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Introduction: Coronavirus disease-2019 (COVID-19) has affected more than 608 million people and has killed 6.5 million people in the world. A few studies showed traditional Chinese medicine can be beneficial for COVID-19 treatment. An herbal preparation Jin Si Herbal Tea (JS) was formulated with herbal extracts known for their potential to decrease spike protein and ACE2 interaction, 3CL, and TRPMSS2 protease activity, and thus aimed to evaluate the clinical course of JS co-treatment along with the usual treatment schedule given for severe COVID-19 patients. Methods: This retrospective cohort study included patients with severe COVID-19 admitted to Hualien Tzu Chi Hospital between June and July 2021. All the patients were co-treated with JS and the primary outcome was death. The secondary outcomes included laboratory exam, Ct value, clinical course, and hospital stays. There were 10 patients recruited in this study and divided into < 70 years and ⧠70 years groups (n = 5 in each group). Results: Older patients (â§70 years) had a higher Charlson Comorbidity Index, VACO index, and lower hemoglobin levels than < 70 years patients. The trend of lymphocyte count, LDH, D-dimer, and Ct value of non-survivors was not consistent with previous studies. The death rate was 20% and the recovery rate to mild illness in 14 days was 40%. Conclusion: In conclusion, this is the first clinical study of JS co-treatment in severe COVID-19 patients. JS co-treatment might reduce death rate and recovery time. Further large-scale clinical trials would be expected.
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Cognitive dysfunction is a common symptom in Parkinson's disease (PD). Serotonin4 (5-HT4) receptors are richly expressed in the dorsal hippocampus (dHIPP) and play an important role in cognitive activities. However, the mechanism underlying the role of dHIPP 5-HT4 receptors in PD-related cognitive dysfunction remains unclear. Here we found that unilateral 6-hydroxydopamine lesions of the medial forebrain bundle increased the protein expression of 5-HT4 receptors in the dHIPP, decreased hippocampal theta rhythm, and impaired working memory and hippocampus-dependent memory in the T-maze and hole-board test, respectively. Both activation and blockade of dHIPP 5-HT4 receptors (agonist BIMU8 and antagonist GR113808) improved working memory and hippocampus-dependent memory in the lesioned rats, but not in sham rats. Activation of dHIPP 5-HT4 receptors increased hippocampal theta rhythm in the lesioned rats. The neurochemical studies showed that injection of BIMU8, GR113808 or GR113808/BIMU8 in the dHIPP increased the levels of dopamine in the medial prefrontal cortex (mPFC), dHIPP and amygdala, and the level of 5-HT in the amygdala in the lesioned rats, but not in sham rats. Injection of GR113808 or GR113808/BIMU8 into the dHIPP also increased the levels of noradrenaline in the mPFC, dHIPP and amygdala only in the lesioned rats. These results suggest that activation or blockade of dHIPP 5-HT4 receptors may improve the cognitive impairments in parkinsonian rats, which may be due to the increase of hippocampal theta rhythm, up-regulated expressions of 5-HT4 receptors in the dHIPP and the changes in the levels of monoamines in the relative brain areas.
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Doença de Parkinson , Transtornos Parkinsonianos , Animais , Hipocampo/metabolismo , Oxidopamina , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismoRESUMO
BACKGROUND: The identification of post pulmonary vein isolation (PVI) gaps by activation and voltage maps is time-consuming. This study aimed to investigate the characteristics, efficiency and accuracy of LiveView dynamic display module (EnSite™ Dynamic Display; Abbott, Abbott Park, IL, USA) in unmasking post PVI gaps and conduction block line. METHOD: Twenty four patients with paroxysmal atrial fibrillation (PAF) who failed to achieve first-pass PVI or with recurrent PAF were enrolled. Ninety-six pulmonary veins (PVs) were evaluated, and gaps were identified in 25 (26.0%) PVs. The gap location was confirmed by activation and propagation maps; 110 frames on gaps and 118 frames on block lines were analyzed by using LiveView module. We defined isochronal crowding in the local activation time (LAT) mode as three colors between two adjacent electrodes. Each frame was classified as with or without isochronal crowding in LAT mode and one/continuous color or isochronal discontinuity in reentrant mode. The gray color inside the PVs was considered to represent conduction block. RESULT: The isochronal crowding could be found on both gap and block line in LAT mode, whereas isochronal discontinuity only presented on the block line in reentrant mode. The sensitivity and specificity of isochronal discontinuity or gray color in reentrant mode to identify block line were 61.0% and 100%, respectively. The sensitivity and specificity of isochronal crowding or gray color in LAT mode to identify block line were 71.2% and 71.8%, respectively. CONCLUSION: Reentrant mode in LiveView module is very specific in identifying block lines. We proposed an efficient, practical algorithm to differentiate the block line from PV gaps.