Nonspecific biological activities

To identify the compound as a member of a set that is not desired. These classes might include common interfering groups of compounds such as tannins and polyphenols, fatty acids, or proteins, that may show nonspecific biological activity. The natural product might be one or a mixture of such compounds and may even include novel compoimds. 

It is this relationship to physicochemical properties like partition coefficients, molar refractivities, and steric properties that allows a quantitative description of (most often nonspecific) biological activities within chemically closely related series. 

Papaverine (107) is among the host of minor alkaloids that have been isolated from opium. The compound is distinct in its biologic activity from many of the other opium constituents in that it does not exhibit any analgesic activity. Instead, papaverine acts as a nonspecific spasmolytic agent. As such, it has found... 

Before the first indication of the existence of cannabinoid receptors, the prevailing theory on the mechanism of cannabinoid activity was that cannabinoids exert their effects by nonspecific interactions with cell membrane lipids (Makriyannis, 1990). Such interactions can increase the membrane fluidity, perturb the lipid bilayer and concomitantly alter the function of membrane-associated proteins (Loh, 1980). A plethora of experimental evidence suggests that cannabinoids interact with membrane lipids and modify the properties of membranes. However, the relevance of these phenomena to biological activities is still only, at best, correlative. An important conundrum associated with the membrane theories of cannabinoid activity is uncertainty over whether cannabinoids can achieve in vivo membrane concentrations comparable to the relatively high concentrations used in in vitro biophysical studies (Makriyannis, 1995). It may be possible that local high concentrations are attainable under certain physiological circumstances, and, if so, some of the cannabinoid activities may indeed be mediated through membrane perturbation. 

Objectives Optimize biological activity of drugs Find new active lead compounds Characteristics Response in isolated systems Effects are specific and well defined Specific mechanism of action Receptor is known in most cases Techniques Hansch Approach Multivariate Analysis Computerized molecular modeling Estimate rates of fate processes Analyze Processes Whole organism response Net effects (mortality growth, etc.) Specific nonspecific mechanisms Receptor unknown in most cases Hansch Approach Multivariate Analysis Molecular modeling not applied... 

To determine the F/P ratio of the labeled protein, measure the absorbance of the purified preparation at 345 and 280 nm. Ratios of 345 /280 nm within the range 0.3 to 0.8 usually result in fluorescent conjugates with a good balance of high-intensity luminescence, low nonspecific binding, and excellent retention of biological activity within the protein component. 

The avidin-biotin immobilization method maintains the biological activity of the receptor molecules. Besides the biocompatibility of the procedure, the surface geometry of these films provides high accessibility of the immobilized biomolecules. In addition, the avidin molecules form a passivation layer on the transducer surface that prevents nonspecific adsorption of proteins on the surface. In contrast with conventional grafting or affinity binding, this step-by-step approach can also be applied to the preparation of assemblies containing multilayers of biological molecules [42],... 

Th2 cytokine IL-10 is an antiinflammatory cytokine that suppresses the secretion of proinflammatory cytokines (Dll), allergen-induced airway inflammation, and nonspecific airway responsiveness (T9). IL-13 shares a receptor component, signaling pathways, and many biological activities with IL-4. In fact, IL-13 is also an antiinflammatory cytokine and plays a unique role in the optimal induction and maintenance of IgE production and IgE-mediated allergic responses when IL-4 production is low or absent (DIO, W12). Moreover, IL-13 or IL-4 shows a synergistic effect with TNF-a or IL-5 on eosinophil activation (L20). Recently, IL-11 was found to be involved in the chronic remodeling seen in asthmatic airways and is associated with increasing severity of the disease (Ml6). 

Note Dose cohorts of placebo (not shown) and 20, 50,100, and 200 units of biopharmaceutical X, a putative TLR ligand and immunomodulator, dosed in healthy volunteers. Elevations of C-reactive protein and neopterin 48 hrs after dosing correlate with exposure and with dose emergent AEs. These nonspecific biomarkers appear more sensitive than symptoms or fever to detect biologic activity or reactogenicity. 

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