Other Agents

PENTOXIFYLLINE Pentoxifylline, a methylxanthine derivative, inhibits cytokine activation of neutrophils and the production of TNF by endotoxin-exposed monocytes. This prevents the adherence of neutrophils to endothelium and the release of toxic degranulation products. The mechanism of this action is believed to be via increasing cyclic adenosine monophosphate concentrations. Animal experiments suggest that treatment with pentoxifylline decreases mortality rate and prevents lung injury by inhibiting migration of neutrophils through the pulmonary capillary endothelium. Also, better survival rates and lower meningeal inflammation have been observed in animals with experimental bacterial meningitis. In healthy human volunteers, pentoxifylline inhibits the rise in TNF induced by endotoxin.

CYCLOOXYGENASE INHIBITORS Two principal pathways of arachidonic acid metabolism exist. The lipoxygenase pathway leads to the production of leukotrienes. Leukotrienes are potent leukocyte chemoattractants. The cyclooxygenase pathway results in the release of thromboxanes and prostaglandins that are important regulators of vascular tone.

Ibuprofen is a cyclooxygenase inhibitor. In animal models of endotoxin shock and shock from peritoneal implantation or intravenous infusion of bacteria, ibuprofen decreases mortality, reverses hemodynamic, metabolic, and blood coagulation abnormalities, improves pulmonary gas exchange, and attenuates the development of increase in microvascular permeability. These results are seen with ibuprofen when administered before and after the septic insult. In preliminary human studies, treatment with ibuprofen attenuates flu-like symptoms and reduces fever, tachycardia, and metabolic rate in volunteers exposed to endotoxin. Recently, the Ibuprofen Sepsis Study Group published its findings of a randomized, double-blind, placebo-controlled trial of intravenous ibuprofen (10 mg/kg per body weight given every 6 h for a total of 8 doses) in 455 patients who had sepsis. It found that the ibuprofen-treated group had significant declines in temperature, heart rate, oxygen consumption, lactic acidosis, and urinary levels of prostacyclin and thromboxane. However, ibuprofen did not reduce the incidence or duration of shock or ARDS, and did not significantly improve the rate of survival at 30 days (mortality, 37 percent with ibuprofen versus 40 percent with placebo). No increase in adverse events (renal dysfunction, gastrointestinal bleeding) was noted in the ibuprofen group. No definitive conclusions can be made from any of the studies regarding the efficacy of ibuprofen in sepsis. However, both human and animal studies to date have suggested that ibuprofen results in decreased metabolic demand on patients with sepsis.

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How To Reduce Acne Scarring

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Acne is a name that is famous in its own right, but for all of the wrong reasons. Most teenagers know, and dread, the very word, as it so prevalently wrecks havoc on their faces throughout their adolescent years.

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