Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Input: Consider Input: Context: Isotretinoin is effective in the treatment of severe acne and rosacea. Both parent drug and its main metabolite 4-oxo-isotretinoin are potentially teratogenic compounds and contain a carboxylic acid moiety. In the presence of ethanol, naturally occurring as well as synthetic retinoids also containing a carboxylic acid moiety are capable of undergoing an ethyl esterification with the metabolic formation of more lipophilic compounds with a much longer terminal half-life.', 'To determine if isotretinoin (13-cis-RA), its main metabolite 4-oxo-isotretinoin (4-oxo-13-cis-RA), and other possible metabolites in the presence or absence of ethanol are converted to their corresponding ethyl derivatives in patients with severe acne or rosacea after multiple isotretinoin dosing. In addition, pharmacokinetic parameters of the parent drug and its 4-oxo metabolite were determined.', 'Eleven patients with severe acne or rosacea were treated with isotretinoin daily for 3 months and investigated pharmacokinetically during 24 h after 1 month of treatment and for up to 28 days after discontinuation of therapy. A possible influence of ethanol was evaluated using a simple self-administered questionnaire and by measuring serum ethanol levels during treatment. The concentrations of isotretinoin, 4-oxo-isotretinoin and possible ethylated and nonethylated metabolites were measured by reverse-phase high-performance liquid chromatography.', "Although seven of 11 patients had a considerable weekly alcohol intake, no endogenous synthesis of ethyl derivatives of isotretinoin, the main 4-oxo metabolite or the all-trans compounds was chromatographically detectable in any of the patients' plasma samples during the treatment period. Multiple dose pharmacokinetic data for the parent drug and its main metabolite were comparable to previous studies.
Answer: The metabolism and pharmacokinetics of isotretinoin and its main metabolites are not influenced by ethanol during long-term isotretinoin treatment. After ceasing long-term isotretinoin therapy the recommended period of 1 month for using anticonceptive measures in fertile women seems adequate.

Output: Are the metabolism and pharmacokinetics of isotretinoin in patients with acne and rosacea influenced by ethanol?


Input: Consider Input: Context: Despite recent advances in preoperative diagnostic imaging and operative techniques, biliary variation of the donor still remains a challenge in the procurement of graft. The supraportal right bile duct (BD) variant including presentation as trifurcation is a potential trap for injuring the remnant bile duct of donor.', 'Before living/related-donor liver transplantation (LRLT), cholangiogram with magnetic resonance images of each donor was performed as a routine. After exploration of the donor before hilar dissection, intraoperative chloangiography (IOC) was routinely performed. Among the supraportal right bile duct variants, if the preoperative cholangiography showed a suspected trifurcation of the bile duct, we then performed 3 sessions of IOC during liver graft procurement, including prior to hilar dissection, before the division of bile ducts and after the division. We reviewed the cholangiogram and the postoperative laboratory data of a consecutive series of 25 donors of LRLT.', 'There was no division injury of the remnant bile duct of all of the donors.
Answer: Repeated IOC is suggested as a routine for variants of supraportal right bile ducts especially trifurcation pattern in graft procurement to avoid the injury of donor remnant bile ducts.

Output: Is repeated introperative cholangiography helpful for donor safety in the procurement of right liver graft with supraportal right bile duct variants in living-donor liver transplantation?


Input: Consider Input: Context: Nucleoside analogues are suspected of playing a role in peripheral fat loss in patients during long-term treatment with antiretroviral drugs.', 'We compared the long-term effects of stavudine (10 microM), zidovudine (1 muM), didanosine (10 microM), abacavir (4 microM), lamivudine (10 microM), and tenofovir (1 microM), near their maximum concentration values, on the differentiation, lipid accumulation, survival and mitochondrial function of differentiating 3T3-F442A and differentiated 3T3-L1 adipocytes.', 'None of the nucleoside reverse transcriptase inhibitors (NRTI) markedly altered the differentiation of 3T3-F442A cells, as shown by the unmodified percentage of cells with lipid droplets on day 7 and the expression of the early differentiation markers CCAAT/enhancer binding protein (C/EBP) beta (on day 2) and sterol regulatory element-binding protein. However, stavudine and zidovudine altered the lipid phenotype, decreasing the lipid content and expression of markers involved in lipid metabolism, namely C/EBPalpha, peroxisome proliferator-activated receptor gamma, adipocyte lipid binding protein 2, fatty acid synthase and acetyl-coenzyme A carboxylase. Stavudine and zidovudine, contrary to the other NRTI, drove 5-10% of 3T3-F442A cells towards apoptosis, and reduced the lipid content and survival of differentiated 3T3-L1 adipocytes. Stavudine and zidovudine increased mitochondrial mass by two to fourfold, and lowered the mitochondrial membrane potential (JC-1 stain) as did zalcitabine (0.2 microM). Co-treatment with zidovudine plus lamivudine, or zidovudine plus lamivudine and abacavir, did not increase the effect of zidovudine on cell viability or apoptosis.
Answer: The thymidine analogues stavudine and zidovudine decreased lipid content, mitochondrial activity, and adipocyte survival in vitro.


Output: Do the HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine alter adipocyte functions in vitro?