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/cirurgia , Humanos , Veias Pulmonares/cirurgia , Tecnologia , Resultado do TratamentoRESUMO
Knee osteoarthritis (KOA) is a highly prevalent, chronic joint disorder, and it is a typical disease which can develop chronic pain. Our previous study has proved that endocannabinoid (2-AG)-CB1R-GABA-5-HT pathway is involved in electroacupuncture (EA) mediated inhibition of chronic pain. However, it is still unclear which among the 5-HT receptor subtype is involved in EA evoked 5-HT mediated inhibition of chronic pain in the dorsal spinal cord. 5-HT2A is a G protein-coupled receptor and it is involved in 5-HT descending pain modulation system. We found that EA treatment at frequency of 2 Hz +1 mA significantly increased the expression of 5-HT2A receptor in the dorsal spinal cord and intrathecal injection of 5-HT2A receptor antagonist or agonist reversed or mimicked the analgesic effect of EA in each case respectively. Intrathecal injection of a selective GABAA receptor antagonist Bicuculline also reversed the EA effect on pain hypersensitivity. Additionally, EA treatment reversed the reduced expression of GABAA receptor and KCC2 in the dorsal spinal cord of KOA mice. Furthermore, we demonstrated that intrathecal 5-HT2A receptor antagonist/agonist reversed or mimicked the effect of EA up-regulate of KCC2 expression, respectively. Similarly, intrathecal injection of PLC and PKC inhibitors prevented both anti-allodynic effect and up-regulation of KCC2 expression by EA treatment. Our data suggest that EA treatment up-regulated KCC2 expression through activating 5-HT2A-Gq-PLC-PKC pathway and enhanced the inhibitory function of GABAA receptor, thereby inhibiting chronic pain in a mouse model of KOA.
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Dor Crônica , Eletroacupuntura , Osteoartrite do Joelho , Simportadores , Animais , Dor Crônica/metabolismo , Dor Crônica/terapia , Camundongos , Osteoartrite do Joelho/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor 5-HT2A de Serotonina/metabolismo , Receptores de GABA-A/metabolismo , Serotonina/metabolismo , Medula Espinal/metabolismo , Simportadores/metabolismoRESUMO
In this work, we employed an asymmetric auxiliary organic ligand (1,1,1-trifluoroacetylacetone, Htfac) to further regulate the magnetic relaxation behavior of series of Dy2 single-molecule magnets (SMMs) with a N1,N3-bis(3-methoxysalicylidene)diethylenetriamine (H2L) ligand. Fortunately, an air-stable Dy2 complex, [Dy2(L)2(tfac)2] (1; Htfac = 1,1,1-trifluoroacetylacetone) was obtained at room temperature. A structural analysis indicated that some Dy-O or Dy-N bond lengths for 1 are not in the range of those for the complexes [DyIII2(L)2(acac)2]·2CH2Cl2 (Dy2-acac; Hacac = acetylacetone) and [DyIII2(L)2(hfac)2] (Dy2-hfac; Hhfac = hexafluoroacetylacetone), although the electron-withdrawing ability of tfac- is stronger than that of acac- but weaker than that of hfac-. Additionally, the Dy-O3/O3a (the two O atoms bridged to DyIII ions) bond lengths are also affected by the asymmetrical Htfc ligand. This indicated that the charge distribution of the coordination atoms around DyIII has been modified in 1, which leads to the fine-tuning of the magnetic relaxation behavior of 1. Magnetic studies indicated that the values of effective energy barrier (Ueff) for 1 and its diluted sample (2) are 234.8(3) and 188.0(6) K, respectively, which are both higher than the reported value of 110 K for the complex Dy2-hfac. More interestingly, 1 exhibits a magnetic hysteresis opening when T < 2.5 K at zero field, while the hysteresis loops of 2 are closed at a zero dc field. This discrepancy is due to the weak intramolecular exchange coupling in 2, which cannot overcome the QTM of the single DyIII ion. Ab initio calculations for 1 revealed that the charge distributions of the coordination atoms around DyIII ions were regulated and the intramolecular exchange coupling was indeed improved when the asymmetrical Htfc was employed as a ligand for the synthesis of this kind of Dy2 SMM.
