Other Tissues

Macrophages from mouse bone marrow showed increased PGE production when incubated with ascorbic acid (Siegel and Morton, 1984). In contrast, in renal medulla, ascorbic acid inhibited PG synthesis (Zenser and Davis, 1978). 

In corneal tissue, ascorbic acid was able to inhibit the activity of lipoxygenase and reduce the production of 12-hydroxyeicosatetraeroic acid, the major lipoxygenase product produced by the cornea (Williams and Paterson, 1986). 

It is apparent that the effects of ascorbic acid on the metabolism of EFAs and PGs are complex and relatively poorly defined. There seem to be highly variable actions depending in part on the concentration, incubation, or administration conditions and 

However, if the effect is particularly specific for PGEj, as indicated by those studies that have distinguished between PGE, and PGE2 (Manku et ai, 1979 Srivastava, 1985), then this action could contribute to an understanding of many of the known effects of vitamin C in various tissues (Horrobin et al.y 1979). These consequences of vitamin C deficiency include the disruption of collagen synthesis, susceptibility to infections, elevated cholesterol levels, and resistance to insulin. In each of these situations, PGE is known to have an action that is similar to that of vitamin C supplementation in the vitamin C-deficient state. It is therefore possible that ascorbate stimulation of PGEj formation could contribute to these well-known actions of ascorbic acid (Horrobin et ai, 1979). However, proof of the validity of this concept will require a great deal more experimental work. 

Aikawa, T., Sekizawa, K., Itabashi, S., Sasaki, H., and Takishima, T., 1990, Inhibitory actions of prostaglandin El on non-adrenergic non-cholinergic contraction in guinea pig bronchi, Br. J. Pharmacol. 101 13-14. 

By taking into account the existence of silver nanoparticle-impregnated catheters for clinical use, hemocompatibility becomes a top safety concern. Previous reports have suggested that nanoparticles present in the blood were associated with thrombosis and the activation of immunological reactions. Various studies have provided evidence that exposme to ambient ultrafine particles elicits an inflammatory response in vascular endothelial cells and blood cells [104, 105]. In the case of silver, a recent study revealed that silver nanoparticles could greatly enhance the electron-transfer reactivity of myoglobin [106]. 

The recent identification of the cytotoxicity of silver nanoparticles towards a spermatogonial stem cell tine has aroused great concern over the biosafety of nanomaterials [107]. As discussed previously, the liver appears to be an eventual accumulation site for circulatory silver nanoparticles, and similar patterns of cytotoxicity for silver nanoparticles (decreased mitochondrial function, lactate dehydrogenase (LDH) leakage and abnormal cell morphologies) were observed in vitro. Nonetheless, during other experiments using nanosilver, a variety of 

---

Estrogens coordinate the systemic response during the ovulatory cycle, including the growth and maintenance of the reproductive tract, pituitary, breasts, and other tissues. Estrogens are also responsible for maturation of the skeleton and development of female secondary sex characteristics when females enter puberty. The other important functions of estrogens include modulation of many metaboHc processes (76). 

Another aspect of the hydrolysis of hydrides is the alkalinity that results, especially from alkaU metal and alkaline-earth hydrides. This alkalinity can cause chemical bums in skin and other tissues. Affected skin areas should be flooded with copious amounts of water. 

Iron is indispensable in the human body (see Mineral nutrients). The average adult body contains 3 grams of iron. About 65% is found in hemoglobin, which carries oxygen from the lungs to the various parts of the body. Iron is also needed for the proper functioning of cells, muscles, and other tissues (4). 

Specific barriers may serve to limit dmg distribution. The placental barrier is of obvious importance to dmg action in the fetus. Dmg transfers across the placenta primarily by Hpid solubiHty. Hence, this barrier is not particularly restrictive. Similarly, the Hpid solubiHty of a dmg is a primary deterrninant in access to the brain and cerebrospinal fluid. Generally, hydrophilic or charged dmgs can also penetrate to these latter areas, but the result is slow and incomplete. The blood brain barrier is composed of cells having tight junctions which are much less permeable to solutes than are the endotheHal cells of other tissues. 

Desflurane is less potent than the other fluorinated anesthetics having MAC values of 5.7 to 8.9% in animals (76,85), and 6% to 7.25% in surgical patients. The respiratory effects are similar to isoflurane. Heart rate is somewhat increased and blood pressure decreased with increasing concentrations. Cardiac output remains fairly stable. Desflurane does not sensitize the myocardium to epinephrine relative to isoflurane (86). EEG effects are similar to isoflurane and muscle relaxation is satisfactory (87). Desflurane is not metabolized to any significant extent (88,89) as levels of fluoride ion in the semm and urine are not increased even after prolonged exposure. Desflurane appears to offer advantages over sevoflurane and other inhaled anesthetics because of its limited solubiHty in blood and other tissues. It is the least metabolized of current agents. 

