Detoxification and Cleansing Programs

Soursop Tea Detox

The creator of this program is Kimberly French, a professional pharmaceutical scientist. Her secret that led to the creation of this program was discovered on her visit to the Brazil rainforest. The author has also been a victim of overweight and has had the experiences that come with the condition, including low metabolism, tiring easily, frequent hunger and craving for food and also frequent mood swings. Understanding the situation faced by those like her, she created this program to help them work their way out of overweight as she did. This guide contains a comprehensive solution to weight loss and detoxification of your body. You will know how to get rid of toxins like nitrates, pesticides and GMOs. The effectiveness of this program has been proven over the years by the testimonies associated with it. This program has assisted many individuals to get rid of unwanted fats in their body and become stronger and healthier. From this program, you will get to increase the metabolism of your body, suppress your appetite and cravings for food, boost your energy levels, and finally improve the immune system of your body. There are also other bonuses attached to purchase of this program and they include; Fat Killing Exercise, Fat Torching Foods and Recipes, and 40 Thoughts That Sabotage Your Weight Loss Read more...

Soursop Tea Detox Summary

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Oxygen detoxification

E. histolytica lacks catalase and glutathione-dependent enzymes normally associate with oxygen-related detoxification (Fahey et al. 1984). It contains a single copy of an iron-containing superoxide dismutase (Tannich et al. 1991) to remove superoxide ion and several peroxiredoxins capable of removing both hydrogen peroxide and organic peroxides, including phospholipid hydroperoxides that would otherwise damage the cell membranes. Peroxiredoxins depend on thioredox-in and thioredoxin reductase and candidate genes for both of these have been found. Other proteins that may protect the organism from intracellular peroxide have also been identified, including genes encoding rubrerythrin and flavoprotein A, which may detoxify nitric oxide (Bruchhaus I, unpublished analyses). The redundancy of anti-oxidant pathways underscores the sensitivity of this amitochondrial organism to the presence of oxygen. Experimental evidence suggests that only low levels of oxygen can be tolerated and in the...

The Molecular Pathogenesis of Human Prostate Cancer

Recent studies of the earliest molecular steps in the development of human PCA have generated new evidence supporting causative roles for prostate inflammation and diet in prostatic carcinogenesis. These new findings have provided new clues as to how PCAs likely arise, and new insights into how the disease might be prevented. A new lesion, termed proliferative inflammatory atrophy (PIA), in which prostate epithelial cells undergo regenerative proliferation in response to inflammatory damage, appears to be a precursor to prostatic intraepithelial neoplasia (PIN) and to PCA (7). PIA lesion cells exhibit many signs of stress, including the induction of carcinogen-detoxification enzymes such as glutathione S-transferases GSTA1 and GSTP1 (7). Somatic inactivation of GSTP1, encoding the human GST, renders prostate epithelial cells vulnerable to

Human Coppertransporting Atpases As Members Of The Ptype Atpase Family

In addition to their important role in delivering copper to the copper-dependent enzymes, human copper-transporting ATPases regulate the intracellular concentration of copper by removing excess copper from the cell. This detoxification function of copper-transporting ATPases is very similar to the functional role of bacterial Cd2+-ATPase and Pb2+-ATPases and likely appeared first during evolution. It was later extended to accommodate eucaryotic cell needs in having copper inside various cell organelles. To carry out this dual function, WNDP and MNKP have to be located, at least temporarily, in different cell compartments.

New Opportunities for PCA Prevention

The convergence of PCA epidemiology, indicating a possible role for prostate inflammation, and a significant role for the diet, in PCA development, with molecular pathology, revealing that neoplastic prostate cells may have acquired an increased vulnerability to carcinogen damage, provides an opportunity for the discovery and development of rational new approaches to PCA prevention. Possible strategies include reduced exposure to genome damaging oxidants and other carcinogens, and intake of antioxidant micronutrients, including vitamin E, selenium, and carotenoids such as lycopene, which may be able to intercept reactive oxygen species before they inflict genome damage in the prostate. Administration of anti-inflammatory agents, when distributed into prostate tissues, may reduce oxidant production by prostate inflammatory cells. Consumption of cruciferous vegetables, containing the isothiocyanate compound, sulforaphane, an inducer of GSTs and other carcinogen-detoxification enzymes,...

Genetic Engineering Strategies to Enhance Host Resistance to Mycotoxin Contamination

Genetic engineering may provide innovative solutions to prevent the accumulation of fumonisins in Fusarium-infected maize. One approach currently under development is detoxification of fumonisins by enzymes introduced into maize via genetic engineering. Enzymes that detoxify and degrade fumonisins have been identified from Exophiala spinifera, a black yeast found on moldy maize kernels. The initial steps in fumonisin detoxification are ester hydrolysis followed by oxidative deamination to produce derivatives that lack the free amino function that is believed to be important for toxicity (Blackwell et al. 1999). Genes encoding the deesterification and deamination enzymes have been cloned

Oxylipin Biosynthesis

The fatty acid hydroperoxides generated by the activity of LOX are potentially deleterious to membrane function by causing increased rigidity and would not, therefore, be expected to accumulate (123). Hydroperoxides can be metabolized by several routes. Glutathione transferases (GSTs) exhibiting glu-tathione peroxidase activity toward phospholipid hydroperoxides have recently been demonstrated in mammalian tissues (124). GSTs in plants perhaps having analogous roles in hydroperoxide detoxification could be envisaged (125). Hydroperoxide fatty acids can also be metabolized by the peroxygenase cascade (126-128). This involves (a) an intramolecular transfer of one oxygen atom from fatty acid hydroperoxide yielding an epoxyalcohol and or co-oxidation reactions such as epoxidation of double bonds of unsatu-rated fatty acids, and (b) an epoxide hydrolase, which preferentially hydrates the epoxides formed by the per-oxygenase (127). The chloroplast envelope membranes appear to be a major...

