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1.
Org Lett ; 22(3): 976-980, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-31984752

RESUMO

Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations with ortho-cyanomethylbenzaldehydes. These amine α-C-H bond functionalization reactions are promoted by acetic acid. The resulting ß-aminonitriles can be converted to the corresponding ß-aminoalcohols in diastereoselective fashion.


Assuntos
Amino Álcoois/síntese química , Benzaldeídos/química , Tetra-Hidroisoquinolinas/química , Ácido Acético/química , Amino Álcoois/química , Estrutura Molecular , Oxirredução , Estereoisomerismo
2.
Aust J Rural Health ; 28(2): 124-131, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31960537

RESUMO

OBJECTIVE: To study the effect of nurse-led counselling on the anxiety symptoms and the quality of life following percutaneous coronary intervention for stable coronary artery disease. DESIGN: Randomised control trial. SETTING: Rural and remote China. PARTICIPANTS: Rural and remote patients were consecutively recruited from a medical centre located in China between January and December 2014. INTERVENTIONS: The control group received standard pre-procedure information from a ward nurse on the processes of the hospitalisation and percutaneous coronary intervention, and post-procedural care. The intervention group received a structured 30-minute counselling session the day before and 24 hours after the percutaneous coronary intervention, by nurse consultants with qualifications in psychological therapies and counselling. The health outcomes were assessed by a SF-12 scale and the Seattle Angina Questionnaire at 6 and 12 months after percutaneous coronary intervention. The anxiety and depression symptoms were evaluated by a Zung anxiety and depression questionnaire. MAIN OUTCOME MEASURES: Cardiac outcomes, quality of life and mental health status. RESULTS: Eighty patients were randomly divided into control (n = 40) and intervention groups (n = 40). There was a significant increase in the scores of the three domains of Seattle Angina Questionnaire 12 months after percutaneous coronary intervention in the intervention group (P < .01). The mental health and physical health scores also increased (P < .01). In the control group, the mean scores of Zung self-rating anxiety scale 12 months following percutaneous coronary intervention were higher than the baseline scores, and higher than in the intervention group (P < .01). CONCLUSIONS: Counselling by a clinician qualified in psychological therapies and counselling significantly reduces anxiety symptoms and improves quality of life.


Assuntos
Ansiedade/enfermagem , Intervenção Coronária Percutânea/psicologia , Intervenção Psicossocial , Qualidade de Vida , Idoso , China/epidemiologia , Doença da Artéria Coronariana/cirurgia , Depressão/enfermagem , Feminino , Nível de Saúde , Humanos , Masculino , Saúde Mental , Pessoa de Meia-Idade , População Rural , Inquéritos e Questionários
3.
SynOpen ; 4(4): 123-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-34327302

RESUMO

Amines such as 1,2,3,4-tetrahydroisoquinoline undergo redox-neutral annulations with ortho-(nitromethyl)benzaldehyde. Benzoic acid acts as a promoter in these reactions, which involve concurrent amine α-C-H bond and N-H bond functionalization. Subsequent removal of the nitro group provides access to tetrahydroprotoberberines not accessible via typical redox-annulations. Also reported are decarboxylative annulations of ortho-(nitromethyl)benzaldehyde with proline and pipecolic acid.

4.
Rural Remote Health ; 19(2): 5270, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31113205

RESUMO

INTRODUCTION: Patient self-management skills are an important part of heart failure (HF) management. However, there is a lack of knowledge about the effectiveness of nurse-led education on patient self-management and the associated clinical outcomes of rural Chinese patients with chronic heart failure (CHF). As such, this study was designed to evaluate the impact of a nurse-led education program on patient self-management and hospital readmissions in rural Chinese patients with CHF. METHODS: Ninety-six patients in the eastern Chinese province of Shandong with CHF were randomly divided into intervention and control groups. A structured education program was delivered to the intervention group during hospitalization and after discharge. Control group patients were managed as per clinical guidelines without structured education. Medication adherence, dietary modifications, social support, and symptom control were assessed 12 months after the educational intervention. RESULTS: The mean score of medication adherence, dietary modifications, social support and symptom control in the intervention group was higher than in the control group at the end of the study (p<0.01). The readmission rates for HF in the intervention and control group were 10.4% and 27.1%, respectively (p=0.036). CONCLUSIONS: This study has demonstrated that a structured education program was associated with a significant improvement in medication adherence, dietary modifications, social support, and symptom control in rural CHF patients. Furthermore, this program was associated with a significant reduction in hospital readmission. This study indicates that implementation of a nurse-led education program improves self-management and clinical outcomes of rural CHF patients, who may not have regular access to cardiac management services as per metropolitan populations.