The only commonly used radioisotope in this class is used in small (- IS.S MBq (500 -lCi) injected dose) quantities as a diagnostic for the evaluation of thyroid function. The compound is adininistered as Nal and these procedures are only possible owing to the favorable biological distribution of iodide. Up to 25% of the entire injected dose of iodide is accumulated in the thyroid with a very slow washout the rest is rapidly excreted in the urine. No other compound exhibits so high a ratio of concentration in a target tissue to that of other tissues. 

Interleukin-1 OC and (3. IL-1 has radioprotective activity toward BM and other tissues (151,164). IL-1 is produced in response to endotoxin, other cytokines, and microbial and viral agents, primarily by monocytes and macrophages. Other nucleated cells can also produce it. IL-1 appears to play an important role in the regulation of normal hemopoiesis directly by stimulating the most primitive stem cells and indirectly by stimulating other hemopoietic factors, including G-CSF, GM-CSF, M-CSF, and IL-6. 

Ascorbic acid is involved in carnitine biosynthesis. Carnitine (y-amino-P-hydroxybutyric acid, trimethylbetaine) (30) is a component of heart muscle, skeletal tissue, Uver and other tissues. It is involved in the transport of fatty acids into mitochondria, where they are oxidized to provide energy for the ceU and animal. It is synthesized in animals from lysine and methionine by two hydroxylases, both containing ferrous iron and L-ascorbic acid. Ascorbic acid donates electrons to the enzymes involved in the metabohsm of L-tyrosine, cholesterol, and histamine (128). 

In humans, thiamine is both actively and passively absorbed to a limited level in the intestines, is transported as the free vitamin, is then taken up in actively metabolizing tissues, and is converted to the phosphate esters via ubiquitous thiamine kinases. During thiamine deficiency all tissues stores are readily mobilhed. Because depletion of thiamine levels in erythrocytes parallels that of other tissues, erythrocyte thiamine levels ate used to quantitate severity of the deficiency. As deficiency progresses, thiamine becomes indetectable in the urine, the primary excretory route for this vitamin and its metaboHtes. Six major metaboHtes, of more than 20 total, have been characterized from human urine, including thiamine fragments (7,8), and the corresponding carboxyHc acids (1,37,38). 

The GI absorption of the dmg after po adrninistration is slow and variable with estimates ranging from 20—55%. Once absorbed, 96% of the dmg is bound to plasma proteins and other tissues on the body. Whereas peak plasma concentrations may be achieved in 3—7 h, the onset of antiarrhythmic action may occur in 2—3 days or more. This may result, in part, from distribution to and concentration of the dmg in adipose tissue, Hver, spleen, and lungs. Therapeutic plasma concentrations are 1—2 p.g/mL, although there appears to be no correlation between plasma concentration and antiarrhythmic activity. The plasma half-life after discontinuation of the dmg varies from 13—103 days. The dmg is metabolized in the Hver and the principal metaboHte is desethylamiodarone. The primary route of elimination is through the bile. Less than 1% of the unchanged dmg is excreted in the urine. The dmg can also be eliminated in breast milk and through the skin (1,2). 

Organic Bases — (such as amines, RNHj) are weak bases but can be corrosive to skin or other tissue. 

The livers and intestines of animals are the primary sources of circulating lipids. Chylomicrons carry triacylglycerol and cholesterol esters from the intestines to other tissues, and VLDLs carry lipid from liver, as shown in Figure 25.38. At... 

One of the first prodrugs, aspirin, is cleaved to the active agent, salcylic acid, in the liver as well as various other tissues. Despite the advent of numerous newer agents for the alleviation of the pain and inflammation characteristic of inflammatory diseases, aspirin remains the most widely used drug for this 108... 

There is weak expression of PPARy in muscle, liver and other tissues, enabling TZDs to support the effects of insulin in these tissues, notably increased glucose uptake in muscle and reduced glucose production in liver. TZDs may also affect nutrient metabolism by skeletal muscle through a direct mitochondrial action that is independent of PPARy. 

Excitability refers to the capacity of nerves and other tissues (e.g. cardiac), as well as individual cells, to generate and sometimes propagate action potentials, signals that serve to control intracellular processes, such as muscle contraction or hormone secretion, and to allow for long- and short-distance communication within the organism. Examples of excitable cells and tissues include neurons, muscle and endocrine tissues. Examples of nonexcitable cells and tissues include blood cells, most epithelial and connective tissues. 

Originally described in the immune system, NFAT proteins comprise a family of transcriptional factors that play key roles in many cellular processes that control not only immune responses but also the development, regulation, and differentiation of many other tissues. Activation of NFAT proteins results in the expression of specific sets of genes that regulate multiple cell functions [1,2]. 

The development of drugs that block Calcineuiin phosphatase activity has allowed successful prevention of graft rejection. Due to the key role that NFAT has in T-cell activation, these inhibitors behave as potent immunosuppressors. Nevertheless, the important roles that NFAT proteins have in other tissues suggest that exploring the use of similar drugs in other pathological contexts may be clinically and therapeutically relevant. 

---