Segmental Duplications And Evolution

Finally, a recent survey of segmental duplications in the human genome found that approx 6 of transcribed exons are located in recently duplicated sequence (2). Genes associated with immunity and defense, membrane surface interactions, drug detoxification, and growth and development were preferentially enriched, suggesting that gene duplication plays a major role in the evolution of these functions. Thus, in contrast to the popular conception in which single nucleotide polymorphisms and small mutations are the major method of evolutionary change, larger genomic rearrangements may instead represent the driving force behind much of recent primate evolution, facilitated by the presence of abundant highly homologous duplicated sequences throughout the genome (68).

Application Of Computational Methods To Copper Proteins

In a recent work, a model for the incorporation of metal from the copper chaperone CCS into Cu,Zn SOD has been proposed (32). Previous studies have identified the human copper chaperone CCS as the presumed factor responsible for copper incorporation into SOD (34,35). The 3D structure of CCS was homology modeled using the periplasmic protein from the bacterial mercury-detoxification system (36) and the structure of one subunit of the human SOD dimeric enzyme (37) as templates. On the basis of the 3D model, a mechanism for the transfer of copper from CCS to SOD is proposed that accounts for electrostatic acceptor recognition, copper storage, and copper-transfer properties. The proposed model identifies a path for copper transfer based on the presence of differ

Innate Immune Recognition of Commensals in Symbiosis in Other Organisms

Recent investigations in squid and zebra fish indicate that signaling via TLRs (or other pattern recognition receptors) may be involved in mediating host-microbe mutualism in animals other than mammals. Studies in the symbiosis between the bacteria Vibrio fisheri and the Hawaiian sepiolid squid, Euprymna scolopes have revealed that LPS, peptidoglycan, and tracheal cytotoxin may be responsible for various aspects of light organ development (Foster et al. 2000 Koropatnick et al. 2004 Nyholm et al. 2002). The microbial flora of the zebra fish digestive tract was found to induce a widespread host gene expression program (Rawls et al. 2004). Fifty-nine of the 212 genes upregulated on microbial colonization of zebra fish were shared with those induced on introduction of commensals to mice, revealing an evolutionarily conserved response to the intestinal microflora. These include genes involved in many biological processes such as epithelial proliferation, nutrient metabolism, and innate...

NO Dioxygenation by HbO2

It has been known for a long time that the addition of NO to either HbO2 or oxymyoglobin causes a very rapid and stoichiometric oxidation of the heme group and formation of nitrate (see references in refs. 47 and 48). This reaction has been used for more than 20 yr as a simple assay for NO synthase activity (for a review, see ref. 49). However, the physiological importance of this process has become clear only within the last 10 yr. HbO2 in red cells and oxy-myoglobin in muscle tissue detoxify NO by converting it to NO3-. This scavenging function prevents NO from being transported into actively respiring tissue, where it would inhibit both aconitase and cytocrome oxidase and shut down oxidative phosphorylation (50-53). Gardner (54-56) has called this activity NO dioxygenation and has shown that it is catalyzed efficiently by flavohemoglobins from various microorganisms, in which the expression of the gene is turned on by the addition of toxic levels of NO. Extracellular Hb scavenges...

Feeding ecology and diet

In all species, the predominant diet is shoots and leaves of forest trees. Sloths feed on Cecropia, the most abundant tree of the Amazonia forest. Regenerating agricultural land river margins and natural gaps may sometimes be important (despite the biting ants that swarm in the tree's hollow stems), but it is never the sole food source. The idea that Bradypus sloths feed only on Cecropia probably arises because an open growth form makes a sloth in a Cecropia easier to see than in almost any other kind of rainforest tree. When feeding, the forelimbs are used to pull leaves slowly towards the mouth. Sloths are highly specialized for an existence that centers around squeezing as much energy as possible out of a low-intake rate of highly indigestible food. This is because leaves eaten by Bradypus sloths are, though energy-rich, also rich in tannins and fiber. Digestion must therefore be a simultaneous process of detoxification and energy extraction. The gut is extensive, making up 30 of...

Examples Of Metabolic Determinations

Similarly, Phormia can be used to study the age-dependent capability of xenobiotics via the GSH-S-transferase (GST) system for detoxification (Collatz and Flury, 1992). Using the analgetic drug Paracetamol, we were able to show that both a reduced GSH level and a diminished activity of GST lead to an increasing mortality of old flies after drug injection.

Ethical Issues in the Quality of Care

Evant systems such as criminal justice, social rehabilitation, education, and or employment. If such demedicalization occurred, outcome measurements for health would be established that specifically addressed only those activities and results for which the system could reasonably be responsible. For example, safe detoxification and or supervised withdrawal for the chemically dependent could be one valid outcome measure.

