MELD exceptions for portopulmonary hypertension: current policy and future implementation.

Since 2006, waitlist candidates with portopulmonary hypertension (POPH) have been eligible for standardized Model for End-Stage Liver Disease (MELD) exception points. However, there are no data evaluating the current POPH exception policy and its implementation. We used Organ Procurement and Transplantation Network (OPTN) data to compare outcomes of patients with approved POPH MELD exceptions from 2006 to 2012 to all nonexception waitlist candidates during this period. Since 2006, 155 waitlist candidates had approved POPH MELD exceptions, with only 73 (47.1%) meeting the formal OPTN exception criteria. Furthermore, over one-third of those with approved POPH exceptions either did not fulfill hemodynamic criteria consistent with POPH or had missing data, with 80% of such patients receiving a transplant based on receiving exception points. In multivariable multistate survival models, waitlist candidates with POPH MELD exceptions had an increased risk of death compared to nonexception waitlist candidates, regardless of whether they did (hazard ratio [HR]: 2.46, 95% confidence interval [CI]: 1.73-3.52; n = 100) or did not (HR: 1.60, 95% CI: 1.04-2.47; n = 55) have hemodynamic criteria consistent with POPH. These data highlight the need for OPTN/UNOS to reconsider not only the policy for POPH MELD exceptions, but also the process by which such points are awarded.

Role of reactive oxygen species in expulsion of Nippostrongylus brasiliensis from rats.

To understand the mechanism for the expulsion of Nippostrongylus brasiliensis from rats, age-dependent variations in the metabolism of reactive oxygen species in the parasite and the host intestines were examined. N. brasiliensis showed an age-dependent increase in its susceptibility to xanthine-xanthine oxidase and t-butyl hydroperoxide generated oxidants as well as to H2O2. Protection obtained with several scavengers suggested that the worms were damaged by the combined action of oxidants generated by the in vitro systems employed. The level of superoxide dismutase in the nematode and its release into the surroundings exhibited a marked depression with advancement of age. No such alteration was, however, recorded for catalase and glutathione peroxidase. An appreciable decrease in the level of reduced glutathione in older N. brasiliensis appears to render them prone to oxidant attack. The rat intestines, on the other hand, exhibited an appreciable depression in catalase and a reduced glutathione content with progress of the infection. Vitamin E levels were elevated. The release of O2-. and H2O2 by the intestines was also found to be greater during later stages of the infection. The combined effect of the changes observed in N. brasiliensis and in the rat intestines may be at least partly responsible for expulsion of the nematode from the rats after day 10.

Effect of anthelmintics on the antioxidant system of Nippostrongylus brasiliensis.

To understand the mode of anthelmintic action of thiabendazole and methyl-[5-[[4-(2-pyridinyl)-l-piperazinyl]carbonyl]-1H-benzimidazole- 2-yl] carbamate (C.D.R.I. compound 81/470) against Nippostrongylus brasiliensis, their effect on the metabolism of reactive oxygen species in the parasite as well as in rat intestine was examined. Both drugs produced a significant depression in the levels of superoxide dismutase (SOD) and reduced glutathione (GSH) of the parasite. Release of antioxidant enzymes by the drug-treated worms was also found to be appreciably lowered. Both thiabendazole and compound 81/470 induced a depression in the levels of all five constituents of the antioxidant system of rat intestine but significant alterations were detected only in the GSH content of infected and the SOD activity of normal intestine. The production of O2- by treated intestine was, on the other hand, markedly enhanced. Increased formation of O2- by the host intestine accompanied with the reduced level of SOD and GSH in N. brasiliensis appear to have a deleterious effect on the parasite. Consequently, the drug-treated worms are unable to retain themselves in situ and are ultimately expelled. The greater effect produced on these parameters by thiabendazole compared to compound 81/470 is consistent with the relative efficacy of these anthelmintics.

Reactive oxygen intermediates metabolizing enzymes in Ancylostoma ceylanicum and Nippostrongylus brasiliensis.

Adult worms of Ancylostoma ceylanicum and Nippostronglyus brasiliensis were found to possess an active system for the detoxification of reactive oxygen intermediates. Xanthine oxidase, which is known to produce superoxide anion, was detected in both the nematode parasites in significant activities. Superoxide anion, thus produced, may quickly be eliminated by superoxide dismutase. Both parasites also exhibited the presence of catalase, peroxidase, and glutathione peroxidase for efficient removal of hydrogen peroxide. Glutathione reductase and glucose-6-phosphate dehydrogenase were, however, detected in low levels of activities. Endowment of A. ceylanicum and N. brasiliensis with these antioxidant enzymes, therefore, enables them to evade the host's effector mechanism for their survival. Superoxide dismutase of both these nematodes showed marked inhibition by KCN and, hence, the enzyme appears to be of copper-zinc type.