

Kidney Assist

The kidney's function is to maintain the chemical and water balance of the body by removing waste materials from the blood. The kidneys do this by sophisticated mechanisms of filtration and active and passive transport that take place within the nephron, the single major functioning unit in the kidney, of which there are about 1 million per kidney (Fig. 1). In the glomerulus, the blood entry portion of the nephron, a blood filtration process occurs in which solutes up to 60,000 Da are filtered. As this filtrate passes through the nephron's tubule system, its composition is adjusted to the exact chemical requirements of the individual's body to produce urine. In addition to these functions, the kidneys support various other physiological processes by performing secretory functions that aid red blood cell production, bone metabolism and blood-pressure control. Renal failure occurs when the kidneys are damaged to the extent that they can no longer function to detoxify the body. The...

Ayurveda

There are four steps to ayurvedic therapy detoxification, palliation, rejuvenation, and spiritual healing. Bowel purges, phlebotomy, enemas, and nasal douches are all utilized to purge impurities from each of the doshas. Diet, medications, herbs, and yoga are used to bring the now-cleansed doshas back into alignment. Once balanced, the body's functions are strengthened and rejuvenated with additional herbal and exercise

Mefloquine

The mechanism of action of quinoline-con-taining compounds has been the focus of much research. Despite extensive scrutiny, the exact mode of action of mefloquine is not known. Its effects are confined to the pathogenic blood stages of the parasite. Most recent studies support the proposal that mefloquine interferes with the parasite's ability to detoxify heme. Based on ultra-structural changes observed in vitro, the parasite food vacuole is the primary target of mefloquine action and the affinity of mefloquine for free heme is high. Like chloro-quine, mefloquine has been demonstrated to inhibit heme sequestration. For a more complete discussion, see Section 2.3.