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.
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．
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 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.
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.
Abstract： Objective To use tissue Doppler strain rate imaging to evaluate the impact of low dose dopamine and milrinone on systolic and diastolic function of the left ventricle of patients undergoing heart valve replacement. Methods Forty patients undergoing selective heart valve replacement in West China Hospital of Sichuan University between March and May 2011 were included in this study. All the patients were randomized into 2 groups with 20 patients in each group： milrione group and dopamine group. After anesthesia induction and before cardiopulmonary bypass setup， left ventricular ejection fraction （LVEF） was measured by echocardiography. Tissue Doppler strain rate imaging was used to measure the left ventricular lateral wall and midventricular segment from the four-chamber view， which was compared with Doppler parameters. Results LVEF， ratio of early-diastolic to end-diastolic velocity （E/A） of transmitral flow， ratio of mitral inflow velocity to early diastolic velocity in the annulus （E/Et） of both 2 groups were significantly different between before and after dopamine and milrinone administration （P＜0. 05）. In the milrinone group， 4 segments systolic peak velocity （Vs）， 1 segment early diastolic peak velocity （Ve）， 4 segments late diastolic peak velocity （Va）， 3 segments Ve/Va ratio， 2 segments systolic peak strain rate （SRs）， 2 segments late diastolic peak strain rate （SRa）， and 3 segments early diastolic peak strain rate SRe/SRa ratio after dopamine and milrinone administration were significantly higher than those before dopamine and milrinone administration （P＜0. 05）. In the dopamine group， 4 segments systolic peak velocity （Vs）， 1 segment Ve， 4 segments Va， 1 segment Ve/Va ratio， 2 segments SRs， 1 segment SRe， 1 segment SRa， and 1 segment SRe/SRa ratio after dopamine and milrinone administration were significantly higher than those before dopamine and milrinone administration （P＜0.05）. To compare the milrione group and dopamine group after medication administration， 2 segments Vs， 4 segments Va， 1 segment SRe， 1 segment SRa， 2 segments Ve/Va ratio， and 2 segments SRe/SRa ratio of the milrione group were significantly higher than those of the dopamine group （P＜0.05）， and 1 segment Vs， two segments SRs of the milrione group were significantly lower than those of the dopamine group （P＜0.05）. Conclusion Both milrinone and dopamine can improve left ventricular systolic function of perioperative patients undergoing heart valve replacement assessed by tissue Doppler strain rate imaging， while milrinone can improve the diastolic function of the left ventricle on the long axis more significantly.
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.