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.
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.
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.
Objective To systematically review the efficacy and safety of non-ergoline dopamine agonists (pramipexole, ropinirole, and rotigotine) and α2δ ligands (pregabalin and gabapentin-enacarbil) in the treatment of restless legs syndrome (RLS). Methods The PubMed, EMbase, The Cochrane Library, CBM, WanFang Data, and CNKI databases were electronically searched for randomized controlled trials (RCTs) assessing different medications for RLS from 2000 to 2021. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias of the included studies. The network meta-analysis was then performed using Stata 16.0 software and R 4.1.0 software. Results A total of 36 RCTs involving 7 666 patients were included. The results of the network meta-analysis showed that gabapentin-enacarbil decreased IRLS scores to the greatest extent among all drugs (MD=−6.42, 95%CI −8.8 to −4.16), was superior to pramipexole (MD=−3.27, 95%CI −6.54 to −0.15), and was associated with the highest CGI-I response rates (RR=1.73, 95%CI 1.52 to 2.00). In terms of tolerance and safety, patients receiving rotigotine presented an increased incidence of withdrawal due to adverse events. Ropinirole had the highest incidence of nausea. Headache was most common side effect in rotigotine, while the incidences of somnolence and dizziness were higher in gabapentin-enacarbil than other treatments. Conclusion Current evidence suggests that gabapentin-enacarbil may be the best treatment for RLS. Rotigotine is associated with the worst tolerance. For safety, nausea is most common in ropinirole, headache is most common for rotigotine, and patients receiving gabapentin-enacarbil show increased incidences of somnolence and dizziness.
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.
ObjectiveTo prepare dopamine modified and cartilage derived morphogenetic protein 1 (CDMP1) laden polycaprolactone-hydroxyapatite (PCL-HA) composite scaffolds by three-dimensional (3D) printing and evaluate the effect of 3D scaffolds on in vitro chondrogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).MethodsA dimensional porous PCL-HA scaffold was fabricated by 3D printing. Dopamine was used to modify the surface of PCL-HA and then CDMP-1 was loaded into scaffolds. The surface microstructure was observed by scanning electron microscope (SEM) and porosity and water static contact angle were also detected. The cytological experiment in vitro were randomly divided into 3 groups: group A (PCL-HA scaffolds), group B (dopamine modified PCL-HA scaffolds), and group C (dopamine modified and CDMP-1 laden PCL-HA scaffolds). The hBMSCs were seeded into three scaffolds, in chondrogenic culture conditions, the cell adhesive rate, the cell proliferation (MTT assay), and cell activity (Live-Dead staining) were analyzed; and the gene expressions of collagen type Ⅱ and Aggrecan were detected by real-time fluorescent quantitative PCR.ResultsThe scaffolds in 3 groups were all showed a cross-linked and pore interconnected with pore size of 400–500 μm, porosity of 56%, and fiber orientation of 0°/90°. For dopamine modification, the scaffolds in groups B and C were dark brown while in group A was white. Similarly, water static contact angle was from 76° of group A to 0° of groups B and C. After cultured for 24 hours, the cell adhesion rate of groups A, B, and C was 34.3%±3.5%, 48.3%±1.5%, and 57.4%±2.5% respectively, showing significant differences between groups (P<0.05). Live/Dead staining showed good cell activity of cells in 3 groups. MTT test showed that hBMSCs proliferated well in 3 groups and the absorbance (A) value was increased with time. The A value in group C was significantly higher than that in groups B and A, and in group B than in group A after cultured for 4, 7, 14, and 21 days, all showing significant differences (P<0.05). The mRNA relative expression of collagen type Ⅱ and Aggrecan increased gradually with time in 3 groups. The mRNA relative expression of collagen type Ⅱafter cultured for 7, 14, and 21 days, and the mRNA relative expression of Aggrecan after cultured for 14 and 21 days in group C were significantly higher than those in groups A and B, and in group B than in group A, all showing significant differences (P<0.05).ConclusionCo-culture of dopamine modified and CDMP1 laden PCL-HA scaffolds and hBMSCs in vitro can promote hBMSCs’ adhesion, proliferation, and chondrogenic differentiation.