General Considerations In Assay Performance

The MTD doses used in these studies often tend to be several orders of magnitude higher than the expected human exposure levels. It has been argued that such doses are irrelevant for safety assessment and risk evaluation because they may overwhelm or saturate the body's defense and protective mechanisms, such as the detoxification pathways, DNA repair mechanisms, and others. In certain cases, administration of unusually high doses may lead to the saturation of primary detoxification pathways, which in turn may lead to the formation of unusual metabolites through alternate metabolic pathways a situation unlikely to be encountered during normal human exposure The target tissues available for analyzing genotoxicity depend on the objective of the study and the type of assay used. Bone marrow and liver are the two most commonly used tissues for these analyses. Bone marrow, by virtue of its high mi-totic rates, has been a favorite for cytogenetic analysis. Another feature that makes...

Cellular Copper Homeostasis

Evolved to handle copper is the dual nature of copper in biological systems Copper is both an essential cofactor for various Cu-dependent enzymes and a potential pro-oxidant. To function normally and to protect itself from potential damage a cell must be able to sense and respond to changes in intracellular copper levels. Different mechanisms will be activated in response to deficiency or excess as cells adopt an acquisition or detoxification mode depending on their copper status. Whole-body copper homeostasis depends on these mechanisms, which are modified in cells such as the intestinal enterocyte (acquisition) or the hepatocyte (detoxification). These modifications are discussed in more detail in Section 2.3. (see Figs. 3 and 4).

Importance To Quality Of Food

The importance of laccase to the quality of food is directly related to its proposed biological function. Laccases are found in a variety of plants, fungi, and even some bacteria. In higher plants, laccases are thought to be involved in lignification and detoxification protection. In fungi, laccases produce colored pig

Liudvikas Jagminas md facep

Decontamination is defined as the reduction or removal of chemical, biological, or nuclear agents so they are no longer hazards. Agents may be removed by physical means or be neutralized chemically (detoxification). Decontamination of the skin is the primary concern, but decontamination of other systems must also be done when necessary. To ensure appropriate and timely patient care as well as optimal response, emergency personnel must understand decontamination procedures and the proper use of personal protective equipment.

Importance of Identifying Transcriptional Regulatory Networks in Toxicogenomics

The liver is the first organ that encounters toxins that have been absorbed through the intestines. One of the major roles of the liver is detoxification and metabolism of xenobiotics 7 . Particularly with regard to predicting the toxic action of xenobiotic compounds, identification of all targets of liver-specific TFs (for review see Schrem et al. 8, 9 ) would constitute great progress in toxicogenomics. Substances could be grouped mechanistically by targeting the same TF pattern, and prediction of toxic action would then be possible through analyses of changes in TF binding prior to observable damage to the tissue.

Model Body Size And Scaling

However, metabolism or detoxification and excretion of a drug are not directly correlated with body size but, more accurately, to metabolic rate of the animal (see Schmidt-Nielsen29 30 for more details). Kleiber31 in 1932 was the first to demonstrate that in a log-log plot of mammalian body weight to metabolism, the graph forms a straight line with a slope of 0.75.

Uses And Interpretation Of Data

The in vitro micronucleus assay provides an easy method for assessing the influence of different genotypes on induction of genotoxicity. These studies involve genetically engineered cell lines, as well as human and rodent genetic variants. To investigate the effect of metabolism on genotoxicity of nitroarenes and aromatic amines, sublines of Chinese hamster cells stably expressing human NAT1 or NAT2 N-acetyltransferases or Salmonella typhimurium O-acetyltrans-ferase were compared for sensitivity to micronucleus induction (78). Cells expressing human NAT2 N-acetyltransferase had the highest sensitivity to chromosome damage induced by nitroarenes. Norppa (79) discussed how the in vitro micronucleus assay (among other cytogenetic methods) can be used to study the effect of human polymorphisms, such as in the detoxification enzyme glutathione S-transferase.

Solidstate bioprocessing

Resulted due to the hydrolysis of ellagotannins by tannin hydrolyzing enzymes produced by the fungus. Further, it is suspected that phenolic enrichment could also occur through contribution from the growing fungal species. The endogenous phenolics present in the fruit wastes could be toxic to the growing fungus. In an attempt to adapt and utilize the substrate for growth, the fungus could be detoxifying the phenolics biochemically using a variety of enzymatic systems present in the fungus. The fungal detoxification can occur by a variety of mechanisms including methylating or demethylating the pheniolic ring, or by hydroxylation (219,220). Recent studies have shown methylated phenolic phytochemicals have excellent antibacterial properties against Gram-positive bacteria (221). Hydroxylation of the phenolic ring by the fungal system during its growth increases antioxidant properties (19) and therefore, phenolics resulting from biotransformation occurring during the solid-state...

Stevensjohnson syndrome

The exact mechanism producing SJS and TEN is unclear. Patients with SJS and TEN induced by anticonvulsants or sulfonamides may have an alteration in the detoxification of reactive drug metabolites. CD8 cells predominate in the lesions of blistering reactions, suggesting a cell-mediated cytotoxic reaction against epidermal cells (32). Tumor necrosis factor-a, perforin, granzyme B (GrB), and Fas Ligand (FasL) have been shown to be increased in the early stage of disease, further supporting a cytotoxic mechanism (33).

