ABSTRACT
<p><b>BACKGROUND</b>Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.</p><p><b>METHODS</b>The mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.</p><p><b>RESULTS</b>The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).</p><p><b>CONCLUSIONS</b>DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Dopamine Agonists , Therapeutic Uses , Leukocytes, Mononuclear , Metabolism , Nuclear Receptor Subfamily 4, Group A, Member 2 , Genetics , Parkinson Disease , Drug Therapy , Genetics , RNA, Messenger , GeneticsABSTRACT
After oral administration of Salvia miltiorrhiza (Danshen in Chinese), Panax notoginseng (Sanqi in Chinese) and Danshen Sanqi combination suspensions to Beagle dogs, the plasma concentration-time profiles of danshensu, tanshinone II(A), cryptotanshinone, notoginsenoside R1, ginsenoside Rg1 and Rb1 were analyzed by LC-MS/MS. Pharmacokinetic parameters were calculated and analyzed with BAPP 2.0 software. The results showed that the Cmax and AUC of danshensu, notoginsenoside R1, ginsenoside Rg1 and Rb1 in Danshen Sanqi combination group all decreased in comparison with those of Danshen or Sanqi given alone, while the CLz/F and Vz/F increased to some extent. No significant differences of the pharmacokinetics of tanshinone II(A) and cryptotanshinone were observed between groups.
Subject(s)
Animals , Dogs , Female , Male , Administration, Oral , Area Under Curve , Abietanes , Blood , Pharmacokinetics , Drug Combinations , Drugs, Chinese Herbal , Pharmacokinetics , Ginsenosides , Blood , Pharmacokinetics , Lactates , Blood , Pharmacokinetics , Panax notoginseng , Chemistry , Phenanthrenes , Blood , Pharmacokinetics , Plants, Medicinal , Chemistry , Salvia miltiorrhiza , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To summarize the experience with orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>A retrospective analysis of 105 cases of liver transplantation in our hospital was carried out.</p><p><b>RESULTS</b>All the 105 OLT operations were performed successfully and the operation time ranged from 210-350 min (mean 250 min), with anhepatic phase ranging from 35-65 min (mean 53.5 min) and blood transfusion during operation ranging from 0-6600 ml (mean 400 ml). Ninety-five patients recovered smoothly while the rest 10 died, with the success rate of OLT of 90.5%. Postoperative complications included biliary tract complication (12 cases, 11.4%) and abdominal bleeding (6 cases).</p><p><b>CONCLUSIONS</b>Reducing hemorrhage during operation is the most important factor to ensure successful OLT. Thorough hemostasis during operation and sufficient blood supply to the bile duct can significantly reduce postoperative bile duct complications.</p>