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In this work, we first synthesized a Zn-Dy complex, [Zn6Dy2(L)6(tea)2(CH3OH)2]·6CH3OH·8H2O (H2L = N-3-methoxysalicylidene-2-amino-3-hydroxypyridine, teaH3 = triethanolamine, 1), by employing H2L, anhydrous ZnCl2, and Dy(NO3)3·5H2O reacting with auxiliary ligand teaH3 in the mixture of CH3OH and DMF. When teaH3 and the solvent CH3OH in the reaction system of 1 were replaced by the auxiliary ligand 2,6-pyridinedimethanol (pdmH2) and the solvent MeCN, another Zn-Dy complex, [Zn4Dy4(L)6(pdm)2(pdmH)4]·10CH3CN·5H2O (2), was obtained. For 1, its crystal structure can be viewed as a dimer of two Zn3DyIII units. However, for 2, four DyIII form a zigzag arrangement, and each of its terminals linked two ZnII ions. Interestingly, although the structural topologies of 1 and 2 are different, the coordination geometries of DyIII in 1 and 2 are all triangular dodecahedron (TDD-8). The difference is that the continuous shape measure (CShM) values of DyIII in 1 are larger than the corresponding values in 2. Magnetic investigation revealed that the diluted sample 1@Y exhibits two magnetic relaxation processes, while 2 only exhibits a single relaxation process. Ab initio calculations indicated that, in the crystal lattice of 1, two complexes exhibiting slightly different CShM values of DyIII result in the double relaxation behavior of 1@Y. However, for 2, one of two DyIII fragments possesses a fast quantum tunneling of magnetization (QTM), resulting in its magnetic process presented at T < 1.8 K, so 2 exhibits single relaxation behavior. More importantly, the theoretical calculations also clearly indicated that the weak ligation at equatorial sites of DyIII in 1 and 2 ensure 1@Y and 2 possess SMM behavior, although the coordination geometry of DyIII (TDD-8) in 1 and 2 severely deviates from the ideal polyhedron and its axial symmetry is low.
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Depression is a common non-motor symptom in Parkinson's disease (PD). Although serotonin4 (5-HT4) receptors and the dorsal hippocampus (dHIP) are regarded to be involved in the depression, the mechanism underlying the effects of 5-HT4 receptors in the dHIP on PD-related depression should be further investigated. In the present study, unilateral 6-hydroxydopamine lesions of the medial forebrain bundle (MFB) increased the expressions of 5-HT4 receptors and its co-localization with glutamate neurons in the CA1, CA3 and dentate gyrus. Additionally, MFB lesions induced depressive-like behaviors in the sucrose preference and forced swimming tests. The activation or blockade of dHIP 5-HT4 receptors produced antidepressant effects in the MFB lesioned rats but not in control rats. Neurochemical results showed no changes of monoamines levels in the striatum, medial prefrontal cortex (mPFC), lateral habenula (LHb), and ventral hippocampus (vHIP) in control rats after intra-dHIP injection of 5-HT4 receptors agonist BIMU8 (26 µg/rat), antagonist GR 113808 (16 µg/rat) or GR 113808/BIMU8 (26 µg/16 µg/rat). But in the lesioned rats, BIMU8, GR113808 or GR 113808/BIMU8 injection increased dopamine levels in the striatum, mPFC, LHb, and vHIP and increased 5-HT levels in the LHb. Intra-dHIP injection of GR 113808 or GR 113808/BIMU8 also increased the noradrenaline levels in the mPFC and LHb. All these results suggest that activation or blockade dHIP 5-HT4 receptors produce antidepressant effects in the hemiparkinsonian rats, which may be related to the upregulation of 5-HT4 receptors in the dHIP and the changes of monoamines in the limbic and limbic-related brain regions.