CO poisoning and pulmonary oedema

For these patients, pulmonary oedema was an indication for HBO, since HBO accelerates myoglobin detoxification. - non-cardiac related The 2nd group included 28 younger patients (aged 18 + 11 years), usually without previous heart pathology. The mechanism of pulmonary oedema was non-cardiogenic -either by toxic effect of the CO, or aspiration of gastric content (in 20 out of 28 patients). In these cases, the risk-benefit decision regarding HBO was made on the basis of reducing neurological risk in exchange for possibly increasing the pulmonary problems.

Genetic control of leaf senescence and fruit ripening

Phloem during senescence and are regarded as the main transportable amino acids (Buchanan-Wollaston and Ainsworth, 1997). ATP sulphurylase is involved in the biosynthesis of cysteine and methionine. It has been proposed that during senescence the up-regulation of ATP sulphurylase leads to a subsequent increase in the cysteine pool. Cysteine is the precursor for glutathione biosynthesis, a major antioxidant, which, in addition to its role in the recovery of ascorbate and scavenging of reactive oxygen species (ROS), also acts in the transport and storage of sulphur (Rennenberg, 1982), the regulation of cell division and development (Earnshaw and Johnson, 1985), the regulation of gene expression and signalling (Wingate et al., 1988 Herouart et al., 1993 Moran et al, 2001) and the detoxification of xenobiotics and heavy metals (Delhaize et al., 1989 Halliwell and Gutteridge, 1986 Timmerman, 1989).

Crossspecies Gene Protein Comparative Expression Profiling

Cial for the interpretation of cross-genome expression profiles in an integrated health and ecological risk assessment. A core set of homologous genes should include genes involved in xenobiotic activation detoxification mechanisms, perturbations of cell homeostasis mechanisms, oxidative damage, cell injury, death, and regeneration and genes controlling critical signalling mediator molecules for these biological processes. Phase I and Phase II enzymes metabolize most environmental xenobiotic chemicals, and much is known about their chemical substrates, inducers, and inhibitors. Phase I enzymes, the cytochromes P450 (CYPs), both bioactivate and also detoxify xenobiotics. The primary step involved in the activation process mediated by CYP proteins is oxidation, or bioactivation of xenobiotics to electrophiles. Phase II enzymes conjugate some of these oxidized metabolites to form water-soluble excreta-ble substances. We propose to begin our compilation of cross-species gene protein...

Overview Of Biomarkers

Biomarkers of susceptibility are mainly concerned with factors in kinetics and dynamics of uptake and metabolism of exogenous chemicals. The enzymes involved in activation and detoxification of these xenobiotics are divided into two categories phase I enzymes, mainly the superfamily of cytochrome P450 mixed function oxidase enzymes, and phase II enzymes, which act on an oxidized substrate to conjugate them with various moieties, such as glucuronic acid, glutathione, and sulfate (62-64). Genetic differences in the expression of these metabolic enzymes could be a major source of interindividual variation in susceptibility to disease (65-67). Therefore, the determination of genotype and phe-notype of these metabolic enzymes in different populations is being studied to determine if an association exists between exogenous exposure and formation of specific disease in specific metabolic genotype subsets. Many studies over the past several years have found that genes involved in xenobiotic...

Application Of Biomarkers For Human Risk Assessment

McGlynn et al (153) have reported that mutant alleles at two AFBj detoxification gene loci (epoxide hydrolase EPHX and GSTM1) were significantly overrepresented in individuals with detectable serum AFB1-albumin adducts in a cross-sectional study. Mutant alleles of EPHX were also significantly overrepre-sented in persons with HCC in a case-control study. The relationship of EPHX to HCC varied with HBsAg status and suggested that a synergistic effect may exist. Mutations of p53 at codon 249 were only observed among HCC patients with one or both mutated EPHX and GSTM1 genotypes. These results indicate that individuals with mutant genotypes at EPHX and GSTM1 may be at greater risk of developing AFB1 adducts, p53 mutations, and HCC when exposed to AFB1. Hepatitis B surface antigen carriers with these high-risk genotypes may be an even greater risk than carriers with low-risk genotypes. These findings further support the existence of genetic susceptibility in humans to AFB1 exposure and...

Quantitative Copperion Homeostasis

Organisms such as yeast have a remarkable ability to adapt to drastically varying copper-ion conditions. Yeast gene expression differs greatly under different copper-ion conditions (30), which implies that yeast can detect the changes in copper-ion concentrations. The transcription factor Mac1p plays a pivotal role in yeast copper-ion homeostasis. Mac1p controls copper-ion uptake by regulating the expression of genes encoding high-affinity copper-ion transporters CTR1 and CTR3 (29,31-38). Mac1p has also been shown to participate directly in copper-ion detoxification through a mechanism independent of CTR1 and CTR3 (39). We have also found that Mac1p might regulate the degradation of Ctr1p in response to toxic copper levels, by a yet to be explored mechanism independent of its regulatory role in CTR1 transcription (Zhu, unpublished results 40). A long-standing question in understanding how Mac1p senses copper ions and regulates CTR1 and CTR3 transcription was whether copper ions affect...