Assuntos
Insuficiência Cardíaca/enfermagem , Educação de Pacientes como Assunto/métodos , Readmissão do Paciente/estatística & dados numéricos , Autogestão/métodos , Adulto , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Relações Enfermeiro-Paciente
5.
ChemMedChem ; 14(3): 303-309, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-30589226

RESUMO

Muscarinic acetylcholine receptors (mAChRs) have five distinct subunits (M1 -M5 ) and are involved in the action of the neurotransmitter acetylcholine in the central and peripheral nervous system. Attributed to the promising clinical efficacy of xanomeline, an M1 /M4 -preferring agonist, in patients of schizophrenia and Alzheimer's disease, M1 - or M4 -selective mAChR modulators have been developed that target the topographically distinct allosteric sites. Herein we report the synthesis and preliminary evaluation of 11 C-labeled positron emission tomography (PET) ligands based on a validated M4 R positive allosteric modulator VU0467485 (AZ13713945) to facilitate drug discovery. [11 C]VU0467485 and two other ligands were prepared in high radiochemical yields (>30 %, decay-corrected) with high radiochemical purity (>99 %) and high molar activity (>74 GBq µmol-1 ). In vitro autoradiography studies indicated that these three ligands possess moderate-to-high in vitro specific binding to M4 R. Nevertheless, further physiochemical property optimization is necessary to overcome the challenges associated with limited brain permeability.


Assuntos
Agonistas Muscarínicos/química , Piridazinas/química , Receptor Muscarínico M4/análise , Animais , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono , Ligantes , Estrutura Molecular , Agonistas Muscarínicos/síntese química , Agonistas Muscarínicos/farmacologia , Tomografia por Emissão de Pósitrons , Piridazinas/síntese química , Piridazinas/farmacologia , Ratos , Receptor Muscarínico M4/agonistas
6.
Eur J Med Chem ; 157: 898-908, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-30145376

RESUMO

a-Amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are implicated in the pathology of neurological diseases such as epilepsy and schizophrenia. As pan antagonists for this target are often accompanied with undesired effects at high doses, one of the recent drug discovery approaches has shifted to subtype-selective AMPA receptor (AMPAR) antagonists, specifically, via modulating transmembrane AMPAR regulatory proteins (TARPs). The quantification of AMPARs by positron emission tomography (PET) would help obtain insights into disease conditions in the living brain and advance the translational development of AMPAR antagonists. Herein we report the design, synthesis and preclinical evaluation of a series of TARP γ-8 antagonists, amenable for radiolabeling, for the development of subtype-selective AMPAR PET imaging agents. Based on the pharmacology evaluation, molecular docking studies and physiochemical properties, we have identified several promising lead compounds 3, 17-19 and 21 for in vivo PET studies. All candidate compounds were labeled with [11C]COCl2 in high radiochemical yields (13-31% RCY) and high molar activities (35-196 GBq/µmol). While tracers 30 ([11C]17) &32 ([11C]21) crossed the blood-brain barrier and showed heterogeneous distribution in PET studies, consistent with TARP γ-8 expression, high nonspecific binding prevented further evaluation. To our delight, tracer 31 ([11C]3) showed good in vitro specific binding and characteristic high uptake in the hippocampus in rat brain tissues, which provides the guideline for further development of a new generation subtype selective TARP γ-8 dependent AMPAR tracers.


Assuntos
Imagem Molecular/métodos , Sondas Moleculares/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Receptores de AMPA/antagonistas & inibidores , Receptores de AMPA/metabolismo , Radioisótopos de Carbono , Relação Dose-Resposta a Droga , Humanos , Imidazóis/síntese química , Imidazóis/química , Sondas Moleculares/síntese química , Sondas Moleculares/química , Estrutura Molecular , Relação Estrutura-Atividade
7.
J Med Chem ; 61(6): 2278-2291, 2018 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-29481079

RESUMO

Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including 11C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [11C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold.