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BACKGROUND: The 5-hydroxytryptamine (5-HT) neurotransmitter system and lateral habenula (LHb) are involved in the regulation of depression, while the mechanisms remain to be clarified. OBJECTIVES: The effects and possible mecha-nism underlying activation or blockade of 5-HT4 receptors (5-HT4Rs) in the LHb in depression were investigated by behavioral and neurochemical methods based on a Parkinson's disease (PD) rat model. METHOD: 6-Hydroxydopamine (6-OHDA) was injected unilaterally into the substantia nigra pars compacta to establish the PD rat model. The depressive-like behaviors were measured by the forced swimming test (FST) and sucrose preference test (SPT). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by a neurochemical method. RESULTS: The 6-OHDA lesions increased the immobility time in the FST and decreased the sucrose consumption in the SPT, suggesting the induction of depressive-like behaviors. Intra-LHb injection of BIMU-8 (5-HT4R agonist) or GR113808 (5-HT4R antagonist) produced antidepressant effects in the lesioned rats. Intra-LHb injection of BIMU-8 significantly increased the DA levels in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHip), increased the 5-HT level in the mPFC and decreased the NA level in the vHip only in the lesioned rats, while intra-LHb injection of GR113808 changed DA, NA and 5-HT levels in the mPFC, LHb and vHip in both sham and the lesioned rats. CONCLUSIONS: All these results suggest that activation or blockade of the LHb 5-HT4Rs produce antidepressant effects in the 6-OHDA-lesioned rats, which are related to the changes of monoamines in the limbic and limbic-related regions.
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Antidepressivos/farmacologia , Comportamento Animal , Depressão , Habenula , Hipocampo , Doença de Parkinson , Córtex Pré-Frontal , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Habenula/efeitos dos fármacos , Habenula/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Norepinefrina/metabolismo , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Serotonina/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/administração & dosagem , Antagonistas do Receptor 5-HT4 de Serotonina/administração & dosagemRESUMO
With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the incidence of coronavirus disease (COVID-19) increases each day. To date, there is no specific anti-SARS-CoV-2 drug. The usual approach to treating COVID-19 is treating its symptoms. However, this approach is limited by the different conditions of each area. We treated a 57-year-old man who was initially diagnosed with a severe type of the infection, but he progressed to a critical condition and eventually died. We learned valuable lessons from this case. The first lesson is the need to use immediate invasive mechanical ventilation if there is no obvious improvement after using non-invasive ventilation for several hours, which directly affects the prognosis. Another lesson is the risk involved in transferring severe COVID-19 patients. In the process of transfer, various threats may be encountered at any time. Thus, accurate assessment of the patient's condition and strict medical conditions are highly required. During the patient's 25-day treatment, we performed cardiopulmonary resuscitation twice. Currently, many patients require invasive mechanical ventilation and transfer to a superior hospital. We hope our findings will provide some advice and help for treating severe and critical COVID-19 cases.
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BACKGROUND: Depression is one of the most common neuropsychiatric disturbances in Parkinson's disease (PD), but its pathophysiology is not definite. Lines of evidence have indicated that the hippocampus and serotonin 1A (5-HT1A) receptors are related to the regulation of depression. OBJECTIVE: The purpose of the present study was to observe the effect of 5-HT1A receptors in the dorsal hippocampus (dHIP) on PD-related depression in rats. METHODS: Unilateral 6-hydroxydopamine lesioning of the medial forebrain bundle (MFB) was used to establish the hemiparkinsonian rat model. The effects of intra-dHIP injection of the 5-HT1A receptor -agonist 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) or antagonist WAY-100635 on depressive-like behaviors were observed in sucrose preference and forced swim tests in control and lesioned rats. Monoamine levels including dopamine (DA), 5-HT, and noradrenaline (NA) in depression-related brain regions were determined by a neurochemical method in all groups. RESULTS: Behavioral results showed that MFB lesions induced depressive-like behaviors. Intra-dHIP injection of 8-OH-DPAT produced antidepressant effects, while WAY-100635 induced or increased the depressive-like behaviors in both control and the lesioned rats. Neurochemical results found that intra-dHIP injection of 8-OH-DPAT significantly increased DA and 5-HT levels in the medial prefrontal cortex (mPFC), lateral habenula (LHb), ventral hippocampus and amygdala in the lesioned group and decreased NA levels in the mPFC and LHb in the control group. Moreover, after injection of WAY-100635, NA levels in all these regions of the lesioned group were significantly increased. CONCLUSIONS: These findings suggest that hippocampal 5-HT1A receptors regulate depression and PD-related depression by neurochemical mechanisms.