Mammalian Copperiron Link

In mammals at a whole-body level, copper absorption from the small intestine is, to some extent, regulated, with increased uptake when the animal is copper deficient and decreased uptake when the diet is adequate in copper (82). Details of the molecular mechanisms regulating absorption remain to be elucidated. The control of copper excretion, which is also an important part of the protection against excess copper exposure, is regulated by the liver, with excess copper being disposed of through the bile (83). Within the cell, excess copper is detoxified by at least two mechanisms sequestration by metal-binding proteins such as metallothioneins (MT) and enhanced export by the copper ATPases, MNK, and WND (84). Although a definitive biological role for MTs remains elusive despite years of research, MTs are known to be small cysteine-rich proteins that bind heavy metals, including copper, zinc, and cadmium, through cysteine thiolates (85,86). There are 17 genes encoding four isoforms of...

Regenerative Hyperplasia

Vestigators postulated that the difference observed between the gavage and drinking water studies can be explained solely by toxicokinetics. When given as a single bolus dose by gavage, the treatment resulted in a high rate of production of toxic metabolites in the liver that overwhelmed cellular detoxification mechanisms and killed the hepatocytes. When given in drinking water, ingestion was in small sips throughout the day. The chemical was probably not cytotoxic or carcinogenic under these conditions, as delivery to the target tissue was at rates low enough to allow detoxification, even though the cumulative dose was 329 mg kg day. The authors concluded that a model that assumes that tumor formation is secondary to proliferative effects describes the pattern of tumors more accurately than the linearized multistage model. They derived an NOAEL of 1800 ppm for induced cell proliferation and mouse liver tumors. Using a UF of 1000, a level of 0.18 ppm was considered a level below which...

Copperiron Link In Photosynthetic Organisms

Besides having the same copper and iron requirements as human and yeast cells, photosynthetic organisms have additional requirements for these metals in the plastid, where they are utilized as the redox active cofactors in many metabolic processes, including, in particular, the proteins involved in photosynthetic electron transfer in the chloroplast. Iron-containing cytochromes, Fe-S centers ( 20 atoms per PSII PSI unit), and copper-requiring plastocyanin are abundant proteins in photosynthetic organisms. Metal metabolism in this context presumably requires a completely separate set of factors in addition to those required for cellular and mitochondrial iron and copper metabolism. A further challenge for photosynthetic organisms is that biologically useful levels of soil copper and iron are low. The variability in the mineral composition of soils means that for plants to survive and grow they must adapt to the variation in supply of copper and iron. As with yeast and humans, the...

Significance to humans

The rediscovery of squid giant axons by J. Z. Young in the 1930s allowed experiments that demonstrated much of what is known about the basic functioning of nerves. The giant axons of squid nerves have been widely used as one of the primary bases of neurobiology. Cephalopods are also being used increasingly as models in other biomedical fields, including sensory biology, information processing, and biochemistry. They are even being used as a source of information regarding the detoxification of nerve gas. The results of an electronic search of scientific literature for the word squid may be dominated by biomedical studies based on inshore squid as a convenient and interesting model.

The Significance of Substance Abuse

There is growing evidence that patients with severe poly-substance abuse problems fare the worse with respect to neurocognitive outcome. Our analysis of the Brown CFAR cohort has revealed that patients with active IDU (primarily heroin addiction) had weaker cognitive function than patients without substance abuse history. This finding is consistent with results from studies comparing HIV patients who are gay vs. injection drug users, with the IDU showing greater cognitive impairment prior to being symptomatic with AIDS (281, 282). In contrast, patients with former IDU involving a single drug did not differ greatly from those without IDU after controlling for age, education, and level of depression in our CFAR cohort. This observation is consistent with results from other studies that have found limited cognitive impairment among heroin addicts after detoxification (283-285).

Glutathione Reduced GSH and oxidized GSSG

Glutathione (GSH, -glutamylcysteinylglycine) and its oxidized form (GSSG) (Figure 10. 7) together form the first line of defense against the cellular protection against reactive oxygen species (22,23,106,107). They carry out their protective functions by reducing ROS via their thiol groups, and therefore are involved in a variety of processes in the cellular systems that involve generation of free radicals such as detoxification of xenobiotics, reduction of hydroperoxides, and synthesis of leukotrienes and prostaglandins (106,107). The reducing power

GlutathionesTransferases

The glutathione-S-transferases (GST) are important phase II detoxification enzymes found mainly in the cytosol, and are involved in the detoxification of drugs and harmful chemicals in the body (112). They are found in very high concentrations in the liver, where they conjugate glutathione to the electrophilic centers of lipophilic compounds and increase their solubility in order to facilitate their excretion (113,114) (Figure 10.7). GST posses a wide range of substrate specificities and can catalyze the reduction of breakdown products of macromolecules formed as a result of oxidative stress including reactive unsaturated carbonyls, oxidized DNA bases, and hydroperoxides, and therefore play a vital role in protecting tissues against oxidative damage and oxidative stress (112-115). As a result of the beneficial functions of GST it serves as an important biomarker for oxidative stress (115). Most of the methods to assay the GST activity involve measuring the conjugation of...