Assuntos
Azetidinas/síntese química , Monoacilglicerol Lipases/antagonistas & inibidores , Monoacilglicerol Lipases/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/síntese química , Animais , Azetidinas/farmacocinética , Encéfalo/diagnóstico por imagem , Encéfalo/enzimologia , Encéfalo/metabolismo , Radioisótopos de Carbono , Radioisótopos de Flúor , Macaca mulatta , Masculino , Camundongos , Traçadores Radioativos , Compostos Radiofarmacêuticos/farmacocinética , Ratos , Ratos Sprague-Dawley , Especificidade por Substrato , Distribuição Tecidual
8.
Nat Chem ; 10(2): 165-169, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29359746

RESUMO

Cyclic amines are ubiquitous core structures of bioactive natural products and pharmaceutical drugs. Although the site-selective abstraction of C-H bonds is an attractive strategy for preparing valuable functionalized amines from their readily available parent heterocycles, this approach has largely been limited to substrates that require protection of the amine nitrogen atom. In addition, most methods rely on transition metals and are incompatible with the presence of amine N-H bonds. Here we introduce a protecting-group-free approach for the α-functionalization of cyclic secondary amines. An operationally simple one-pot procedure generates products via a process that involves intermolecular hydride transfer to generate an imine intermediate that is subsequently captured by a nucleophile, such as an alkyl or aryl lithium compound. Reactions are regioselective and stereospecific and enable the rapid preparation of bioactive amines, as exemplified by the facile synthesis of anabasine and (-)-solenopsin A.


Assuntos
Alcaloides/síntese química , Aminas/química , Aminas/síntese química , Anabasina/síntese química , Alcaloides/química , Anabasina/química , Técnicas de Química Sintética , Estrutura Molecular , Estereoisomerismo
9.
Chemistry ; 23(62): 15553-15577, 2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-28704575

RESUMO

Positron emission tomography (PET) imaging study of fluorine-18 labeled biomolecules is an emerging and rapidly growing area for preclinical and clinical research. The present review focuses on recent advances in radiochemical methods for incorporating fluorine-18 into biomolecules via "direct" or "indirect" bioconjugation. Recently developed prosthetic groups and pre-targeting strategies, as well as representative examples in 18 F-labeling of biomolecules in PET imaging research studies are highlighted.


Assuntos
Marcação por Isótopo/métodos , Nucleotídeos/química , Peptídeos/química , Tomografia por Emissão de Pósitrons , Reação de Cicloadição , Radioisótopos de Flúor/química , Humanos , Compostos Radiofarmacêuticos/química , Compostos de Sulfidrila/química
10.
Chem Commun (Camb) ; 53(49): 6597-6600, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28580477

RESUMO

A copper-mediated 11C-cyanation method employing arylboronic acids and [11C]HCN has been developed. This method was applied to the radiochemical synthesis of a wide range of aromatic 11C-nitriles in aqueous solutions. The use of readily accessible arylboronic acids as precursors makes this method complementary to the well-established 11C-cyanation methods that utilize aryl halide precursors.

11.
ACS Chem Neurosci ; 8(9): 1937-1948, 2017 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-28565908

RESUMO

Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of substance abuse, depression, schizophrenia, and dementias. While quantification of mGlu2 receptors in the living brain by positron emission tomography (PET) would help us better understand signaling pathways relevant to these conditions, few successful examples have been demonstrated to image mGlu2 in vivo, and a suitable PET tracer is yet to be identified. Herein we report the design and synthesis of a radiolabeled negative allosteric modulator (NAM) for mGlu2 PET tracer development based on a quinoline 2-carboxamide scaffold. The most promising candidate, 7-((2,5-dioxopyrrolidin-1-yl)methyl)-4-(2-fluoro-4-[11C]methoxyphenyl) quinoline-2-carboxamide ([11C]QCA) was prepared in 13% radiochemical yield (non-decay-corrected at the end of synthesis) with >99% radiochemical purity and >74 GBq/µmol (2 Ci/µmol) specific activity. While the tracer showed limited brain uptake (0.3 SUV), probably attributable to effects on PgP/Bcrp efflux pump, in vitro autoradiography studies demonstrated heterogeneous brain distribution and specific binding. Thus, [11C]QCA is a chemical probe that provides the basis for the development of a new generation mGlu2 PET tracers.


Assuntos
Encéfalo/metabolismo , Tomografia por Emissão de Pósitrons , Pirrolidinas , Quinolinas , Compostos Radiofarmacêuticos , Receptores de Glutamato Metabotrópico/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/deficiência , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Adesinas de Escherichia coli , Regulação Alostérica , Animais , Autorradiografia , Encéfalo/diagnóstico por imagem , Desenho de Fármacos , Humanos , Imageamento por Ressonância Magnética , Masculino , Camundongos Knockout , Camundongos Mutantes , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Dados Preliminares , Pirrolidinas/química , Quinolinas/química , Compostos Radiofarmacêuticos/síntese química , Ratos Sprague-Dawley , Distribuição Tecidual
12.
Angew Chem Int Ed Engl ; 56(12): 3196-3200, 2017 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-28194833

RESUMO

Trifluoromethylthiolation by sulfuration of difluorocarbene with elemental sulfur is described for the first time, which overrides long-standing trifluoromethyl anion-based theory. Mechanistic elucidation reveals an unprecedented chemical process for the formation of thiocarbonyl fluoride and also enables transition-metal-mediated trifluoromethylthiolation and [18 F]trifluoromethylthiolation of α-bromo carbonyl compounds with broad substrate scope and compatibility.

