Organ system studies hepatic

Sato et al. (1991) expanded their earlier PBPK model to account for differences in body weight, body fat content, and sex and applied it to predicting the effect of these factors on trichloroethylene metabolism and excretion. Their model consisted of seven compartments (lung, vessel rich tissue, vessel poor tissue, muscle, fat tissue, gastrointestinal system, and hepatic system) and made various assumptions about the metabolic pathways considered. First-order Michaelis-Menten kinetics were assumed for simplicity, and the first metabolic product was assumed to be chloral hydrate, which was then converted to TCA and trichloroethanol. Further assumptions were that metabolism was limited to the hepatic compartment and that tissue and organ volumes were related to body weight. The metabolic parameters, (the scaling constant for the maximum rate of metabolism) and (the Michaelis constant), were those determined for trichloroethylene in a study by Koizumi (1989) and are presented in Table 2-3. 

Several animal studies were located using the oral route for intermediate-duration and based on a combination of these studies, adverse effects have been reported in many organ systems. Hepatic, renal, and hematologic (Bombard et al. 1988 Carlson 1977 Hollingsworth et al. 1956 NTP 1987) effects have been the most consistent observations. The MRL was based on a minimal LOAEL of 188 mg/kg/day based on increased liver weights in rats. Since kidney effects involve hyaline droplet nephropathy, the renal effects were not considered to be a suitable basis for the MRL. 

Vinyl chloride has been associated with cancer in humans in a number of epidemiological studies. In four facilities engaged in the polymerization of vinyl chloride for at least 15 years, workers exposed for at least 5 years had a significant number of excess deaths due to malignant neoplasms (35 deaths observed, 23.5 expected). The excesses were found for four organ systems CNS (3 observed, 0.9 expected), respiratory system (12 observed, 7.7 expected) hepatic system (7 observed, 0.6 expected), and lymphatic and hematopoietic systems (4 observed, 2.5 expected). 

In long-term therapy, perform periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies. 

As inflammation is an integral part of many disorders that affect different organs, the following section is organized by organ systems. To date, most studies have investigated the impact of inflammation on hepatic gene expression. In addition, we will also discuss the impact of inflammation on the blood-brain barrier, the intestine, and the kidney. 

In one of the founding studies in immunotoxicology, Friend and Trainer [77] demonstrated that exposure to polychlorinated biphenyls (PCBs) increased mortality of mallard (Anas platyrhynchos) ducklings challenged with duck hepatitis virus. Since then the field of avian immunotoxicology has expanded to show that both the structure and function of the avian immune system often is affected by a diverse array of environmental contaminants, including heavy metals, pesticides, petroleum hydrocarbons, and organic industrial chemicals. Wild birds have proven to be excellent sentinel species for assess-... 

Although there are no data from human studies that indicate that hepatic effects occur in humans exposed to heptachlor, the animal studies indicate that the liver is a target organ for this chemical and is more sensitive to low doses than the neurological system. Decreased glycogen, increased cholesterol, GOT, and AP enzyme levels, and increased liver weight were reported in mice fed heptachlor at 0.5 mg/kg/day. In contrast, neurological effects such as convulsions were observed in a cow fed 2.5 mg/kg/day heptachlor daily for 15 days (Buck et al. 1959). Increased liver enzymes could indicate exposure to heptachlor, but this would not be a marker specific to this chemical. Refer to Section 2.2 for a detailed discussion of the effects caused by heptachlor and heptachlor epoxide. 

Until recently, previous studies for continuous monitoring of hepatic function with ICG utilized the absorption mode. However, new studies demonstrate that the highly sensitive fluorescence technique can equally be used [148-150]. In addition to high sensitivity, in-depth analysis of the emission, excitation and polarization properties of fluorescence spectroscopy furnishes additional functional information about the dye molecule. In this system, the fluorescence profile emanating from the clearance of injected biocompatible dye is monitored with a small photodetector. Fig. 8 shows the in vivo fluorescence detection apparatus developed for continuous monitoring of organ functions [147,148]. 

The existing data indicate that, in humans, respiratory and hepatic effects result from inhalation exposure and that the liver, hematopoietic system and cardiovascular system are the target organs following intravenous injection of Thorotrast. Studies in animals have not reported effects in these... 

The first applications of solid phase synthesis were to peptides, hence it is no surprise that there have been several reports of HRMAS studies of peptide systems attached to a support. One of the earliest reports of HRMAS in a supported sample was that of Wang-bound lysine, whose structure was determined by TOCSY and HMQC HRMAS NMR.38 More recently, HRMAS NMR has been used to identify several peptidomimetic inhibitors of hepatitis C virus NS3 protease while on the resin.79 However, it is perhaps a bit surprising that more has not been made of HRMAS in attacking problems of relevance to peptide synthesis, although most recent interest is moving that way. Combinatorial chemistry and solid phase organic chemistry has been a much more active area using HRMAS techniques. 

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