Antimicrobial concentration-dependent activity

The successful isolation of primary cells is dependent on several factors, some of which are not subject to optimization, such as species, type of tissue, age and sex of donor, and presence of genetic modifications (e.g., knockout animals). Other factors such as the dissociation medium, enzymes and concentrations, temperature, and incubation times can be optimized to ensure the quality and consistency of a primary or cell line preparation. The identification and availability of key growth factors is an important determinant of which primary cells can be maintained in culture. For example lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently it has been shown that lactoferrin at physiological concentrations can also promote bone growth, potently stimulating the proliferation and differentiation of primary osteoblasts (Naot, 2005). 

The degree of ionization of acidic and basic antimicrobial agents depends on pH. Some compounds are active only in the unionized state (e.g., phenolics) whereas others are preferentially active as either the anion or cation. It therefore follows that the activity of a particular concentration of an agent will be enhanced at a pH that favors the formation of the active species. Thus, cationic antibacterials such as acridines and quaternary ammonium compounds are more active under alkaline conditions. Conversely, phenols and benzoic acid are more active in an acid medium. Chlorbutol is less active above pH 5 and unstable above pH 6. Phenylmercuric nitrate is only active at above pH 6 whereas thiomersal is more active under acid conditions. The sporicidal activity of glutaraldehyde is considerably enhanced under alkaline conditions whereas hypochlorites are virtually ineffective at above pH 8. 

The dissociated form Ac- can react with cations, whereas the undissociated form HAc may be active as an antimicrobial agent. The activities of each depend not only on the overall concentration but also on the dissociation constant (which depends on temperature), the pH, the presence and concentration of various cations, etc. It may be argued in these cases not that the activity coefficient is (much) smaller than unity but that we should take the concentration of the species involved in the reaction only. The result is, of course, the same, and we may speak of an apparent activity coefficient. 

Ethanol and aqueous extracts of B. crassifolia bark have also been reported to have good anti-inflammatory activity in the HET-CAM and the cyclooxygenase inhibition assays as well as antimicrobial activity [86, 87, 88]. In addition, we reported that the leaf and bark extracts of B. crassifolia displayed concentration-dependent, spasmogenic effects on rat... 

The PD of antimicrobial dmgs against microorganisms comprises three main aspects spectmm of activity, bactericidal and bacteriostatic activity, and the type of killing action (i.e., concentration-dependent, time-dependent, or co-dependent). Each of these is discussed below. Also described are the PD indices—minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)—and the mechanisms of action of antimicrobial drugs. 

They exist naturally in Swedish type cheeses at a percentage of 1%, derived from Propionibacterium that are involved in ripening of these cheeses. Besides the mould inhibition in cheeses, they can be used as preservatives in baked products, where they cause inhibition of fungi as well as some bacterial species. Moreover, they could be used as antimicrobial factors at levels between 0.1% and 0.38%. Their antimicrobial action depends on the type of microbe and the product pH (highest activity at pH = 6.0). Propionic acid and its salts can be categorized as GRAS when used in concentrations that do not surpass the normal amount required for the accomplishment of the desired effect. 

Figure 1.1. Opposite) Sulpha drugs and their mode of action. The first sulpha drug to be used medically was the red dye prontosil rubrum (a). In the early 1930s, experiments illustrated that the administration of this dye to mice infected with haemolytic streptococci prevented the death of the mice. This drug, while effective in vivo, was devoid of in vitro antibacterial activity. It was first used clinically in 1935 under the name Streptozon. It was subsequently shown that prontosil rubrum was enzymatically reduced by the liver, forming sulphanilamide, the actual active antimicrobial agent (b). Sulphanilamide induces its effect by acting as an anti-metabolite with respect to /iflra-aminobenzoic acid (PABA) (c). PABA is an essential component of tetrahydrofolic acid (THF) (d). THF serves as an essential co-factor for several cellular enzymes. Sulphanilamide (at sufficiently high concentrations) inhibits manufacture of THF by competing with PABA. This effectively inhibits essential THF-dependent enzyme reactions within the cell. Unlike humans, who can derive folates from their diets, most bacteria must synthesize it de novo, as they cannot absorb it intact from their surroundings...

Parabens are approved for use in oral solution and suspensions at a concentration of 0.015% to 0.2% w/v. Due to their low solubility, the sodium salts of parabens are often used in aqueous formulations. The parabens are most effective in the pH range of 2 to 6, and their antimicrobial activity decreases with increasing pH. Additionally, they are very unstable at pH 8 or above in solution. Methyl paraben has also demonstrated incompatibility with sorbitol and may show some discoloration in the presence of iron. The absorption of methylparaben by plastics has been reported with the amount absorbed being dependent upon the type of plastic and vehicle. However, no absorption has been reported for low density polyethylene (LDPE) or high density polyethylene (HDPE) containers. Certain coloring agents such as yellow iron oxide, ultramarine blue, and aluminum silicate can extensively absorb ethyl paraben in simple aqueous systems, thus reducing its preservative efficacy. 

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