13.
Heart Lung Circ ; 26(5): 509-518, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27771236

RESUMO

BACKGROUND: This study aimed to investigate the effect of bone marrow derived mesenchymal stem cells (rBMSCs) transduced with lentiviral vectors expressing endothelial nitric oxide synthase (eNOS) and/or a mutant caveolin-1(F92A-Cav1), on the pulmonary haemodynamics and structure in a rat model of pulmonary arterial hypertension (PAH). METHODS: Pulmonary arterial hypertension was induced with monocrotaline (MCT) in 60 adult male Wistar rats prior to delivery of lentiviral vector transduced rBMSCs expressing Cav1, eNOS and/or F92A-Cav1. Changes in pulmonary haemodynamics, right ventricular hypertrophy index (RVHI), and serum nitric oxide (NO) were evaluated. Ultrastructure changes in lung tissues were observed by transmission electron microscopy. Expression of Kruppel-like factor 4 (KLF4), p53, P21, eNOS, and alpha-smooth muscle actin were evaluated by real time PCR, western blotting or immunohistochemistry. RESULTS: Treatment of PAH rats with gene modified rBMSCs (eNOS +/- Cav1 F92A) decreased right ventricular systolic pressure and improved pulmonary haemodynamics. The protein of alpha-smooth muscle actin expression was decreased whilst KLF4, p53, P21, eNOS expression, and serum NO concentration was elevated. The survival rate of rats in the treatment groups was also improved, after 35 days of observation. CONCLUSION: Intravenous delivery of rBMSCs expressing eNOS/F92A-Cav1 to PAH rats inhibits pulmonary vascular smooth muscle cell proliferation, and improves pulmonary haemodynamics, vascular remodelling and short-term survival. Activation of KLF4-p53 signalling pathway may be involved in these beneficial effects.


Assuntos
Caveolina 1/biossíntese , Proliferação de Células , Regulação da Expressão Gênica , Hipertensão Pulmonar , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Músculo Liso Vascular/metabolismo , Mutação de Sentido Incorreto , Miócitos de Músculo Liso/metabolismo , Óxido Nítrico Sintase Tipo III/biossíntese , Aloenxertos , Substituição de Aminoácidos , Animais , Caveolina 1/genética , Modelos Animais de Doenças , Humanos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/terapia , Fator 4 Semelhante a Kruppel , Masculino , Óxido Nítrico Sintase Tipo III/genética , Ratos , Ratos Wistar , Transdução Genética
14.
Chemistry ; 22(50): 18179-18189, 2016 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-27712000

RESUMO

Cyclic amines such as pyrrolidine and piperidine are known to undergo condensations with aldehydes to furnish pyrrole and pyridine derivatives, respectively. A combined experimental and computational study provides detailed insights into the mechanism of pyrrole formation. A number of reactive intermediates (e.g., azomethine ylides, conjugated azomethine ylides, enamines) were intercepted, outlining strategies for circumventing aromatization as a valuable pathway for amine C-H functionalization.

15.
Theranostics ; 6(8): 1145-59, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27279908

RESUMO

Monoacylglycerol lipase (MAGL) is a 33 kDa member of the serine hydrolase superfamily that preferentially degrades 2-arachidonoylglycerol (2-AG) to arachidonic acid in the endocannabinoid system. Inhibition of MAGL is not only of interest for probing the cannabinoid pathway but also as a therapeutic and diagnostic target for neuroinflammation. Limited attempts have been made to image MAGL in vivo and a suitable PET ligand for this target has yet to be identified and is urgently sought to guide small molecule drug development in this pathway. Herein we synthesized and evaluated the physiochemical properties of an array of eleven sulfonamido-based carbamates and ureas with a series of terminal aryl moieties, linkers and leaving groups. The most potent compounds were a novel MAGL inhibitor, N-((1-(1H-1,2,4-triazole-1-carbonyl)piperidin-4-yl) methyl)-4-chlorobenzenesulfonamide (TZPU; IC50 = 35.9 nM), and the known inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(((4-chlorophenyl)sulfonamido) methyl)piperidine-1-carboxylate (SAR127303; IC50 = 39.3 nM), which were also shown to be selective for MAGL over fatty acid amide hydrolase (FAAH), and cannabinoid receptors (CB1 & CB2). Both of these compounds were radiolabeled with carbon-11 via [(11)C]COCl2, followed by comprehensive ex vivo biodistribution and in vivo PET imaging studies in normal rats to determine their brain permeability, specificity, clearance and metabolism. Whereas TZPU did not show adequate specificity to warrant further evaluation, [(11)C]SAR127303 was advanced for preliminary PET neuroimaging studies in nonhuman primate. The tracer showed good brain permeability (ca. 1 SUV) and heterogeneous regional brain distribution which is consistent with the distribution of MAGL.