Plant Cell Homeostatic Copper Networks

Although direct copper binding to metallothioneins has not been demonstrated in plants yet, there are at least two copper-regulated MT gene families in Arabidopsis (Fig. 1) whose function as copper chelators is mainly accepted based on functional complementation of the yeast mutant Acupl (20). The pattern of MT expression differs depending on the member of the family, but they accumulate in leaf trichomes, suggesting a detoxification mechanism similar to the secretory strategy used by halo-phyte plants that extrude salts (23). To date, no cis metalloregulatory elements, such as the metal-responsive element (MRE) sequences from yeast, nor other regulatory elements, have been found in the promoters of these genes (21). On the other hand, Arabidopsis plants transformed with a chimeric construct, based on a reporter gene under the control of the yeast metallothionein CUP1 promoter, do not respond to copper exposure (24). This result suggests that plants possess a copper-sensor regulatory...

The Role of HNFs in CYP Monooxygenase Expression

The foetal liver, the major site of haematopoiesis during embryonic development, acquires additional detoxification functions near birth. The response to xenobiotic exposure with expression of several cytochromes P450 (CYP) monooxygenases and drug efflux transporters is a vital hepatic function. Expression of the genes for these proteins is regulated by nuclear receptors such as the pregnane X receptor (PXR). The expression of several xenobiotic response genes as well as of HNF-4alpha is increased in foetal hepatocytes stimulated by the hepatic maturation factors oncostatin M (OSM) and matrigel. To determine the contribution of HNF-4alpha to xenobiotic responses in the foetal liver, foetal hepatocytes containing floxed HNF-4alpha alleles were cultured, and the HNF-4alpha gene was inactivated by infection with an adenovirus containing the Cre gene. As a consequence, expression of CYP3A11 and PXR was suppressed by inac-tivation of HNF-4alpha. An HNF-4alpha binding site was characterized...

Saprotrophs of Attached and Fallen Wood and Litter

Senescent leaves together with resident mycoflora will eventually fall to the litter or soil surface. Some phylloplane fungi (Aurobasidium spp. and Cladosporium spp.) may persist, and some may even complete their (sexual) life cycle during this phase. However their consequential net decomposition may be very low. Litter is rapidly colonized by certain soil-inhabiting fungi (e.g., Penicillium, Trichoderma, and Fusarium spp.), which appear to cause little direct litter decomposition, but may produce significant indirect effects, such as synergistically increasing decay rates with litter-agarics. The early ruderal strategists are progressively replaced by saprotrophic communities, which decay leaf surface waxes, pectins, and the lignocellulose complex itself. Later significant decay stages are associated with the litter-basidiomycetes, especially agarics such as Mycena, Marasmius, and Clitocybe, which form a significant portion of fungal biomass within litter. Such species are capable of...

Morphological Changes Accompanying Aging In S Ratti

Accumulation of age-pigment (lipofuscin) seen during mammalian aging. There is a similar increase in autofluorescence with age in free-living S. ratti morphs (Gardner et al., 2004). By contrast, little such autofluorescence was seen in parasitic females, even in 11-month-old individuals (Gardner, Gems and Viney, submitted). Lipofuscin accumulation reflects organismal failure to detoxify and excrete molecular waste products. The paucity of autofluorescence in S. ratti parasitic females suggests reduced generation, and or increased excretion, of damaged molecular constituents. This is consistent with aging occurring in the two S. ratti female morphs, but at very different rates. The parasitic and free-living females morphs of S. ratti are genetically identical. Therefore differences between these morphs must be due to differences in gene expression. This being so, these differences in intestinal pathology might reflect differences in regulated biochemical processes which determine...

Model Plant Species For The Genomicsbased Studies

Been carried out using microarray and macroarray based methods by several groups (Table 1). Two types of arrays have been made available for genomic studies in rice, namely oligonucleotides array as well as cDNA array. There are numerous examples wherein detailed studies have been taken in rice using these approaches. Analysis of salt stress-inducible ESTs from salt tolerant rice cultivar Dee-geo-woo-gen revealed several proteins showing homology to proteins functional for detoxification, stress response and signal transduction in plants (Shiozaki et al. 2005). Comparative analysis between different rice genotypes has also been attempted employing salinity tolerant (CSR27 and Pokkali) and sensitive (PB1) cultivars of rice (Sahi et al. 2003). This study highlighted that genes such as SalT, glycine rich RNA binding proteins, ADP ribosylation factor, NADP dependent malic enzyme, Mub ubiquitin fusion protein, tumor suppressor genes, wound inducible genes, ethylene response element binding...

Biological Function Of Phenolic Phytochemicals

Emerging research into the biological functionality of phenolic phytochemicals also strongly suggests their ability to modulate cellular physiology both at the biochemical physiological and at molecular level. Structural similarities of phenolic phytochemicals with several key biological effectors and signal molecules have been suggested to be involved in induction and repression of gene expression or activation and deactivation of proteins, enzymes, and transcription factors of key metabolic pathways (27,33-35). They are believed to be able to critically modulate cellular homeostasis as a result of their phys-iochemical properties such as size, molecular weight, partial hydrophobicity, and ability to modulate acidity at biological pH through enzyme (dehydrogenases) coupled reactions. As a consequence of many modes of action of phenolic phytochemicals they have been shown to have several different functions. Potential anticarcinogenic and antimutagenic properties of phenolic...

