Volume 137, Issue 5, Pages 1669-1679.e1 (November 2009) Norfloxacin Modulates the Inflammatory Response and Directly Affects Neutrophils in Patients With Decompensated Cirrhosis  Pedro Zapater, Rocío Caño, Lucía Llanos, Antonio J. Ruiz–Alcaraz, Sonia Pascual, Claudia Barquero, Rocío Moreu, Pablo Bellot, José F. Horga, Carlos Muñoz, Jara Pérez, Pilar García–Peñarrubia, Miguel Pérez–Mateo, José Such, Rubén Francés  Gastroenterology  Volume 137, Issue 5, Pages 1669-1679.e1 (November 2009) DOI: 10.1053/j.gastro.2009.07.058 Copyright © 2009 AGA Institute Terms and Conditions

Figure 1 Relationship between norfloxacin concentrations and cytokine and NOx levels, both in serum (n = 131) and AF (n = 59). TNF-alpha, tumor necrosis factor α; IFN-gamma, interferon-γ; IL-12, interleukin 12; NOx, nitric oxide metabolites; ND, not detected; r, Pearson correlation coefficient. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions

Figure 2 Norfloxacin and TNF-α concentrations in 6 patients with a total of 9 consecutive serum samples collected during follow-up. Sample 1 refers to the sample collected at inclusion. Subsequent samples were collected at 15 days and 1, 2, 4, 7, 8, 9, and 10 months, respectively, after inclusion. TNF-alpha, tumor necrosis factor-α. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions

Figure 3 Temporal pattern of intracellular norfloxacin concentrations (A), serum cytokines (B), and NOx levels (C) according to serum norfloxacin concentrations (n = 8). Data are expressed as mean ± SD (bars). Each time point value was compared with its corresponding value at 0 hours and to the previous time point value. X-axis is lineal from 0 to 2 hours. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions

Figure 4 Temporal relationship between intracellular levels of norfloxacin and NF-κB and IkBα. Data are expressed as mean ± SD. Cell samples were sequentially obtained from 8 norfloxacin-naïve patients before and after the administration of 400 mg of oral norfloxacin. For all variables, each time point value was compared with its corresponding value at 0 hours and at 0.5 hours. X-axis is lineal from 0 to 2 hours. AU, arbitrary units. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions

Figure 5 Temporal relationship between intracellular generation of anion superoxide, as determined by yellow nitroblue tetrazolium (Y-NBT) (A) and intracellular annexin V (B) with the intracellular levels of norfloxacin in resting cells and PMA-stimulated cells. Data are expressed as mean ± SD. Blood cell samples were obtained from 8 norfloxacin-naïve patients before and after the administration of 400 mg of oral norfloxacin. For all variables, each time point value was compared with its corresponding value at 0 hours and at 0.5 hours. X-axis is lineal from 0 to 2 hours. PMA, phorbol 12-myristate 13-acetate; OD, optical density. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions

Figure 6 Temporal relationship between intracellular levels of norfloxacin or trimethoprim/sulfamethoxazole and NF-κB. Data are expressed as mean ± SD. Cell samples were sequentially obtained from 5 patients before and after drug administration (see Patients and Methods section). For all variables, each time point value was compared with its corresponding value at 0 hours and at 0.5 hours. X-axis is lineal from 0 to 2 hours. AU, arbitrary units. Gastroenterology 2009 137, 1669-1679.e1DOI: (10.1053/j.gastro.2009.07.058) Copyright © 2009 AGA Institute Terms and Conditions