Infection models

Burke DH, Scales L, Andrews K, Gold L (1996) Bent pseudoknots and novel RNA inhibitors of type 1 human immunodeficiency virus (HlV-1) reverse transcriptase. J Mol Biol 264 650-666 Burrer R, Neuman BW, Ting JP, Stein DA, Moulton HM, Iversen PL, Kuhn P, Buchmeier MJ (2007) Antiviral effects of antisense morphoUno oligomers in murine coronavirus infection models, J Virol 81 5637-5648... 

In response to danger signals, a significant number of both mDC and pDC precursors appear de novo into the circulation (5,13). However, their migration pathways are flexible and are largely dependent on tissue microenvironments. In a cutaneous herpes simplex virus (HSV)-l infection model, newly appeared... 

Fig. 3. DC network dictates peripheral tolerance and immunity. The type and activation of DCs recruited to effector lymph nodes determine the efficacy of immune responses, (a) Steady-state migration, (b) Skin infection model, (c) Liver inflammation model.

Fig. 4. Regulation by chemokines of recruited DC-mediated immune responses, (a) The effect of CCL21 on mDC migration in liver disease model, (b) The effect of CXCL9 on pDC migration in skin infection model.

An interesting imaging probe Id that can selectively target bacteria was recently reported by Smith et al. [31] also based on a heptamethine chromophore. The probe is composed of a bacterial affinity group, which is a synthetic zinc (II) coordination complex that targets the anionic surfaces of bacterial cells and a near infrared dye. The probe allowed detection of Staphylococcus aureus in a mouse leg infection model using whole animal near-infrared fluorescence imaging. 

Thiolactomycin (16) is another natural product that reversibly inhibits E. coli FabF, FabB, and FabH with respective ICso s of 6, 25 and 110 (iM. Unlike cerulenin, it binds the malonyl-ACP site of the enzyme [27]. Despite modest double-digit MICs on . coli, S. aureus, Serratia marces-cens, and Mycobacterium tuberculosis, 16 has generated quite some interest due to its good in vivo protection against an oral or intramuscular S. marcescens urinary tract infection model where it displayed rapid tissue distribution [28]. Despite several medicinal chemistry efforts, thiolactomycin has proven difficult to optimize due to some strict functional group requirements for its SAR [29]. 

Compound 21a in combination with ceftazidime or cefpirome at a ratio of 1 1 was observed to have efficacy in vivo [96]. It improved the efficacy of both the cephalosporins in both a murine systemic infection model with cephalosporinase-resistant rods and in urinary tract infection models with cephalosporin-resistant P. aeruginosa. Further developments in this class of compounds would be rewarding. 

Webb MS, Boman NL, Wiseman DJ, et al. Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation. Antimicrob Agents Chemother 1998 42 45. 

De Boer, M.L., Kum, W.W. and Chow, A.W., Staphylococcus aureus isogenic mutant, deficient in toxic shock syndrome toxin-1 but not staphylococcal enterotoxin A production, exhibits attenuated virulence in a tampon-associated vaginal infection model of toxic shock syndrome, Can. J. Microbiol., 45, 250-256,... 

Eisensmith, S.P., and Jones, A.L. 1981. Infection model for timing fungicide applications to control cherry leaf spot. Plant Dis. 65 955-958. 

Mice (see Note 3) several inbred strains of mice have been used in this infection model including BALB/c and CBA/Ca among others (see Note 4). 

Animal models of disease play a critical role in the drug discovery process and are important in the lead candidate selection process as well. Categories of animal disease models include spontaneous disease, induced models (e.g., chemically, immunologically), xenograft models, infection models, and genetically modified models (e.g., transgenic knockouts (KOs) or knock-ins (KIs), humanized animals (e.g., expressing the human protein or receptor). The sub-... 

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