Selective tissue selectivity

Mechanisms of tissue/organ selectivity Tissue-selective activation of classic prodrugs Site-specific delivery of ad hoc chemical systems... 

Trichloroethanoic acid, CCI3COOH. A crystalline solid which rapidly absorbs water vapour m.p. 58°C, b.p. 196-5" C. Manufactured by the action of chlorine on ethanoic acid at 160°C in the presence of red phosphorus, sulphur or iodine. It is decomposed into chloroform and carbon dioxide by boiling water. It is a much stronger acid than either the mono- or the dichloro-acids and has been used to extract alkaloids and ascorbic acid from plant and animal tissues. It is a precipitant for proteins and may be used to test for the presence of albumin in urine. The sodium salt is used as a selective weedkiller. 

EST Expressed sequence tag. An EST is a partial sequence (typically less than 40C bases) selected from cDNA and used to identify genes expressed in a particuh tissue... 

Potcntiomctric Biosensors Potentiometric electrodes for the analysis of molecules of biochemical importance can be constructed in a fashion similar to that used for gas-sensing electrodes. The most common class of potentiometric biosensors are the so-called enzyme electrodes, in which an enzyme is trapped or immobilized at the surface of an ion-selective electrode. Reaction of the analyte with the enzyme produces a product whose concentration is monitored by the ion-selective electrode. Potentiometric biosensors have also been designed around other biologically active species, including antibodies, bacterial particles, tissue, and hormone receptors. 

The goal of the MRI scientist is to maximize the contrast-to-noise ratio between tissues. Examination of equation 13 reveals that by varyiag TR and TE, the clinician has a tremendous amount of flexibiHty to select the desired contrast between two tissues. 

Two ET GPCR subtypes, ET and ETg, have been cloned from human tissues. Both leceptois utilize IP /DAG for transduction. ET-1 and ET-2 have similai affinities for the ET subtype, whereas the affinity of ET-3 is much lower. All three peptides have similat affinities for the ETg subtype. Both receptor subtypes ate widely distributed, but ET receptors are more abundant in human heart, whereas ETg receptors constitute 70% of the ET receptors found in kidney. BQ 123 [136553-81 -6] cyclo-[D-Asp-Pro-D-Val-Leu-D-Trp], and ER 139317 (136) are selective ET antagonists. 

Three tachykinin GPCRs, NK, NK, and NK, have been identified and cloned. AH are coupled to phosphatidjhnositol hydrolysis. The NK receptor is selective for substance P (SP) and is relatively abundant in the brain, spinal cord, and peripheral tissues. The NK receptor is selective for NKA and is present in the gastrointestinal tract, urinary bladder, and adrenal gland but is low or absent in the CNS. The NIC receptor is selective for NKB and is present in low amounts in the gastrointestinal tract and urinary bladder, but is abundant in some areas of the CNS, ie, the spinal dorsal bom, soUtary nucleus, and laminae IV and V of the cortex with moderate amounts in the interpeduncular nucleus. Mismatches in the distribution of the tachykinins and tachykinin receptors suggest the possibility of additional tachykinin receptor subtypes. 

Dmg distribution into tissue reservoirs depends on the physicochemical properties of the dmg. Tissue reservoirs include fat, bone, and the principal body organs. Access of dmgs to these reservoirs depends on partition coefficient, charge or degree of ionization at physiological pH, and extent of protein binding. Thus, lipophilic molecules accumulate in fat reservoirs and this accumulation can alter considerably both the duration and the concentration—response curves of dmg action. Some dmgs may accumulate selectively in defined tissues, for example, the tetracycline antibiotics in bone (see Antibiotics,tetracyclines). 

Biomaterials for Cardiovascular Devices. Perhaps the most advanced field of biomaterials is that for cardiovascular devices. For several decades bodily parts have been replaced or repaired by direct substitution using natural tissue or selected synthetic materials. The development of implantable-grade synthetic polymers, such as siHcones and polyurethanes, has made possible the development of advanced cardiac assist devices (see... 

Implantable valves, particularly mechanical valves which continue to encroach on tissue valves, are unique. Methods such as valvuloplasty, mitral valve repair, or use of ultrasound are unlikely to reduce the number of valve replacements into the twenty-first century. Valve selection remains in the hands of the surgeon because of the critical nature of the procedure. If anything goes wrong, the result can be catastrophic to the patient. Cost of a valve, from 3000— 4000, is a relatively small part of the cost of open-heart surgery which can mn as high as 30,000. Growth of the cardiovascular valve market has slowed in the United States with the decline of the threat of rheumatic fever. 

Sulfite pulps have properties that are desirable for tissues and top quaHty, fine papers. Because sulfite pulping is not as versatile as kraft pulping, various options have been developed, and the choice of a specific process is dependent on individual mill situations. The unbleached pulp has high (60+) brightness compared to kraft pulp and is easily bleached. However, it is limited to select wood species. The heartwood of pine, Douglas fir, and cedars are not easily pulped. Additionally, pulps produced from hardwood have limited economic value because of low strength. 

Phosphorothioates generally protect normal tissues more than tumors. Tumor protection reported in some animal studies can pardy be explained by physiological effects of the particular dmgs, which are specific to rodents (4). WR-2721 does not appear to protect human and most animal tumors, apparentiy because of the low availabiUty of the dmg to tumor cells (4). Many tumors appear to have a reduced capillary density (44), which may mean that these tumors have altered levels of alkaline phosphatase, the enzyme that converts WR-2721 to WR-1065. A reduced abiUty of thiols to protect the hypoxic cells characteristic of many tumors may also contribute to their selectivity for normal tissues. The observation that WR-1065 protects cultured normal human fibroblasts, but not fibrosarcoma tumor cells, suggests that additional factors may contribute to the selectivity of radioprotection by WR-2721 m vivo (18). 

When administered intraperitoneaHy, sulfolane is excreted both unchanged and as 3-hydroxysulfolane [13031 -76-0] (24). Sulfolane injected intraperitoneaHy in mice and rats at 200—800 mg/kg at ambient temperatures of 15 and 25°C caused a dose-related inhibition of the metaboHc rate and hypoactivity, accompanied by hypothermia 60 min after injection. Despite their hypothermic condition these animals did not select a warm ambient temperature. Because sulfolane toxicity appears to be greater upon increased tissue temperature, the behavior of these animals seeking lower environmental temperature appears to enhance their chance of survival (25—28). 

The selective uptake of iodide ion by the thyroid gland is the basis of radioiodine treatment in hyperthyroidism, mainly with although various other radioactive isotopes ate also used (40,41). With a half-life of eight days, the decay of this isotope produces high energy P-particles which cause selective destmction within a 2 mm sphere of their origin. The y-rays also emitted are not absorbed by the thyroid tissue and are employed for external scanning. 

Toxicology. Inorganic tin and its compounds are generally of a low order of toxicity, largely because of the poor absorption and rapid excretion from the tissues of the metal (42—49). The acidity and alkalinity of their solutions make assessment of their parenteral toxicity difficult. The oral LD q values for selected inorganic tin compounds are Hsted in Table 2. It is estimated that the average U.S. daily intake of tin, which is mostly from processed foods, is 4 mg (see Food processing). 

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