TASK DEFINITION: In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
PROBLEM: Context: Vitamin A plays a major role in lipid metabolism. Previously, we reported that chronic vitamin A feeding (129 mg/kg) for two months normalized the abnormally high plasma HDL-cholesterol (HDL-C) levels in hypercholesterolemic obese rats by upregulating the hepatic scavenger receptor class B type 1 (SR-BI) expression. In this report, we hypothesize that the administration of a dose less than 129 mg of vitamin A/kg would also be effective in lowering the plasma HDL-C levels in these rats.', 'Changes in the activity and expression of proteins related to RCT were analyzed together with blood parameters in five-month-old male lean and obese rats supplemented with 2.6 (control group), 26, 52 and 129 mg of vitamin A/kg as retinyl palmitate for 20 weeks.', 'Vitamin A supplementation in the obese rats decreased the plasma HDL-C levels with a concomitant increase in the hepatic SR-BI expression and lipase activity compared to that observed in the control diet-fed obese rats treated with 2.6 mg of vitamin A/kg diet. Furthermore, vitamin A supplementation at doses of 52 and 129 mg/kg diet reduced the plasma lecithin cholesterol acyltransferase activity and increased the hepatic ATP-binding cassette transporter protein A1 expression in the obese rats. Interestingly, most of these changes were not observed in the lean rats fed a vitamin A-enriched diet.\Question: Does vitamin A-enriched diet modulate reverse cholesterol transport in hypercholesterolemic obese rats of the WNIN/Ob strain?

SOLUTION: Chronic feeding of a vitamin A-enriched diet in hypercholesterolemic obese rats normalizes the plasma HDL-C level and presumably improves RCT, with an effective dose of 52 mg/kg diet. Further studies should focus on the pharmacological potential of vitamin A supplementation to correct an abnormal human obesity-associated lipoprotein metabolism.

PROBLEM: Context: Progress in the management of patients with medically intractable epilepsy is impeded because we do not fully understand why pharmacoresistance happens and how it can be predicted. The presence of multiple seizures prior to medical treatment has been suggested as a potential predictor of poor outcome. In the present study, we used an animal model of temporal lobe epilepsy to investigate whether pharmacoresistant rats differ in seizure frequency from pharmacoresponsive animals.', 'Epilepsy with spontaneous recurrent seizures (SRS) was induced by status epilepticus. Frequency of SRS was determined by video/EEG (electroencephalography) monitoring in a total of 33 epileptic rats before onset of treatment with phenobarbital (PB).', 'Thirteen (39%) rats did not respond to treatment with PB. Before treatment with PB, average seizure frequency in PB nonresponders was significantly higher than seizure frequency in responders, which, however, was due to six nonresponders that exhibited > 3 seizures per day. Such high seizure frequency was not observed in responders, demonstrating that high seizure frequency predicts pharmacoresistance in this model, but does not occur in all nonresponders.\Question: Is high seizure frequency prior to antiepileptic treatment a predictor of pharmacoresistant epilepsy in a rat model of temporal lobe epilepsy?

SOLUTION: The data from this study are in line with clinical experience that the frequency of seizures in the early phase of epilepsy is a dominant risk factor that predicts refractoriness. However, resistance to treatment also occurred in rats that did not differ in seizure frequency from responders, indicating that disease severity alone is not sufficient to explain antiepileptic drug (AED) resistance. These data provide further evidence that epilepsy models are useful in the search for predictors and mechanisms of pharmacoresistance.

PROBLEM: Context: To compare single- and multiple-dose maraviroc exposures in cervicovaginal fluid (CVF) and vaginal tissue (VT) with blood plasma (BP) and quantify maraviroc protein binding in CVF.', 'Open-label pharmacokinetic study.', 'In 12 HIV-negative women, 7 paired CVF and BP samples were collected over 12 hours after 1 maraviroc dose. Subjects then received maraviroc twice daily for 7 days. After the last dose, subjects underwent CVF and BP sampling as on day 1, with additional sampling during terminal elimination. VT biopsies were obtained at steady state.', 'Day 1 and day 7 median maraviroc CVF AUCtau were 1.9- and 2.7-fold higher, respectively, than BP. On day 1, 6 of 12 subjects had detectable maraviroc CVF concentrations within 1 hour; 12 of 12 were detectable within 2 hours, and all exceeded the protein-free IC90. On day 7, maraviroc CVF protein binding was 7.6% and the VT AUCtau was 1.9-fold higher than BP. Maraviroc CVF concentrations 72 hours after dose and BP concentrations 12 hours after dose were similar.\Question: Does maraviroc concentrate in the cervicovaginal fluid and vaginal tissue of HIV-negative women?

SOLUTION:
Higher maraviroc exposure in the female genital tract provides a pharmacologic basis for further evaluation of chemokine receptor 5 antagonists in HIV infection prophylaxis. This is the first study to report antiretroviral VT concentrations, CVF protein binding, and CVF terminal elimination.