Chemical mediators

There is some evidence for chemically mediated endocrine disruption in amphibians. The egg yolk protein, vitellogenin, is inducible in amphibians by exposure to DDT. " Males of the short clawed toad Xenopus laevis given 250 fig/g or 1 fig/g o,p -DDT for seven days have been shown to produce vitellogenin, although the induction was less than that achieved by treatment with 1 fig/g of either 17/1-oestradiol or diethylstilboestrol. Research has also shown that endocrine disrupting chemicals can alter sex ratios in wild populations of certain species PCB congeners and organochlorine compounds have been linked with male domination of sex ratios in polluted compared to unpolluted sites. ... 

Evidence for chemically mediated disruption of thyroid function in wild reptile populations includes the finding of elevated thyroxine levels in male alligators from Lake Apopka, although a causal relationship with specific chemicals has not been established. ... 

Chemical-mediated immune suppression has been identified from the experimental study of several wildlife species. Harbour seals fed either chemically contaminated fish from the Wadden Sea or imcontaminated fish were found to have differing immune responses, with the exposed group showing lowered immune response to microbial infections and certain types of cancer. "" Mink fed fish taken from below a discharge point for bleached Kraft pulp mill effluent have also shown impaired immune function, " showing that the non-accnmillative chemicals in this effluent can actively disrupt endocrine associated functions. 

Horie and coworkers synthesized a series of flavones that showed promising inhibitory activity against archidonate 5-lipooxygenase. This enzyme is responsible for the initiation of bioactive leukotrienes that are chemical mediators of anaphylaxis and inflammation. Under standard K-R conditions o-hydroxyarylketone 66 and anhydride 67 in presence of the corresponding anhydride 68 delivered flavones 69 in yields of 42-65%. Subsequent hydrogenation of 69 afforded the flavone inhibitors 70. 

By the turn of the century the theory of chemical mediation of physiologic responses had gained some currency. There ensued in some laboratories an intense search for endogenous chemical modifiers of bodily responses. The first such agent to be isolated from mammalian tissue was the ubiquitous hormone, epinephrine—at that time known as adrenaline. This compound has played an important role in pharmacology as well as in medicinal chemistry. 

Fig. 2. IgG-mediated systemic versus local anaphylaxis, a IgG-mediated systemic anaphylaxis. When allergen-IgG immune complexes are formed in the circulation, basophils immediately capture them through IgG receptors on their surface and are activated to release PAF, that in turn act on vascular endothelial cells, leading to increased vascular permeability, b Passive cutaneous anaphylaxis. When allergen-IgG immune complexes are formed in the skin, they stimulate tissue-resident mast cells to release chemical mediators such as histamine, leading to local inflammation. 

Marone G, Triggiani M, Cirillo R, Vigorito C, Genovese A, Spampinato N, Condorelli M Chemical mediators and the human heart. Prog Biochem Pharmacol 1985 20 38. 

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

MTX caused a contraction of vascular smooth muscle and positive inotropic, positive chronotropic and arrhythmogenic effects on cardiac muscle. The effect of MTX was little affected by various receptor blockers, a Na channel blocker or a catecholamine depleting agent. Further, MTX had no effect on the enzymes which were related to Ca movements, such as Na , K -ATPase, cyclic AMP phosphodiesterase, and sarcoplasmic reticulum Ca -ATPase. These results would eliminate the possible involvement of an indirect action elicited by the release of chemical mediators and direct modifications of their receptors, Na channels, or various enzymes as a major mechanism of action of MTX. 

There are significant differences in the control experiments that are possible in each of these systems. Before the quantifier bio- can be applied, the possibility of abiotic alteration of the substrate during incubation must be eliminated or taken into consideration. Only the first design lends itself readily to this control. For experiments using cell suspensions, the obvious controls are incubation of the substrate in the absence of cells or using autoclaved cultures. Care should be exercised in the interpretation of the results, however, since some reactions may apparently be catalyzed by cell components in purely chemical reactions. The question may then legitimately be raised whether or not these are biochemically mediated. Two examples are given as illustration of apparently chemically mediated reactions, which have been referred to in Chapter 1 ... 

Lefcort H. (1996). Adaptive, chemically mediated fright response in tadpoles of the Southern Leopard frog, Rana utricularia. Copeia 2, 455-459. 

Timothy D. Moy. Emil Fischer as Chemical Mediator Science, Industry, and Government in World War One. Ambix. 36 (1989) 109-120. Source for German dependence on imported fertilizer. 

Tetratrophic interactions between a host plant, a phytophagous pest (primary host), a hymenopteran parasitoid or symbiont (secondary host) and a hymenopteran hyperparasitoid (which parasitizes the secondary host) are of considerable importance, because hyperparasitism can significantly reduce populations of economically beneficial parasitoids [11]. Hyperparasitoids use host-marking (=spacing) pheromones, sex pheromones [12], and host-detection cues [42], but they also show additional chemically mediated interactions with the other partners. These include detection of the primary host s secretions by the hyperparasitoid [43], detection of plant volatiles by the hyperparasitoid [44], and detection of the hyperparasitoid s secretions by the primary host [45] or by the secondary host. The latter causes the secondary host to avoid locations where the hyperparasitoid is foraging [46]. 

Parasitic hymenoptera hold promise in integrated pest management schemes, because they parasitize many economically important insect pests in a species-and stage-selective manner. The pheromones and kairomones of the parasitic hymenoptera have been studied for a long time, and there are many examples where there is evidence of chemical mediation of parasitoid behavior. This review emphasizes work done since the last major reviews [11, 12, 42] and, where it is available, on the primary bioassay-guided chemical identification of the semiochemical (Fig. 2 and Tables 3 and 4). 

With adequate resources and effort, the tools are available to chemically identify many more semiochemicals in Hymenoptera. Much is still to be understood about the chemically-mediated communication in this large and diverse insect order. In addition,because many hymenoptera are significant beneficial or pest insects, and the use of semiochemicals in the management and monitoring of insects is becoming standard, the identification of additional semiochemicals in Hymenoptera is an economically worthwhile endeavor. 

Schaffar B.P.H., Wolfbeis O.S., Chemically Mediated Fiber Optic Biosensors, chapter 8 in Biosensors Principles and Applications, L.J. Blum, P.R. Coulet (eds.), M. Dekker, New York, chapter 8, pp. 163-194 (1991). 

It is a measure of the changed outlook among neurophysiologists that it has been thought appropriate to include. ..[here]. .. a discussion on the nature of synaptic transmitter substances other than acetylcholine. A few years ago, the whole hypothesis of the chemical mediation of impulse transmission across central synapses was meeting so much opposition that the energies of those who supported it had to be concentrated on the claims of acetylcholine. ... 

Deposition of urate crystals in synovial fluid results in an inflammatory process involving chemical mediators that cause vasodilation, increased vascular permeability, complement activation, and chemotactic activity for polymorphonuclear leukocytes. Phagocytosis of urate crystals by leukocytes results in rapid lysis of cells and a discharge of proteolytic enzymes into the cytoplasm. The ensuing inflammatory reaction is associated with intense joint pain, erythema, warmth, and swelling. 

The most common etiology is exposure to environmental tobacco smoke, but other chronic inhalational exposures can also lead to COPD. Inhalation of noxious particles and gases stimulates the activation of neutrophils, macrophages, and CD8+ lymphocytes, which release a variety of chemical mediators, including tumor necrosis factor-a, interleukin-8, and leukotriene B4. These inflammatory cells and mediators lead to widespread destructive changes in the airways, pulmonary vasculature, and lung parenchyma. 

---