Extracellular Precipitation of Metals

Exceeding a solubility product leads to precipitation of an insoluble salt of the reacting species. Sulfide anion (S22) and oxalate anion (C2O4_) are produced by some species of micro-organisms and these anions can form very insoluble salts with heavy metal ions which exhibit very small solubility products as noted by Veglio and Beolchini (1997). Copper phosphate precipitation occurring within the matrix of mycelia of the fungus Penicillium ochro-chloron after 4 days of incubation in shake flask cultures at pH 4, was demonstrated using scanning electron microscopy and energy dispersive x-ray microanalysis (Crusberg et al. 1994). Wrinkled 40-50 mm dia. spheres of insoluble copper phosphate, inferred from EDX analysis, are trapped within the mycelia of the fungus grown for 4 days in aerated cultures in the presence of 100mg l Cu2+. Penicilllium and Aspergillus have been shown to produce extracellular acid phosphatases which correlate with copper removal from solution (Haas et al. 1991...

T187m R227q F234l F194l

The HSD3B2 gene may play dual competing roles in prostate cancer etiology the enzyme product (noted above), is one of the two enzymes that irreversibly inactivates DHT in the prostate however, it is also responsible for production of the adrenal androgen androstenedione, which can undergo further conversion to T.41 A complex dinucleotide repeat polymorphism exists in intron 3, for which multiple alleles have been described with substantial variation in frequency across race ethnicity.75 In preliminary studies, several of these occur more frequently in prostate cancer patients than in healthy men.75 The number of candidate genes and their polymorphic variants in this pathway will continue to grow. The androgen-signaling pathway is highly intricate and complex, involving not just genes involved in androgen biosynthesis, transport, activation, and detoxification but also genes encoding coactivator proteins and a whole series

Pathophysiology of HHV6 reactivation in DRESS

Because several drugs associated with DRESS were metabolized to reactive oxidative metabolites, their role was evoked in the causation of the DRESS. Most previous studies done on lymphocytes from patients with DRESS, demonstrated a susceptibility to the toxic effects of oxidative drug metabolites (Shear et al., 1988 Green et al., 1995 Leeder, 1998). An increased risk associated with higher starting doses or concurrently administrated drugs in the case of lamotrigin or abacavir, for instance, brought clinical arguments. But genetic analysis of different genes, such as epoxide hydroxylase, implicated in detoxification did not corroborate previous studies (Gaedigk et al., 1994).

Yeast Copperiron Link

Mac1p and Ace1p are the two copper-responsive transcriptional activators in S. cerevisiae (2,9,10). Under copper-deficient conditions, Mac1p activates the expression of six genes, CTR1, CTR3, FRE1, FRE7, YFR055w, and YJL217w. With elevated copper levels, Ace1p activates the expression of copper-detoxification proteins, Cup1p and Crs5p.

Present Complaints

During 1998, Dianne was admitted for detoxification (one-week hospitalization) and subsequently treated in a day-care programme at an addiction treatment facility. She kept on drinking however, her depressive and anxiety symptoms only increased and her relationship with Mick deteriorated.

Disease Prevention

In any zebrafish colony, the appearance of disease could impact the whole colony, resulting even in death of the entire colony. Thus, disease prevention in a colony is critical. In an aging colony, this takes on a great urgency as one cannot readily replace the old fish that die and several years of work can be destroyed through introduction of a lethal pathogen or water impurity. Several filtration and detoxification methods are used in zebrafish facilities (Figure 27.1). These include methods such as ultraviolet filtration, to kill pathogenic bacteria from reaching the tank, and biological filters, to harvest bacteria that can denitrify the water. Accordingly, it is best to maintain an aging colony as an isolated colony in a barrier facility.

Metabolism of iron

Haeme biosynthesis occurs in all tissues, although the principal sites of synthesis are erythroid cells (-85 per cent) and hepatocytes (accounting for nearly all the rest of haeme synthesis). In hepatocytes, haeme is incorporated into cytochromes, in particular the P450 class which is important for detoxification. In erythroid cells, almost all of the haeme is synthesised for incorporation into haemoglobin. When the red cells mature, both haeme and haemoglobin synthesis cease. Normally after 120 days, senescent red blood cells are engulfed by macrophages. The globin is recycled or converted into amino acids, which in turn are recycled or catabolised as required. The haeme is oxidised by haemoxygenase, which results in the production of linear tetrapyrrole biliverdin, iron and carbon monoxide (CO). Most of the CO is excreted through the lungs, while the erythrocytic iron is then either stored as ferritin or released into the plasma via the iron export protein, ferroportin-1. The...

Effects of HBO

Even though the affinity for CO is less than for hemoglobin, dissociation of CO from other hemoproteins is slower due to the low tissue pO2 levels compared to the arterial pO2. This is exacerbated by the COHb-related reduced oxygen delivery. Accordingly, detoxification cannot begin until peripheral oxygen delivery is sufficient, i.e., once COHb dissociation is well on the way. This may also explain why detoxification of the other hemoproteins is delayed relative to haemoglobin.

Preventive Measures

After harvest, crop should not be allowed to overwinter in the field as well as subjected to bird and insect damage or mechanical damage. Grains should be cleaned and dried quickly to less than 10-13 moisture and stored in a clean area to avoid insect and rodent infestation (Trenholm et al. 1988). Postharvest mycotoxin contamination is prevalent in most tropical countries due to a hot, wet climate coupled with subadequate methods of harvesting, handling, and storage practices, which often lead to severe fungal growth and mycotoxin contamination of food and feed (Birzele et al. 2000 Phillips et al. 1994). Sometimes contaminated food has been diverted to animal feed to prevent economic losses and health concerns. However, this is not a solution to the contamination problem. Irradiation has been suggested as a possible means of controlling insect and microbial populations in stored food, and consequently, reducing the hazard of mycotoxin production under these conditions reviewed in...