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Comportamento Animal/efeitos dos fármacos , Depressão , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Doença de Parkinson/complicações , Receptor 5-HT1A de Serotonina/metabolismo , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Animais , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/metabolismo , Modelos Animais de Doenças , Habenula/efeitos dos fármacos , Habenula/metabolismo , Masculino , Feixe Prosencefálico Mediano/lesões , Piperazinas/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT1 de Serotonina/administração & dosagem , Antagonistas da Serotonina/administração & dosagemRESUMO
Although the dorsal hippocampus (dHPC) and serotonin1A (5-HT1A) receptor are involved in cognition, their roles in cognitive impairments in Parkinson' disease (PD) are still unclear. In the present study, the effects of the 5-HT1A receptor agonist 8-OH-DPAT and antagonist WAY100635 administrated into the dHPC of rats were assessed in T-maze rewarded alternation test for working memory and in hole-board test for long-term habituation. Unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle in rats impaired working memory and long-term habituation, decreased dopamine (DA) levels in the medial prefrontal cortex (mPFC), dHPC and ventral hippocampus (vHPC), and decreased the mean density of 5-HT1A receptors and co-localization of 5-HT1A receptor and excitatory amino acid carrier 1-immunoreactive (EAAC1-ir) neurons in the dHPC compared to sham-operated rats. Activation of dHPC 5-HT1A receptors by local infusion of 8-OH-DPAT impaired working memory and long-term habituation in both sham-operated and the 6-OHDA-lesioned rats. Furthermore, blockade of dHPC 5-HT1A receptors by WAY100635 improved the memories in the 6-OHDA-lesioned rats, but had no effects in sham-operated rats. Additionally, dHPC injection of 8-OH-DPAT decreased noradrenaline (NA) levels, increased 5-HT levels in the mPFC, dHPC and vHPC in sham-operated and lesioned rats, while WAY100635 increased DA and NA levels only in lesioned rats. The results of the present study suggest that dHPC 5-HT1A receptors regulate cognitive impairments in PD by changes of monoamines in the related brain regions.
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Memória/fisiologia , Doença de Parkinson/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Modelos Animais de Doenças , Dopamina/metabolismo , Habituação Psicofisiológica/fisiologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Feixe Prosencefálico Mediano/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Neurônios/metabolismo , Doença de Parkinson/fisiopatologia , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/fisiopatologia , Piperazinas/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/fisiologia , Serotonina/metabolismo , Agonistas do Receptor de Serotonina/farmacologia , Lobo Temporal/metabolismoRESUMO
Four chair-like hexanuclear Fe-Ln complexes containing mixed organic ligands, namely, [Fe4Ln2{(py)2CO2}4(pdm)2(NO3)2(H2O)2Cl4]·xCH3CN·yH2O (Ln = GdIII (1, x = 1, y = 0), DyIII (2, x = 1, y = 1), HoIII (3, x = 0, y = 2), and ErIII (4, x = 1, y = 3); (py)2CO2H2 = the gem-diol form of di-2-pyridyl ketone and pdmH2 = 2,6-pyridinedimethanol) have been obtained by employing di-2-pyridyl ketone and 2,6-pyridinedimethanol reacting with FeCl3 and Ln(NO3)3 in MeCN. The structures of 1-4 are similar to each other except for the number of lattice solvent molecules. Four FeIII and two LnIII in these complexes comprise a chair-like core with the "body" constructed by four FeIII ions and the "end" constructed by two LnIII ions. Among the four compounds, 2 shows field-induced single molecule magnet behavior as revealed by ac magnetic susceptibility studies, with the effective energy barrier and the pre-exponential factor of 22.07 K and 8.44 × 10-7 s, respectively. Ab initio calculations indicated that, among 2_Dy, 3_Ho and 4_Er fragments, the energy gap between the lowest two spin-orbit states for 2_Dy is the largest, while the tunneling gap for 2 is the smallest. These might be the reasons for complex 2 exhibiting SMM behavior. Additionally, the orientations of the magnetic anisotropy of DyIII in 2 were obtained by electrostatic calculations and ab initio calculations, both indicating that the directions of the main magnetic axis of Dy1 ions are almost aligned along Dy1-O5 (O5 from the pdm2- ligand).
