Given a passage, 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.

Q: Doxorubicin is a cytotoxic drug with potential for severe myelosuppression that is highly variable and poorly predictable.', 'We correlated CBR1 and CBR3 genotypes with the pharmacokinetics and pharmacodynamics of doxorubicin in 101 Southeast Asian breast cancer patients receiving first-line doxorubicin.', 'A common CBR3 11G>A variant was associated with lower doxorubicinol area under the concentration-time curve (AUC)/doxorubicin AUC metabolite ratio (P=0.009, GG vs. AA; trend test, P=0.004), lower CBR3 expression in breast tumor tissue (P=0.001, GG vs. AA), greater tumor reduction (P=0.015, GG vs. AA), and greater percentage reduction of leukocyte and platelet counts at nadir (trend test, P < or = 0.03). Chinese and Malays had higher frequency of the CBR3 11G>A variant than Indians (P < or = 0.002). Another variant CBR3 730G>A was associated with higher doxorubicinol AUC (P=0.009, GG vs. AA) and CBR3 expression in breast tumor tissue (P=0.001, GG vs AA).

A: Does genotype of human carbonyl reductase CBR3 correlate with doxorubicin disposition and toxicity?
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Q: Autonomic dysfunction has previously been described in primary biliary cirrhosis patients. In nonhepatic diseases, fatigue is associated with autonomic dysfunction and impaired baroreflex sensitivity. Here, we investigate the prevalence of autonomic dysfunction using highly sensitive detection modalities and its relationship with fatigue in both noncirrhotic and cirrhotic primary biliary cirrhosis patients.', 'Autonomic reflex tests were performed, using continuous blood pressure and electrocardiograph measurement in 47 primary biliary cirrhosis patients and age and sex-matched controls. Fatigue was measured using the primary biliary cirrhosis-40.', 'In all, 100% of precirrhotic and 81% of cirrhotic primary biliary cirrhosis patients exhibited autonomic dysfunction. Valsalva ratio and 30 : 15 ratio (measures of parasympathetic autonomic dysfunction) were significantly lower in primary biliary cirrhosis patients than in controls (valsalva ratio: 1.42 vs. 1.57; P=0.01, 30 : 15: 1.1 vs. 1.2; P=0.01). Blood pressure drop on standing (sympathetic autonomic dysfunction) was greater in the primary biliary cirrhosis group (31+/-22 vs. 23+/-15 mmHg; P=0.03). Valsalva phase IV size was similar between primary biliary cirrhosis patients and controls, however, time to phase IV was significantly longer (P=0.01), suggesting adrenergic failure. Increasing fatigue was associated with impaired baroreflex sensitivity and an earlier, bigger phase IV (sympathetic overactivity). No significant differences were seen, between cirrhotic and noncirrhotic patients.

A: Does autonomic dysfunction in primary biliary cirrhosis correlate with fatigue severity?
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Q: Aminoguanidine (AG), a well known inhibitor of advanced glycation end products, has been reported to attenuate cardiac hypertrophy and fibrosis. However, the underlying mechanism by which AG exerts its anti-fibrotic activity is not well understood. Reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) are implicated as playing a major role in the development of cardiac fibrosis. Hence, the present study was designed to investigate the effect of AG on ROS generation and MMPs during the progress of hypertrophic growth.', 'Isoproterenol (ISO) (7 mg/kg/day, s.c., for 15 days) was used to induce cardiac hypertrophy in experimental adult Wistar rats. ISO-treated rats were co-treated with AG (50 mg/kg/day, i.p., for 15 days). Ventricular collagen deposition, gelatinase activity of MMP-2 and MMP-9, and the level of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were investigated. In addition, in silico docking of MMP-2 and MMP-9 proteins, ROS generation, and nuclear translocation of NF-κB-p65 were also studied.', 'AG co-treatment markedly attenuated the ISO-induced hypertrophic growth and fibrosis. Heart-weight-to-body weight ratio and ventricular collagen levels were normalized upon AG co-treatment. A significantly decreased level of ventricular ROS generation (p < 0.001) and NF-κB-p65 nuclear translocation was observed in the rat hearts co-treated with AG. Furthermore, in silico docking analysis revealed that AG interacts at the active site of MMP-2 and MMP-9.

A:
Does aminoguanidine inhibit ventricular fibrosis and remodeling process in isoproterenol-induced hypertrophied rat hearts by suppressing ROS and MMPs?
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