Cancer

For a DNA-reactive chemical to induce a mutation, a number of conditions have to be met. Some are depicted in Figure 2. The first question is whether the phase I reaction of biotransformation results in the formation of a DNA-reactive intermediate. Secondly, does the reactive intermediate escape the various enzymatic and nonenzymatic detoxication processes Thirdly, does it react with DNA or with another molecule Although the reaction with water or other small molecules represents detoxification, the formation of protein adducts can be indirectly genotoxic, for instance by disturbing chromosome segregation or by cytotoxicity followed by regenerative hyperplasia. At all crossroads shown in Figure 2, numerous factors modulate the rate of the process (12). Genetic polymorphisms in tumor suppressor genes and proto-oncogenes can result in large differences in the susceptibility of individuals to develop cancer. As indicated in Figure 1, this could be caused by a reduction of the number of...

Discussion

There is considerable uncertainty on the subcellular site of hepatic injury caused by excess copper. From studies with Wilson's disease patients, it has been postulated that hepatic copper in the cytosol, which is predominant in the early stage of the disease, is toxic (22). In the liver of our LEC animals, copper levels were also fairly high in the cytosol before the onset of acute hepatitis however, the total of copper was bound to MT. Consistent with the role of MT in detoxifying metals, these findings do not support a prominent role of cytosolic copper in initiating hepatotoxicity. The assumption that the accumulation of copper in lysosomes represents a detoxification pathway (23) is questionable because findings in humans (1) and animals (24,25) suggest that, in particular, hepatocytes packed with copper-loaded lysosomes are the cells that undergo necrosis (26). Undoubtedly, the molecular association of copper within the lysosomes is of crucial importance with regard to its

Fro2 Fro2

Chlamydomonas does not seem to have genetic information for metallothioneins and probably uses only phytochelatins for detoxification of copper, cadmium, mercury, and other heavy metals (159-161), although it is possible that the metallothioneins of Chlamydomonas have not yet been discovered. Perhaps genomics will provide the answer to this question.

Pharmacokinetics

Nonlinearity in cancer dose-response relationships can result from saturation of a metabolic pathway. When an activation pathway is saturated, the dose response relationship can plateau at a level less than 100 lifetime risk, as in the frequently noted (1, 8, 89) case of vinyl chloride (88). When a detoxification or de-activation pathway saturates, the classic hockey stick dose-response curve can result. Data permitting, these effects can be formally taken into account through physiologically based pharmacokinetic (PBPK) modeling. The aim of the PBPK model in cancer risk prediction is to obtain a better estimate of effective dose than the administered dose, using model parameters measured in or estimated from experiments subsidiary to the bioassay. A cancer dose-response relationship for the bioassay or occupational dataset can then be expressed in terms of effective dose. If sufficient information and understanding permits the development of a PBPK model for the exposure circumstance...

Genetic Modifiers

To the phenotype of the proband, is consistent with the presence of either environmental or genetic modifiers. Genetic modifiers are probably more likely than shared environment to account for familial clustering of cancer sites in Ashkenazi Jewish mutation carriers, for example, since intrafamilial differences in environment are large in such families with recent immigration histories (4). Although there has also been considerable interest in finding genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers, the number of published studies is still fairly modest. The underlying reason for this may be that there is still a paucity of validated low-risk common alleles for breast or ovarian cancer in the general population, and until such alleles are identified, testing candidate single nucleotide polymorphisms (SNPs) as modifiers of BRCA1 and BRCA2 remains a fairly high-risk endeavor. Candidate modifier genes include those involved in detoxification of environmental...

Superoxide Dismutase

Catalase (EC 1.11.1.6) is a ubiquitous oxidoreductase that is present in most aerobic cells. Catalase (CAT) is involved in the detoxification of hydrogen peroxide (H2O2), a (ROS), into molecular oxygen and two molecules of water (22,23). CAT can be assayed directly by measuring the rate of appearance of molecular oxygen using a Clark-type electrode (124). Here, the enzyme extract is allowed to react with a known concentration of hydrogen peroxide. The formation of oxygen changes the potential of the Clark-type electrode which is proportional to the enzyme activity (124). Catalase activity has also been determined spectrophotometrically at 240 nm by monitoring the disappearance of hydrogen peroxide at pH 7.0 (125). Catalase also has a peroxidative activity which has been used to assay its activity by reaction with methanol in the presence of an optimal concentration of H2O2 (126,127). The formaldehyde produced is measured spectrophotometrically with (Purpald) as the chromogen, in which...

Pseudocheiridae

All have short, stocky limbs, short round ears, and tails that are bare at the lower side at least about the final third of their lengths. Many species have dorsal stripes, though these are not always clearly seen when the fur itself is rather dark. Fur colors differ from light gray cream, to orange, to dark brown. One species is greenish due to a mix of yellow, black, and white hairs. Internally, all species (including Petauroides) have a large cecum for fermenting their leaf-based diet, and their cheek-teeth are formed in the shape of cutting edges, scissorlike, to both cut and grind xerophytic leaves (e.g., Eucalyptus, which at least some species can detoxify).

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