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Four tetranuclear 3d-4f complexes, namely [Fe2Ln2(L)2(teaH)2(Cl)2](NO3)2·4CH3CN (H2L = N1,N3-bis(3-methoxysalicylidene)diethylenetriamine, teaH3 = triethanolamine, Ln = Dy for 1 and Ln = Gd for 1') and [Co2Ln2(L)2(pdm)2(CH3COO)2(CH3OH)2](NO3)2·xCH3OH·yH2O (pdmH2 = 2,6-pyridinedimethanol, Ln = Dy, x = 5 and y = 2.5 for 2 and Ln = Gd, x = 6 and y = 1.5 for 2'), have been reported. Two FeIII and two DyIII in 1 formed a zigzag Fe1-Dy1-Dy1a-Fe1a arrangement with a Fe1-Dy1-Dy1a angle of 105.328(3)°. However, in contrast to 1, two CoIII and two DyIII ions in 2 formed a more linear Co1-Dy1-Dy1a-Co1a arrangement with a Co1-Dy1-Dy1a angle of 141.86(2)°. Additionally, two DyIII ions in 1 are eight-coordinated with a triangular dodecahedron geometry, while two DyIII ions in 2 adopt nine-coordination with a muffin geometry. Magnetic studies revealed slow magnetic relaxation behavior for 1, with an energy barrier Ea of 6.9 K. For 2, single molecule magnet behavior was presented under a zero dc field with an effective energy barrier Ueff of 64.0(9) K. Ab initio calculations for 1 and 2 indicate that compared to 2, complex 1 has a larger transversal magnetic moment of its ground Kramers doublets (KD) and a larger value of the tunnelling parameter (Δt) for the exchanged coupled ground state, which may result in poor single molecule magnet behavior for 1.
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Two trinuclear copper phosphonate complexes, [Cu3 (pda)3 (tBuPO3 )]â 2(Et3 NH) (1) and [Cu3 (pda)3 (PhPO3 )]â 2(Et3 NH) (2), have been synthesized and investigated by a combination of X-ray crystallography, PXRD, magneto- and electrochemistry, EPR, in situ UV-vis spectroelectrochemistry and DLS. The two complexes feature almost identical crystal structures, the anions of which are both supported by pda2- and tBuPO3 2- /PhPO3 2- groups, bridging three five-coordinated CuII atoms to form a crown-like structure. This is the first time that trinuclear copper phosphonate complexes have been isolated and characterized. Magnetic susceptibility measurements reveal that complexes 1 and 2 both display overall ferromagnetic characters, but with different exchange interactions between the metal ions within the two clusters. The electrocatalytic activity for water oxidation of the two complexes was preliminarily investigated, which reveals that both of the two complexes can carry out electrocatalytic water oxidation in a neutral system owing to the introduction of phosphonate ligands into the complexes, with a TOF of about 0.82â s-1 (1) and 0.58â s-1 (2), respectively. We propose that the presence of phosphonate ligands may affect the magnetic property and catalytic activity of the complexes.
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Objectives: This study aimed to investigate the effect of serotonin6 (5-HT6) receptors in the dorsal hippocampus (dHip) on the regulation of Parkinson's disease (PD)-associated anxiety. Methods: We examined whether intra-dHip injection of both 5-HT6 receptor agonist and antagonist was involved in the regulation of anxiety-like behaviors in sham-operated rats and rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle by the open-field and elevated plus maze (EPM) tests. Four weeks after injection of 6-OHDA, the concentrations of dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) in relative related brain regions were measured by reverse-phase high-performance liquid chromatography. Results: In sham-operated rats, intra-dHip injection of both 5-HT6 receptor agonist WAY208466 (3 and 6 µg/rat) and antagonist SB258585 (4 µg/rat) increased the percentage of time spent in the center area in the open-field test and percentages of open arm entries and open arm time in EPM test, indicating that induced anxiolytic effects. In the lesioned rats, WAY208466 (1.5, 3 and 6 µg/rat) produced anxiolytic responses, whereas SB258585 (2 and 4 µg/rat) produced anxiogenic effects. Neurochemical results showed that intra-dHip injection of WAY208466 (6 µg/rat) decreased NA level in the amygdala, and SB258585 (4 µg/rat) increased DA levels in the dHip and vHip in sham-operated rats, whereas WAY208466 increased DA levels in the dHip, vHip, and amygdala in the lesioned rats. Discussion: dHip 5-HT6 receptors are involved in the regulation of anxiety-like behaviors, which may be mediated through different neurochemical mechanisms, and the dHip is an important site involved in these effects. Abbreviation: PD: Parkinson's disease;6-OHDA: 6-hydroxydopamine; dHip: dorsal hippocampus; vHip: ventral hippocampus; 5-HT: serotonin; MFB: medial forebrain bundle; DA: dopamine; NA: noradrenaline; EPM: elevated plus-maze; GABA: gamma-aminobutyric acid; BLA: basolateral amygdala.
