Human body tissues, distribution

The distribution of chromium in human body tissue after acute oral exposure was determined in the case of a 14-year-old boy who ingested 7.5 mg chromium(VI)/kg as potassium dichromate. Despite extensive treatment by dialysis and the use of the chelating agent British antilewisite, the boy died eight days after admission to the hospital. Upon autopsy, the chromium concentrations were as follows liver,... 

Distribution of Pesticide Residues in Human Body Tissues from Montgomery County, Ohio... 

Zinc. The 2—3 g of zinc in the human body are widely distributed in every tissue and tissue duid (90—92). About 90 wt % is in muscle and bone unusually high concentrations are in the choroid of the eye and in the prostate gland (93). Almost all of the zinc in the blood is associated with carbonic anhydrase in the erythrocytes (94). Zinc is concentrated in nucleic acids (90), and found in the nuclear, mitochondrial, and supernatant fractions of all cells. 

Manganese. The adult human body contains ca 10—20 mg of manganese (124,125), widely distributed throughout the body. The largest Mg " concentration is in the mitochondria of the soft tissues, especially in the Hver, pancreas, and kidneys (124,126). Manganese concentration in bone varies widely with dietary intake (126) (see Table 10). 

The average adult human body contains 22 mg Ba, of which 93% is present in bone (47). The remainder is widely distributed throughout the soft tissues of the body in very low concentrations. Accumulation of barium also takes place in the pigmented parts of the eyes. 

The absorption, distribution, and accumulation of lead in the human body may be represented by a three-part model (6). The first part consists of red blood cells, which move the lead to the other two parts, soft tissue and bone. The blood cells and soft tissue, represented by the liver and kidney, constitute the mobile part of the lead body burden, which can fluctuate depending on the length of exposure to the pollutant. Lead accumulation over a long period of time occurs in the bones, which store up to 95% of the total body burden. However, the lead in soft tissue represents a potentially greater toxicological hazard and is the more important component of the lead body burden. Lead measured in the urine has been found to be a good index of the amount of mobile lead in the body. The majority of lead is eliminated from the body in the urine and feces, with smaller amounts removed by sweat, hair, and nails. 

The term vitamin E describes a family of eight antioxidants, four tocopherols, alpha (a), beta ((3), gamma (y) and delta (8), and four tocotrienols (also a, (3, y, and 8). a-Tocopherol is present in nature in only one form, RRR a-tocopherol. The chemical synthesis of a-tocopherol results in eight different forms (SRR, SSR, SRS, SSS, RSR, RRS, RSS, RRR), only one of which is RRR a-tocopherol. These forms differ in that they can be right (R) or left (S) at three different places in the a-tocopherol molecule. RRR a-tocopherol is the only form of vitamin E that is actively maintained in the human body and is therefore the form of vitamin E found in the largest quantities in the blood and tissue. A protein synthesized in the liver (a-TTP alpha-tocopherol transfer protein) preferentially selects the natural form of vitamin E (RRR a-tocopherol) for distribution to the tissues. However, the mechanisms for the regulation of vitamin E in tissues are not known... 

Of the thousands of different enzymes present in the human body, those that fulfill functions indispensable to cell vitality are present throughout the body tissues. Other enzymes or isozymes are expressed only in specific cell types, during certain periods of development, or in response to specific physiologic or pathophysiologic changes. Analysis of the presence and distribution of enzymes and isozymes— whose expression is normally tissue-, time-, or circumstance-specific—often aids diagnosis. 

Several studies of tissue distribution in humans after inhalation exposure to trichloroethylene report levels in the blood (Astrand and Ovrum 1976 Monster et al. 1976 Muller et al. 1974). Once in the bloodstream, trichloroethylene may be transported rapidly to various tissues where it will likely be metabolized. Trichloroethylene was detected in the blood of babies at birth after the mothers had received trichloroethylene anesthesia (Laham 1970), and detectable levels (concentrations not reported) have been found in the breast milk of mothers living in urban areas (Pellizzari et al. 1982). Post-mortem analyses of human tissue from persons with unspecified exposure revealed detectable levels of trichloroethylene (<1-32 pg/kg wet tissue) in most organs (McConnell et al. 1975). The relative proportions varied among individuals, but the major sites of distribution appeared to be body fat and the liver. 

The overall results and individual PBPK models for trichloroethylene are discussed in this section in terms of their use in risk assessment, tissue dosimetry, and dose, route, and species extrapolations. Several PBPK models have been developed for inhaled trichloroethylene. In an early model by Fernandez et al. (1977), the human body was divided into three major compartments or tissue groups the vessel-rich group (VRG), muscle group (MG), and adipose tissue (fat) group (FG). The distribution of trichloroethylene in these... 

Microspheres made of various polymers biodegradable to nonharm-ful compounds that could be metabolized and/or removed from organisms found many applications in medicine as carriers of drugs or other bioactive compounds [1 ]. Besides chemical composition there are also other properties of microspheres that are of primary importance to their medical applications. In particular, average diameters and diameter distributions illustrated in Table 1 based on data published in [5] are the relationship between the diameters of microspheres and their localization in various cells and tissues of the human body. 

