Activity in Vivo

In spite of the rationale on which the testing of dyestuffs as antibiotics rested subsequent research re vealed that the antibacterial properties of Prontosil had nothing at all to do with its being a dye In the body Prontosil undergoes a reductive cleavage of its azo linkage to form sulfanilamide which is the sub stance actually responsible for the observed biological activity This is why Prontosil is active in vivo but not in vitro... 

Two fundamental questions have emerged from these studies, ie, to what extent are agonists and antagonists binding similarly or differendy to the respective receptors, and can inhibitory compounds be developed that are active in vivo in humans as well as in vitro. An oxytocia antagonist that can block premature uterine contractions presents a promising example of the clinical utihty of such stmctures (47). Both linear as well as bicycHc modifications of these hormones also have provided new antagonist stmctures. 

Whereas over 200 plant constituents are reported to have antiviral activity, as determined by in vitro methods, only 31 compounds have shown antiviral activity in vivo (19). Immunotherapeutic activity has not been determined. 

Dihydroxyvitamin (283) is the endogenous ligand for the vitamin receptor (VDR). It modulates genomic function in a tissue and developmentaHy specific manner and affects ceU proliferation, differentiation, and mineral homeostasis (74). Vitamin mobilizes calcium from the bone to maintain plasma Ca " levels. Vitamin and VDR are present in the CNS where they may play a role in regulating Ca " homeostasis. Vitamin D has potent immunomodulatory activity in vivo. 

Basic FGF can also stimulate murine hemopoietic progenitors in vitro. It is synergistic with hemopoietic growth factors such as GM-CSF, EPO, and Meg-CSF and has radioprotective activity in vivo, increasing the number of day-9 and day-12 CFU-S from lethaUy irradiated animals (195). Furthermore, b-FGF combiaed with GM-CSF protects against the killing of murine and human CFU-GM exposed to radiation in vitro (195). 

Similar stmcture activity relationships were found in the 4 -alkyl analogues of clindamycin (87). The de- /V-methylclindamycin intermediates including de- /V-methylclindamycin itself, but unlike de-/V-methyllincomycin, are also highly active antibacterially. In addition, they are active in vivo as antknalarial agents (66—68). 

The 3, 5 -cyclic phosphate of ara-C has shown significant antiviral activity in vivo with an efficacy greater than that exhibited by ara-C itself (35). It was speculated that the 3, 5 -cycHc phosphate moiety may inhibit the deamination of ara-C, thus causiag the iacreased in vivo potency. A number of derivatives of ara-C have been prepared ia an effort to improve on antiviral activity and to reduce the toxicity. One such derivative is 2 - uoro-5-iodo-l-p-D-arabiQofuranosylcytosiae [69123-90-6] (FIAC, 17), synthesized (36) ia 1979. It is active against certain DNA vimses. FIAC,... 

In contrast to heparin, the coumarinic acid anticoagulants are inactive in vitw ]6k.e heparin they are active in vivo. The phenylindanedione-type compounds (7) (36) and warfarin (2) produce their in vivo inhibitory effect on the coagulation system by competitively antagonizing the normal activity of vitamin (8) (37—44). 

It was agreed at the workshop that endocrine disrupting activity could only be adequately defined in terms of effects in intact animals, be they juvenile or adult, or in the offspring of exposed parents. For many chemicals, evidence of endocrine disrupting activity has been obtained only by the use of in vitro models, such as hormone binding assays. It was accepted, therefore, that chemicals active in such models should be considered only as potential EDs and should be distinguished from those established as active in vivo. For such chemicals, an alternative definition was recommended ... 

Costa JJ, Demetri GD, Harris TJ. Dvorak AM. Hayes DF, Merica EA, Menchaca DM. Gringeri AJ. Schwartz LB, Galli SJ Recombinant human stem cell factor (kit ligand) promotes human mast cell and melanocyte hyperplasia and functional activation in vivo. J Exp Med 1996 183 2681-2686. 

Immediate hypersensitivity reactions to RCM are associated with histamine release from basophils and mast cells [27], and extensive mast cell activation in vivo associated with clinical symptoms has been demonstrated by Earoche et al. [31]. Patients with hypersensitivity reactions after contrast medium exposure had increased plasma levels of both histamine and tryptase, and levels correlated with severity. Also other investigators have reported high levels of tryptase in connection with severe or fatal reactions [21, 33]. 

Studies on the penicillin. Relation between the growth inhibitory effect in vitro and the protective activity in vivo," H. Umezawa and T. Takeuchi, J. Penicillin, 1 (1947) 14-18 spoken at the Penicillin Committee in Jan., 1945. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

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