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document
Norfloxacin modulates the inflammatory response and directly affects neutrophils in patients with decompensated cirrhosis . BACKGROUND & AIMS Patients with cirrhosis undergoing selective intestinal decontamination with norfloxacin show a reduction in serum cytokine levels , probably because of a combined effect of norfloxacin on bowel flora and neutrophils . METHODS Thirty-one patients with cirrhosis receiving norfloxacin ( 400 mg/day ) were included . Blood samples were collected at 0.5-4 hours ( peak samples group , n = 47 ) and at 22-24 hours ( trough samples group , n = 84 ) after dose . Fifty-nine ascitic fluid samples were obtained . Single doses of norfloxacin and trimethoprim/sulfamethoxazole were administered to 13 and 5 patients , respectively , ( temporal profile group ) and samples were collected at 0 , 0.5 , 1 , 1.5 , 2 , 4 , and 24 hours . Norfloxacin , trimethoprim/sulfamethoxazole , cytokines , nitric oxide , expression levels of nuclear factor ( NF ) -kappaB and inhibitor of NF-kappaB ( IkB-alpha ) , neutrophil oxidative burst , and rate of apoptotic events were determined . RESULTS All samples were bacterial DNA negative and had no significant levels of lipopolysaccharide . Serum and ascitic levels of tumor necrosis factor-alpha , interferon-gamma , interleukin-12 , and nitric oxide were significantly lower in peak than in trough samples . A correlation was present between serum norfloxacins concentrations and tumor necrosis factor-alpha ( r = -0.68 ; P < .001 ) , interferon-gamma ( r = -0.66 ; P < .001 ) , interleukin-12 ( r = -0.66 ; P < .001 ) , and nitric oxide ( r = -0.68 ; P < .001 ) . Serum norfloxacin 's highest concentrations ( 1 +/- 0.5 microg/mL ) were achieved at 1-2 hours and concurred in time with the lower levels of cytokines and nitric oxide . Intracellular norfloxacin 's highest levels ( 2 +/- 1 microg/mL/10 ( 7 ) cells ) were observed at 2 hours and concurred with a lower NF-kappaB expression , a reduced anion superoxide generation , and apoptotic rate in response to phorbol myristate acetate . Trimethoprim/sulfamethoxazole did not significantly modulate cytokine expression . CONCLUSIONS Norfloxacin but not trimethoprim/sulfamethoxazole modulates inflammatory response and directly affects neutrophils in patients with cirrhosis .
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Intervention_Pharmacological
Norfloxacin
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Intervention_Pharmacological
norfloxacin
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Intervention_Pharmacological
norfloxacin
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Intervention_Pharmacological
norfloxacin
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Intervention_Pharmacological
norfloxacin
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Intervention_Pharmacological
trimethoprim/sulfamethoxazole
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Intervention_Pharmacological
Norfloxacin
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Intervention_Pharmacological
trimethoprim/sulfamethoxazole
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Intervention_Pharmacological
cytokines
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Intervention_Pharmacological
nitric oxide
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Intervention_Pharmacological
norfloxacins
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Intervention_Pharmacological
interferon-gamma
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Intervention_Pharmacological
nitric oxide
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Intervention_Pharmacological
Trimethoprim/sulfamethoxazole
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Intervention_Pharmacological
Norfloxacin
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Intervention_Pharmacological
trimethoprim/sulfamethoxazole
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Outcome_Physical
Serum and ascitic levels of tumor necrosis factor-alpha , interferon-gamma
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Outcome_Physical
interleukin-12
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Outcome_Physical
nitric oxide
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Outcome_Physical
serum norfloxacins concentrations and tumor necrosis factor-alpha
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Outcome_Physical
interferon-gamma
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Outcome_Physical
interleukin-12
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Outcome_Physical
nitric oxide
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Outcome_Physical
Serum norfloxacin 's highest concentrations
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Outcome_Physical
cytokines and nitric oxide
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Outcome_Physical
Intracellular norfloxacin 's highest levels
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Outcome_Physical
cytokine expression
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Participant_Condition
decompensated cirrhosis
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Participant_Condition
cirrhosis
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Participant_Sample-size
Thirty-one
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Participant_Condition
cirrhosis
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Participant_Condition
cirrhosis