Scientific knowledge concerning histamine has developed in stages since it was first synthesized in 1907 (1 ). It was isolated from an ergot preparation by Barger and Dale in 1910 ( ) and its dramatic pharmacological effects demonstrated. Dale then established that histamine was a normal constitutent of mammalian tissue and widely distributed throughout the human body ( ). 

An understanding of the pharmacology of nicotine and how nicotine produces addiction and influences smoking behavior provides a necessary basis for therapeutic advances in smoking cessation interventions. This chapter provides a review of several aspects of the human pharmacology of nicotine. These include the presence and levels of nicotine and related alkaloids in tobacco products, the absorption of nicotine from tobacco products and nicotine medications, the distribution of nicotine in body tissues, the metabolism and renal excretion of nicotine, nicotine and cotinine blood levels during tobacco use or nicotine replacement therapy, and biomarkers of nicotine exposure. For more details and references on the pharmacokinetics and metabolism of nicotine, the reader is referred to Hukkanen et al. (2005c). 

Absorption, Distribution, Metabolism, and Excretion. Levels of cresols in blood were obtained from a single case report of a dermally exposed human (Green 1975). Data on the toxicokinetics of cresols in animals were contained in two acute oral studies that provided only limited quantitative information on the absorption, metabolism, and excretion of cresols (Bray et al. 1950 Williams 1938). A more complete oral toxicokinetics study, in addition to studies using dermal and inhalation exposure, would provide data that could be used to develop predictive pharmacokinetic models for cresols. Inclusion of several dose levels and exposure durations in these studies would provide a more complete picture of the toxicokinetics of cresols and allow a more accurate route by route comparison, because it would allow detection of saturation effects. Studies of the tissue distribution of cresols in the body might help identify possible target organs. 

PAM has been studied extensively by pharmacokinetic means, and data are available on its absorption, tissue distribution, blood concentration, and elimination by humans and animals. Although it has been given as various salts, the particular form administered is of no consequence once the material is absorbed and dissociated into the cation by body fluids.61 100,106... 

The analysis of several tissues of humans who died following acute oral poisoning with 1,2-dichloroethane showed that 1,2-dichloroethane is widely distributed throughout the human body. Concentrations ranged from 1 to 50 mg/kg in the spleen and 100 to 1000 mg/kg in the stomach levels in the liver and kidney were approximately 10 times lower than those in the stomach (Luznikov et al., 1985). 

Proteins, on a weight basis, are second only to water in their presence in the human body. If the factor of water is discounted, then about 50% of the body s dry weight is made up of numerous protein substances, distributed about as follows 33% in muscles 20% in bones and cartilage 10% in skin the remaining 37% in numerous other body tissues. With exception of the urine and bile in the normal healthy individual, all other body fluids contain from small to relatively large portions of protein substances. 

As illustrated in the previous chapter, the human body can be exposed to a variety of toxicants that may be present in various environmental media such as air, soil, water, or food. However, just simply being exposed to these hazardous chemicals does not necessarily translate into a toxicological response. The mammalian body has several inherent defense mechanisms and membrane barriers that tend to prevent the entry or absorption and distribution of these toxicants once an exposure event has occurred. However, if the toxicant is readily absorbed into the body, there are still other anatomical and physiological barriers that may prevent distribution to the target tissue to elicit a toxic response. As the toxicological response is often related to the exposed dose, interactions between the toxicant and the body s barriers and defense mechanisms will have an effect on toxicant movement in the body, and ultimately modulate the rate and extent of toxicant absorption and distribution to the target tissue. 

Carrier, G., R.C. Brunet, and J. Brodeur. 1995. Modeling of the toxicokinetics of polychlorinated dibenzo-p-dioxins and dibenzofurans in mammalians, including humans. I. Nonlinear distribution of PCDD/PCDF body burden between liver and adipose tissues. Toxicol. Appl. Pharmacol. 131(2) 253-266. 

The steady-state volume of distribution is 12 1/kg. Donepezil hydrochloride is approximately 96% bound to human plasma proteins. The distribution of donepezil hydrochloride in various body tissues has not been definitively studied. However, in a mass balance study conducted in healthy male volunteers, 240 h after the administration of a single 5 mg dose of 14C-labeled donepezil hydrochloride, approximately 28% of the label remained unrecovered. This suggests that donepezil and/or its metabolites may persist in the body for more than 10 days. 

The standard patient has a mass of 70 kg, and the density of the human body is very close to 1 g/mL. What is the body volume of the standard patient in liters Based on this volume and using the data in Table 3.1, determine the molar concentration of iron in the body. Assume all the iron in the body is evenly distributed throughout all tissues. Repeat the calculation on selenium, an element involved in certain oxidation-reduction processes in the body. The lesson of this question is that trace elements can be very trace indeed. 

Salicylamide is readily absorbed from the gastrointestinal tract and distributed to all body tissues but the drug does not bind appreciably to plasma proteins. Several studies had been reported in literatures dealing with the absorption of salicylamide and its plasma concentration (20), (21), (22), (23). It is rapidly excreted in the urine mainly as the glucuronide and sulphate conjugates. Salicylamide is metabolized in human entirely as shown in Scheme 1. 

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