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Dopamina/metabolismo , Doença de Parkinson/tratamento farmacológico , Piperazinas/farmacologia , Serotonina/metabolismo , Sulfonamidas/farmacologia , Animais , Ansiolíticos , Ansiedade/tratamento farmacológico , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Masculino , Doença de Parkinson/complicações , Ratos Sprague-Dawley , Receptores de Serotonina/metabolismoRESUMO
Objective: The aim of the present study was to investigate the effects and mechanism of 6-hydroxydopamine (6-OHDA) lesions and serotonin 4 (5-HT4) receptors in the lateral habenula (LHb) on Parkinson's disease (PD) related working memory. Methods: The working memory was measured by the T-maze rewarded alternation test in sham rats and rats with unilateral 6-OHDA lesions of substantia nigra pars compacta (SNc). The concentrations of dopamine (DA), noradrenaline (NA) and 5-HT in the related brain regions were measured by neurochemistry.Results: The results showed that 6-OHDA lesions of the SNc induced working memory impairment. Intra-LHb injection of 5-HT4 receptor agonist BIMU-8 (2, 4 or 8 µg) and antagonist GR113808 (1, 3.3 or 10 µg) improved the working memory only in the lesioned rats. Intra-LHb injection of BIMU-8 (8 µg) significantly increased DA levels in the medial prefrontal cortex, dorsal hippocampus and amygdala in the lesioned rats but not in sham rats. BIMU-8 did not change NA and 5-HT levels in the related brain regions in both sham and lesioned rats. Intra-LHb injection of GR113808 (10 µg) changed DA, NA and 5-HT levels in related brain regions in both sham and the lesioned rats. In addition, the 5-HT4 receptor-positive neurons in the LHb increased significantly in the lesioned rats.Conclusion: These findings suggested that unilateral lesions of the SNc induced working memory impairment and up-regulation of 5-HT4 receptors in the LHb. Activation and blockade of LHb 5-HT4 receptors improved working memory, that were related to the change of monoamines levels. Abbreviation: 6-OHDA: 6-hydroxydopamine; serotonin:5-HT; LHb: lateral habenula; PD: Parkinson's disease; SNc: substantia nigra pars compacta; DA: dopamine; NA: noradrenaline.
Assuntos
Habenula/fisiologia , Memória de Curto Prazo/fisiologia , Transtornos Parkinsonianos/fisiopatologia , Transtornos Parkinsonianos/psicologia , Receptores 5-HT4 de Serotonina/fisiologia , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/farmacologia , Encéfalo/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/administração & dosagem , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Habenula/efeitos dos fármacos , Indóis/administração & dosagem , Indóis/farmacologia , Masculino , Aprendizagem em Labirinto/fisiologia , Memória de Curto Prazo/efeitos dos fármacos , Microinjeções , Norepinefrina/metabolismo , Oxidopamina , Transtornos Parkinsonianos/metabolismo , Ratos , Receptores 5-HT4 de Serotonina/efeitos dos fármacos , Receptores 5-HT4 de Serotonina/metabolismo , Serotonina/metabolismo , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia , Substância Negra/efeitos dos fármacos , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologiaRESUMO
An unprecedented Tb(iii) polycarboxylate, {[Tb4(TTHA)2(H2O)4]·7H2O}n (1), has been synthesized. It possesses an efficient proton transfer pathway formed by water molecules and carboxyl groups, which exhibits proton conductivity over 10-2 S cm-1 at 295-358 K and 98% relative humidity.
RESUMO
In this work, we report the syntheses, crystal structures and magnetic properties of three novel Zn-Ln mixed metal complexes, namely [Zn4Dy2(L1)2(L2)2(N3)2]Cl2·2H2O (1), [Zn4Tb2(L1)2(L2)2(Cl)2][ZnN3Cl3]·2H2O (2), and [Zn4Gd2(L1)2(L2)2(Cl)2][ZnN3Cl3]·2H2O (3), in which L12- and L23- were formed from the ligand L [L = N1,N3-bis(3-methoxysalicylidene)diethylenetriamine] through in situ reactions. Interestingly, carbon dioxide in air was absorbed in the process of forming carbamate ligand L23-; this can be ascribed to the insertion of CO2 into M-N amide bonds. Moreover, 1 and 2 represent the first series of 3d-4f SMMs containing carbamate ligands by fixation of CO2 in air. Single-crystal X-ray diffraction analyses reveal that the crystal structures of 1 and 2 are anion-dependent, i.e., the apical positions of the two ZnII ions in 1 and 2 are occupied by an N atom of N3- and by Cl-, respectively. However, the topologies of 2 and 3 are similar. Two ZnII ions and one LnIII (Ln = Dy (1), Tb (2) and Gd (3)) form nearly linear trinuclear [Zn2Ln] units which are double-bridged by two L23- ligands. Magnetic studies reveal that two complexes show single molecule magnet behavior under a direct current (dc) field, with effective energy barriers (Ueff) of 30.66(5) K for 1 and 8.87(3) K for 2. Ab initio calculations reveal that the DyIII ions in 1 and the TbIII ions in 2 are axial in nature; however, a difference in the tunnel splitting of 1 and 2 leads to variation in the magnetization blockades of the two complexes. Theoretical calculations also indicate that the directions of the main magnetic axes severely deviate from the coordination atoms of the first spheres of DyIII and TbIII in 1 and 2; thus further results in poor SMM behavior of the two complexes.
