Lung solubility

Dimethyl-l,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide (41) is also an old product [7,11, 31] that has recently been found to react with GSH to give S-nitrosogluta-thione, NO and HNO [32]. It stimulates partially purified rat lung soluble guanylate cyclase, but not the heme-deficient enzyme. The activation is inhibited by ODQ. The product also displays significant vasodilator activity on rat thoracic aorta rings at nanomolar concentrations. Finally, [l,2,5]oxadiazolo[3,4-d]pyrimidine-5,7-dione 1-oxide derivatives (42, R,Ri=CH3,H) release NO, detected as nitrite, in the presence of thiols. A mechanism for this release has been proposed [33]. 

Ca reversibly inhibited both the basal and NO-stimulated forms of bovine lung soluble guanylate cyclase (Serfass et al. 2001). Inhibition was independent of the activator identity and concentration, revealing that Ca interacts with a site independent of the heme regulatory site. 

A PILOT STUDY OF THE LUNG SOLUBILITY OF RADIOACTIVE MATERIALS USED AT AWE... 

A Pilot Study of the Lung Solubility of Radioactive Materials Used at AWE... 

The relative toxicities of thallium compounds depend on their solubHities and valence states. Soluble univalent thallium compounds, eg, thaHous sulfate, acetate, and carbonate, are especiaHy toxic. They are rapidly and completely absorbed from the gastrointestinal tract, skin peritoneal cavity, and sites of subcutaneous and intramuscular injection. Tb allium is also rapidly absorbed from the mucous membranes of the respiratory tract, mouth, and lungs foHowing inhalation of soluble thallium salts. Insoluble compounds, eg, thaHous sulfide and iodide, are poorly absorbed by any route and are less toxic. 

Uranium can enter the human body orally, by inhalation, and through the skin and mucous membranes. Uranium compounds, both soluble and insoluble, ate absorbed most readily from the lungs. In the blood of exposed animals, uranium occurs in two forms in equiUbrium with each other as a nondiffusible complex with plasma proteins and as a diffusible bicarbonate complex (242). 

Toxicity. The toxicity of barium compounds depends on solubility (47—49). The free ion is readily absorbed from the lung and gastrointestinal tract. The mammalian intestinal mucosa is highly permeable to Ba " ions and is involved in the rapid flow of soluble barium salts into the blood. Barium is also deposited in the muscles where it remains for the first 30 h and then is slowly removed from the site (50). Very Httle is retained by the fiver, kidneys, or spleen and practically none by the brain, heart, and hair. 

The effects of this mixture of gases are insidious several hours may elapse before lung iiTitation develops. It is feebly irritant to the upper respiratory tract due to its relatively low solubility. 

Lead, because of its history as an air emission, has been fairly mobile and is particularly soluble in acid environments. Silver is used widely in the electronics industry. Intake of silver compounds can result in permanent discoloration of the skin and may result in damage to kidneys, lungs, mucous membranes, and other organs. 

The toxic effect depends both on lipid and blood solubility. I his will be illustrated with an example of anesthetic gases. The solubility of dinitrous oxide (N2O) in blood is very small therefore, it very quickly saturates in the blood, and its effect on the central nervous system is quick, but because N,0 is not highly lipid soluble, it does not cause deep anesthesia. Halothane and diethyl ether, in contrast, are very lipid soluble, and their solubility in the blood is also high. Thus, their saturation in the blood takes place slowly. For the same reason, the increase of tissue concentration is a slow process. On the other hand, the depression of the central nervous system may become deep, and may even cause death. During the elimination phase, the same processes occur in reverse order. N2O is rapidly eliminated whereas the elimination of halothane and diethyl ether is slow. In addition, only a small part of halothane and diethyl ether are eliminated via the lungs. They require first biotransformation and then elimination of the metabolites through the kidneys into the... 

Other important determinants of the effects of compounds, especially solvents, are their partition coefficients, e.g., blood-tissue partition coefficients, which determine the distribution of the compound in the body. The air-blood partition coefficient is also important for the absorption of a compound because it determines how quickly the compound can be absorbed from the airspace of the lungs into the circulation. An example of a compound that has a high air-blood partition coefficient is trichloroethane (low blood solubility) whereas most organic solvents (e.g., benzene analogues) have low air-blood partition coefficients (high blood solubility). 

Lungs also secrete nonvolatile compounds. Lipid-soluble compounds may thus be transported with the alveobronchotracheal mucus to the pharynx, where they are swallowed. They may then be excreted or reabsorbed. Particles are also removed by this mucociliary escalator. 

The interactions may be physicochemical without the participation of biological mechanisms for example, deep lung exposure to highly soluble irritative gases, such as sulfur dioxide, may become enhanced due to adsorption of the gas onto fine particles. Biological interactions may occur at all stages and body sites. For example, toxicity is increased when adverse effects are due to some reactive metabolic intermediate and exposure to another agent stimulates its metabolic activation (enzyme induction). 

The complex interplay of physicochemical and biological charactenstics that regulate the all important rate at which fluorocarbons may migrate within and finally leave the body, through the lungs and the skin, is not yet completely understood Certainly, variables are involved, such as vapor pressure, solubility m body tissues, molecular size and shape, lipid solubility, electron configuration, and critical soluQon temperatures [16, 17]... 

Opioids are easily absorbed subcutaneously and intramuscularly, as well as from the gastrointestinal tract, nasal mucosa (e.g., when heroin is used as snuff), and lung (e.g., when opium is smoked). About 90% of the excretion of morphine occurs during the first 24 hours, but traces are detectable in urine for more than 48 hours. Heroin (diacetyhnorphine) is hydrolyzed to monoacetylmorphine, which is then hydrolyzed to morphine. Morphine and monoacetylmorphine are responsible for the pharmacologic effects of heroin. Heroin produces effects more rapidly than morphine because it is more lipid soluble and therefore crosses the blood-brain barrier faster. In the urine, heroin is detected as free morphine and morphine glucuronide (Gutstein and Akil 2001 Jaffe et al. 2004). 

Their hydroxylated products are more water-soluble than their generally lipophilic substrates, facilitating excretion Liver contains highest amounts, but found In most If not all tissues. Including small Intestine, brain, and lung Located in the smooth endoplasmic reticulum or in mitochondria (steroidogenic hormones)... 

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