Ｉｎ ｔｈｅ ａｃｕｔｅ ｈｅｍｏｒｒｈａｇｉｃ ｎｅｃｒｏｔｉｚｉｎｇ ｐａｎｃｒｅａｔｉｔｉｓ（ＡＨＮＰ）ｍｏｄｅｌ ｏｆ ｒａｔｓ ｉｎｄｕｃｅｄ ｂｙ ５％ ｓｏｄｉｕｍ ｔａｕｒｏｃｈｏｌａｔｅ，ａｆｔｅｒ ｔｒｅａｔｅｄ ｗｉｔｈ ｌｏｗ ｄｏｓｅ ｄｏｐａｍｉｎｅ〔５μｇ／（ｋｇ·ｍｉｎ）〕，ｔｈｅ ａｌｔｅｒｎａｔｉｏｎｓ ｏｆ ｍｅａｎ ａｒｔｅｒｉａｌ ｐｒｅｓｓｕｒｅ，ｐａｎｃｒｅａｔｉｃ ｍｉｃｒｏｆｌｏｗ，ｓｅｒｕｍ ａｍｙｌａｓｅ ａｎｄ ｌｉｐａｓｅ，ａｎｄ ｐａｎｃｒｅａｔｉｃ ｐａｔｈｏｈｉｓｔｏｌｏｇｙ ｗｅｒｅ ｓｔｕｄｉｅｄ．Ｔｈｅ ｒｅｓｕｌｔｓ ｓｈｏｗｅｄ ｔｈａｔ ｌｏｗ ｄｏｓｅ ｄｏｐａｍｉｎｅ ｃｏｕｌｄ ｉｎｃｒｅａｓｅ ｐａｎｃｒｅａｔｉｃ ｍｉｃｒｏｆｌｏｗ ｓｉｇｎｉｆｉｃａｎｔｌｙ ｗｈｉｌｅ ｍｅａｎ ａｒｔｅｒｉａｌ ｐｒｅｓｓｕｒｅ ｒｅｍａｉｎｅｄ ｓｔａｂｌｅ ｉｎ ｔｈｅ ｅａｒｌｙ ｓｔａｇｅ ｏｆ ＡＨＮＰ，ｉｔ ｃｏｕｌｄ ａｌｓｏ ｒｅｄｕｃｅ ｔｈｅ ｌｅｖｅｌｓ ｏｆ ｓｅｒｕｍ ａｍｙｌａｓｅ ａｎｄ ｌｉｐａｓｅ，ａｎｄ ａｍｅｌｉｏｒａｔｅ ｔｈｅ ｐａｔｈｏｌｏｇｉｃ ｓｅｖｅｒｉｔｙ ｏｆ ｐａｎｃｒｅａｔｉｔｉｓ．Ｔｈｅｓｅ ｓｕｇｇｅｓｔ ｔｈａｔ ｌｏｗ ｄｏｓｅ ｄｏｐａｍｉｎｅ ｃｏｕｌｄ ｂｅ ｕｓｅｄ ｔｏ ｔｒｅａｔ ｐａｎｃｒｅａｔｉｔｉｓ ｂｙ ｉｍｐｒｏｖｉｎｇ ｐａｎｃｒｅａｔｉｃ ｍｉｃｒｏｆｌｏｗ．
The application of dopamine agonists in Parkinson’s disease has been a hot topic in recent years. Can dopamine receptor agonists serve as the initial drugs for Parkinson’s disease? Does it improve the natural history of patients? Has it neuroprotective role? When and how to use dopamine receptor agonists? This article provides evidence on the pros and cons of dopamine receptor agonists in the treatment of Parkinson’s disease for helping clinical decision making.