1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (Sal) is a kind of catechol isoquinoline compound, which mainly exists in mammalian brain and performs a variety of biological functions. Through in vivo metabolism, Sal can be transformed into endogenous neurotoxins and can participate the occurrence of Parkinson’s disease (PD). This has attracted widespread concern of researchers. Recently, many research works have shown that Sal may lead to alcohol addiction and regulate hormone release of the neuroendocrine system, which indicated that it is a potential regulator of dopaminergic neurons. In this paper, we discuss the neural functions of Sal on the above aspects, and wish to provide some theoretical supports for further research on its mechanism.
Objective To compare the vasoactive effects of norepinephrine( NE) and dopamine of different doses on isolated rabbit pulmonary and systemic arteries in septic shock. Methods Six paired pulmonary and systemic arterial rings were prepared fromsix rabbits, and matched randomly assigned into a normal group and a LPS group. The assigned groups were intervened by different doses of NE. Another six paired pulmonary and systemic arterial rings were prepared from another six rabbits. They were assigned to different groups as above and intervened by different doses of dopamine. The LPS groups were pre-incubated in RPMI mediumsupplemented with4 μg/mL LPS to simulate septic shock. The tension of arterial rings was measured and its response to NE and dopamine were studied. Results ( 1) In the normal groups, the contraction of the systemic arteries was ber than the pulmonary arteries in response to low,middle dose of NE, and high dose of dopamine ( all P lt; 0. 05) , and which was weaker in response to middle dose of dopamine and similar in response to high dose of NE( P gt;0. 05) . Both the pulmonary and systemic arteriesrelaxed in response to low dose of dopamine. ( 2) After LPS pre-incubation, the contraction of the systemic arteries was weaker than the pulmonary arteries in response to low dose of dopamine ( P lt;0. 05) , and which was similar in response to low,middle and high dose of NE, and middle, high dose of dopamine. ( 3) Comparing the LPS groups with the normal groups, the contraction in response to middle dose of dopamine increased in the systemic arteries and dreased in the pulmonary arteries ( P lt;0. 05) . Conclusions In septic shock, the vasoactive effect of different doses of NE is not different between pulmonary and systemic arteries. But middle dose of dopamine can increase the contraction of systemic arteries and decrease the contraction of pulmonary arteries.
Objective To systemically review the efficacy and safety of dopamine versus norepinephrine in patients with septic shock. Methods Database searches of MEDLINE, EMbase, Cochrane Controlled Trials Register, VIP, CNKI, and CBM (from the date of database establishment to June 2011) were conducted. Additional studies for collecting relevant data were retrieved via both references of articles and direct contact with authors. Prospectively, randomized controlled trials (RCTs) of dopamine compared with norepinephrine therapy in septic shock patients were selected. The quality of included trials was assessed and relevant data were extracted. Then statistical analysis was performed using RevMan 5.1. Results Nine trials with 3 179 participants were included. The results of meta-analysis showed: compared with norepinephrine, dopamine was associated with a significant 12% elevation in the risk ratio of in-hospital death events of septic shock patients (RR=1.12, 95%CI 1.04 to 1.21, P=0.002). The risk of arrhythmias in dopamine group was 2.63-fold than that in norepinephrine group (RR=2.63, 95%CI 1.51 to 4.55, P=0.000 6). The cardiac index of septic patients in dopamine group was higher than that in norepinephrine group (MD=0.42, 95%CI 0.21 to 0.63, Plt;0.000 1). No significant difference could be found in the heart rate (MD=17.05, 95%CI –0.71 to 34.81, P=0.06) and mean arterial pressure (MD= –0.87, 95%CI –24.97 to 7.62, P=0.30). Conclusion Findings from this meta-analysis suggest that compared with dopamine, norepinephrine significantly reduces both 28-day mortality of septic shock patients and incidence rate of arrhythmias. Norepinephrine is better than dopamine in aspects of efficacy and safety.
Objective To develop a drug-loaded composite microsphere that can simultaneously release the berberine (BBR) and naringin (NG) to repair infectious bone defects. MethodsThe NG was loaded on mesoporous microspheres (MBG) to obtain the drug-loaded microspheres (NG-MBG). Then the dual drug-loaded compound microspheres (NG-MBG@PDA-BBR) were obtained by wrapping NG-MBG with polydopamine (PDA) and modifying the coated PDA with BBR. The composite microspheres were characterized by scanning electron microscopy, X-ray diffraction, specific surface area and pore volume analyzer, and Fourier transform infrared spectroscopy; the drug loading rate and release of NG and BBR were measured; the colony number was counted and the bacterial inhibition rate was calculated after co-culture with Staphylococcus aureus and Escherichia coli for 12 hours to observe the antibacterial effect; the biocompatibility was evaluated by live/dead cell fluorescence staining and cell counting kit 8 assay after co-culture with rat’s BMSCs for 24 and 72 hours, respectively, and the osteogenic property was evaluated by alkaline phosphatase (ALP) staining and alizarin red staining after 7 and 14 days, respectively. Results NG-MBG@PDA-BBR and three control microspheres (MBG, MBG@PDA, and NG-MBG@PDA) were successfully constructed. Scanning electron microscopy showed that NG-MBG@PDA-BBR had a rough lamellar structure, while MBG had a smooth surface, and MBG@PDA and NG-MBG@PDA had a wrapped agglomeration structure. Specific surface area analysis showed that MBG had a mesoporous structure and had drug-loading potential. Low angle X-ray diffraction showed that NG was successfully loaded on MBG. The X-ray diffraction pattern contrast showed that all groups of microspheres were amorphous. Fourier transform infrared spectroscopy showed that NG and BBR peaks existed in NG-MBG@PDA-BBR. NG-MBG@PDA-BBR had good sustained drug release ability, and NG and BBR had early burst release and late sustained release. NG-MBG@PDA-BBR could inhibit the growth of Staphylococcus aureus and Escherichia coli, and the antibacterial ability was significantly higher than that of MBG, MBG@PDA, and NG-MBG@PDA (P<0.05). But there was a significant difference in biocompatibility at 72 hours among microspheres (P<0.05). ALP and alizarin red staining showed that the ALP positive area and the number of calcium nodules in NG-MBG@PDA-BBR were significantly higher than those of MBG and NG-MBG (P<0.05), and there was no significant difference between NG-MBG@PDA and NG-MBG@PDA (P>0.05). Conclusion NG-MBG@PDA-BBR have sustained release effects on NG and BBR, indicating that it has ideal dual performance of osteogenesis and antibacterial property.