RESUMO
L-DOPA-induced dyskinesia (LID) is a frequent complication of chronic L-DOPA therapy in the clinical treatment of Parkinson's disease (PD). The pathogenesis of LID involves complex molecular mechanisms in the striatum. Metabolomics can shed light on striatal metabolic alterations in LID. In the present study, we compared metabolomics profiles of striatum tissue from Parkinsonian rats with or without dyskinetic symptoms after chronic L-DOPA administration. A liquid chromatography-mass spectrometry based global metabolomics method combined with multivariate statistical analyses were used to detect candidate metabolites associated with LID. 36 dysregulated metabolites in the striatum of LID rats, including anandamide, 2-arachidonoylglycerol, adenosine, glutamate and sphingosine1-phosphate were identified. Furthermore, IMPaLA metabolite set analysis software was used to identify differentially regulated metabolic pathways. The results showed that the metabolic pathways of "Retrograde endocannabinoid signaling", "Phospholipase D signaling pathway", "Glycerophospholipid metabolism" and "Sphingolipid signaling", etc. were dysregulated in LID rats compared to non-LID controls. Moreover, integrated pathway analysis based on results from the present metabolomics and our previous gene expression data in LID rats further demonstrates that aberrant "Retrograde endocannabinoid signaling" pathway might be involved in the development of LID. The present results provide a new profile for the understanding of the pathological mechanism of LID.
Assuntos
Antiparkinsonianos/efeitos adversos , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Discinesia Induzida por Medicamentos/metabolismo , Levodopa/efeitos adversos , Transtornos Parkinsonianos/tratamento farmacológico , Animais , Antiparkinsonianos/farmacologia , Apomorfina/farmacologia , Ácidos Araquidônicos/farmacologia , Biomarcadores/metabolismo , Agonistas de Receptores de Canabinoides/farmacologia , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Levodopa/farmacologia , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica , Atividade Motora/efeitos dos fármacos , Oxidopamina , Transtornos Parkinsonianos/complicações , Transtornos Parkinsonianos/metabolismo , Alcamidas Poli-Insaturadas/farmacologia , Ratos Sprague-DawleyRESUMO
We report the syntheses, crystal structures, and magnetic properties of two 3d-4f heterometallic compounds; namely, [Mn8Ln2O2(OH)2{(py)2CO2}4(teaH)4(CH3COO)6]·6CH3CN·2H2O (LnIII = Dy (1), Tb (2); (py)2CO2H2 = the gem-diol form of di-2-pyridyl ketone, teaH3 = triethanolamine). Both compounds were prepared by the reaction of Mn(OAc)2·4H2O, Ln(NO3)3·5H2O (Ln = Dy and Tb) with the ligands di-2-pyridyl ketone and triethanolamine in MeCN, and they crystallize in the monoclinic space group C2/c. [Mn8Ln2] complexes have not been reported before, and the metallic cores of both complexes were unprecedented. In these cores, two Dy or Tb and two Mn ions comprised a well-known butterfly topology, with three of the remaining six Mn atoms each being situated on either side of the butterfly, linked through two µ3-O2- ions. Six MnIII and two MnII were in six-coordinated distorted octahedrons and two LnIII ions were in nine-coordinated distorted muffins. Interestingly, the coordination sites of LnIII ions are occupied by six O and two N atoms from two teaH2- ligands and one µ3-O2- atom, without the presence of coordinated solvent molecules such as H2O and small anions such as NO3- ions, which is rare in 3d-4f complexes. Remarkably, alternating current (ac) magnetic susceptibility measurements revealed that both complexes displayed dynamic anisotropic magnetic behaviour. The effective energy barrier (Ueff) of complex 2 was estimated to be 18.97 K through high frequency (111-9111 Hz) ac susceptibility measurements. The low symmetry of the coordination configuration of Ln3+ in 1 and 2 may be responsible for the small energy barriers of these two compounds.