Mammalian species

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

The female of mammalian species secretes a series of steroid hormones characterized by an aromatic A ring and the lack of a side chain at the 17 position. These compounds serve as regulators in the reproductive processes of the species. The name (estrogens) comes from the fact that in some lower animals the elaboration of this type of compound is directly involved with the phe-... 

It was known as early as 1927 that the adrenal glands of mammalian species secrete a series of substances essential to the survival of the individual. The hormonal nature of these secretions was suggested by the observation that extracts of the adrenal gland and more specifically of the outer portion of that organ (cortex) would ensure survival of animals whose adrenals had been excised. By 1943 no fewer than 28 steroids had been isolated from adrenal cortical extracts. These compounds were found to be involved in the regulation of such diverse and basic processes as electrolyte balance, carbohydrate metabolism, and resistance to trauma, to name only a few. 

Extracellular adenosine acts through a class of G protein-coupled receptors (GPCRs), defined across mammalian species as Ab A2a, A2B, and A3ARs (adenosine receptors). Adenosine has a cytoprotective role in the body, both in the periphery and in the central nervous system. Following binding of adenosine, or another naturally occurring agonist, the receptor... 

In humans as well as in other but not all mammalian species, kininogens are modified by posttranslational hydroxylation of a single proline residue of their kinin sequence, i.e. position 3 in bradykinin or position 4 in kallidin. Hydroxylation appears not to affect the specificity, affinity or intrinsic efficacy of the kinins. 

NOS (eNOS, NOS IH, NOS3). Classically, nNOS and eNOS were considered constitutive enzymes, whereas iNOS is cytokine-induced. Recent evidence suggests that nNOS and eNOS are also subject to important regulation of expression [1 ]. Within the human species, amino acid sequences of the three NOS isoforms share 52-58% identity. Each isoform is well conserved across mammalian species (>90% amino acid identity for nNOS and eNOS, >80% for iNOS). NOS enzymes exist in organisms as low as nematodes, protozoa, and even in plants (Fig. 1). 

Patel BA, Boudinot FD, Schinazi RF, Gallo JM, Chu CK (1990) Comparative pharmacokinetics and interspecies scaling of 3 -azido-3 -deoxythymidine (AZT) in several mammalian species. J Pharmacobiodyn 13 206-211... 

In summary, genotoxicity studies of endosulfan have provided evidence that this compound is mutagenic and clastogenic, and that it induces effects on cell cycle kinetics in two different mammalian species. However, some of these data may be suspect because some formulations of endosulfan have contained epichlorohydrin, a known genotoxic chemical, as a stabilizer (Hoechst 1990). It should be noted that humans may also be exposed to epichlorohydrin along with endosulfan. 

A considerable amount of the gold that accumulates in the kidneys and liver of mammalian species is bound to MTs. This buildup of gold in the kidneys is accompanied by elevated levels of renal copper to form copper-rich, gold-bearing MTs. In cell lines that overproduce MT, there is commonly a resistance to the cytotoxic effects of gold compounds. This resistance is also seen often in parent lines that have been repeatedly exposed to gold complexes. The mechanisms of resistance include but are not limited to enhanced biosynthesis of MT [102]. 

Distribution. Bone constitutes the largest fraction of the deposited body burden of americium in all mammalian species that have been studied. The mechanisms by which americium is taken up and retained in bone are only partially understood. The distribution of americium in bone initially is confined to bone surfaces, including endosteal and periosteal surfaces, and adjacent to vascular canals in cortical bone (Polig 1976 Priest et al. 1983, 1995 Schlenker et al. 1989). Deposition appears to be favored at sites of active... 

Mineral Oil Hydraulic Fluids and Polyalphaolefin Hydraulic Fluids. No literature was identified dealing with the bioavailability of chemicals in this category of hydraulic fluids. Because of this wide variation and the lack of any information in mammalian species, it is difficult to estimate bioavailability to humans. Additional research on the bioavailability of this category of hydraulic fluids would be valuable but may not be as high a priority as research on bioavailability issues for the phosphate ester-based hydraulic fluids. 

Synthetic pyrethroids are esters of specific acids (chrysantemic acid, halo-substituted chrysantemic acid, 2-[4-chlorophenyl]-3-methylbutyric acid) and alcohols (allethrone, 3-phenoxybenzyl alcohol) (Ray, 1991). They represent a group of insecticides largely used in agriculture and public health because of their relatively low toxicity to humans and mammalian species and their short environmental persistence. 

Initially, it was proposed that the 5-HTjb receptor is located exclusively in the brain of the rat and some other rodents, whereas the 5-HTid receptor, a close species homolog, is specific to the guinea pig and higher mammalian species, including humans (Waeber et al., 1989). However, recent studies have characterized the 5-HTiB receptor also in the human brain (Bidmon et al., 2001 Varnas et al., 2005). The 5-HT, B receptor is linked to the inhibition of adenylate cyclase, and is located at presynaptic (5-HT axon terminals) and postsynaptic... 

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