The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson’s disease (PD). In this study, wild-type AB zebrafish and transgenic Tg (vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
目的 探讨单光子计算机断层扫描仪(SPECT)对抑郁症的疗效评估价值。 方法 2006年5月-2007年12月，选取32例未经治疗的原发性中、重度抑郁症患者，给予氟西汀治疗10周。治疗后根据临床疗效总评量表和汉密尔顿抑郁量表(HAMD)减分率作为疗效评定指标，将患者分为有效组21例，无效组11例。对所有患者于治疗前和治疗后分别进行99m锝-双半胱乙酯(99mTc-ECD)脑灌注显像。静脉注射99mTc-ECD 1 110 MBq，30 min后行脑断层显像，对显像结果分别进行目测及半定量分析两种方法进行判断。 结果 抑郁症患者出现的脑血流灌注减低区主要集中在前额叶、扣带回，经过治疗后好转的抑郁症患者脑血流灌注明显改善。可通过脑血流灌注显像评估抗抑郁治疗的疗效，左前额叶血流灌注越低，对氟西汀治疗效果越好。 结论 SPECT显像技术可视性较好，可用于评估抗抑郁治疗的疗效。
Excessive microglial activation and subsequent neuroinflammation lead to neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases such as Parkinson's disease. The objective of this study was to determine the involvement of chlorpyrifos (CPF) in the activation of microglia and production of inflammatory factors in response to CPF stimulation and the influence on the viability of dopaminergic (DA) neurons. We detected the change of BV-2 cells morphology and expression of inducible nitric oxide (iNOS), cyclooxygenase-2 (COX-2) mRNA and protein level upon CPF stimulation (0, 1, 3, 6, 12, 24 h) in BV-2 (mouse brain microglia) cells by reverse transcription polymerase chain reaction (RT-PCR) or Western blot. We randomly assigned BV-2 cells into CPF, menstruum dimethysulfoxide (DMSO) and normal saline (NS) groups. We stimulated The BV-2 cells in the CPF group with CPF, and we stimulated the two control groups with DMSO or NS for 12 hours, respectively. We then collected the used culture media from the culture dishes and centrifuged it to remove the detached cells. Then, we used the supernatants as microglial conditioned media. We treated SH-SY5Y neurons with various groups of microglial conditioned media for 24 hours. We observed the effect of conditioned media collected from BV-2 cell on the viability of dopaminergic cell lines SH-SY5Y using MTT assay. We found that inflammatory factors iNOS, COX-2 mRNA and protein levels were up-regulated upon CPF stimulation. Conditioned media from BV-2 upon CPF stimulation is toxic to SH-SY5Y. It might be concluded that the exposure to CPF may induce dopaminergic neuronal damage by the activation of inflammatory response, and a mechanism may be involved in Parkinson's disease pathogenesis.
ObjectiveTo study the effect of rotenone on rat substantia nigra dopamine (DA) in the nervous system and oxidative stress parameters (malondialdehyde and glutathione), the influence of rotenone on DA neurons toxic effect and its pathogenesis. MethodsThis study applied back subcutaneous injection of rotenone in rats [1.0 mg/(kg·d)], and used immunocytochemistry technique to detect changes in the expression of tyrosine kinase (TH) in 10 rats of the control group and 10 rats of the experimental group. Spectrophotometry was used to detect the change of oxidative stress parameters in rats (malondialdehyde and glutathione). ResultsDA neurons in rats had various degrees of damage. The TH immune response strength of rats in the substantia nigra and striatum decreased significantly. The number of immune response nigra TH positive neurons was significantly less in the experimental group than in the control group (P< 0.01). Spectrophotometer method was used to detect the midbrain nigra of glutathione, which was significantly less in the experimental group than in the control group (P<0.01). Malondialdehyde in the experimental group was significantly higher (P<0.01). ConclusionRotenone has obvious neurotoxicity, and can lead to the damage of DA neurons and obvious oxidative stress injury in rats, which provides an experimental basis for the pathogenesis of Parkinson's disease, and at the same time provides new targets for the treatment.