Assuntos
Carbamatos/metabolismo , Radioisótopos de Carbono/metabolismo , Monoacilglicerol Lipases/análise , Neuroimagem/métodos , Tomografia por Emissão de Pósitrons/métodos , Sulfonamidas/metabolismo , Ureia/metabolismo , Animais , Carbamatos/síntese química , Carbamatos/farmacocinética , Radioisótopos de Carbono/farmacocinética , Ratos , Sulfonamidas/síntese química , Sulfonamidas/farmacocinética , Ureia/síntese química , Ureia/farmacocinética
16.
Biomed Pharmacother ; 77: 7-13, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26796258

RESUMO

BACKGROUND: Nitric oxide (NO) is generated in endothelial cells by endothelial nitric oxide synthase (eNOS). Caveolin-1 (Cav1) inhibits eNOS function and NO production. Modifying Cav1 scaffold domain, in particular Phenylalanine at position 92 (F92) is critical for the inhibitory actions of Cav1 toward eNOS. The aims of this study were to investigate the effect of enhanced NO production in term of in vitro angiogenesis on rat bone marrow derived mesenchymal stem cells (BMSCs) transduced with a novel bicistronic lentiviral vector co-expressing eNOS and mutant Cav1 (F92A). METHODS: A bicistronic eNOS/F92-Cav1 lentiviral vector was constructed, and used to transduce rat BMSCs. The expression of eNOS and VEGF protein were confirmed by western-blot. NO production was detected by the greiss assay and in vitro angiogenesis was assessed by matrigel assisted capillary tube formation. The cell viability was evaluated using a Cell Counting Kit (CCK)-8. RESULTS: The bicistronic eNOS/F92A-Cav1 lentiviral vector increased eNOS and VEGF protein expression, NO production compared to controls. In vitro capillary formation was increased in eNOS-F92A transduced cells and cell viability was not affected by transduction. CONCLUSION: Transduction of rat BMSCs with an eNOS-F92A-Cav1 lentiviral vector can increase NO production by enhancing eNOS protein expression. The increased NO production did not reduce cell viability. This study demonstrates that genetic modification of BMSCs to enhance NO producton could be applied in stem cell based therapeutic approaches to treat diseases such as pulmonary arterial hypertension (PAH) which is characterized by decreased endothelial NO release.


Assuntos
Caveolina 1/genética , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico/biossíntese , Animais , Sobrevivência Celular , Células Cultivadas , Citometria de Fluxo , Vetores Genéticos , Glicocálix , Lentivirus , Polimorfismo de Nucleotídeo Único , Ratos , Transdução Genética
17.
Chemistry ; 21(37): 12908-13, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26220197

RESUMO

Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-CH bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies.


Assuntos
Aminas/química , Alcaloides de Berberina/síntese química , Pirrolidinas/química , Alcaloides de Berberina/química , Catálise , Ciclização , Estrutura Molecular , Oxirredução
18.
Artigo em Inglês | MEDLINE | ID: mdl-24441293

RESUMO

AIMS: This study was designed to investigate the predictive value of serum collagen biomarkers on the outcomes of acute ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI). METHODS: Two hundred and ten patients with STEMI were successfully treated with PCI within 6 hrs ofthe onset of chest pain. The levels of serum procollagen type I carboxyterminal peptide (PICP) and procollagen type III peptide (PIIINP) were measured by enzymelinked immunosorbent assay (ELISA) before, 3 and 6 months after PCI. Left ventricular ejection fraction was assessed by echocardiography at 3 and 6 months after PCI. The composite endpoints were death by any cause, recurrent myocardial infarction, heart failure or stroke. RESULTS: At the end of the 12-month follow up, 29 patients (13.8%) experienced an end point. The level of serum PICP in patients with an end point was higher than in patients without an end point 7 days (19.45 ± 2.17 vs 14.95 ± 3.07 ng/mL, P<0.05) or 3 month after the PCI (29.87 ± 3.02 vs 22.14 ± 3.33 ng/mL, P<0.05). The serum PIIINP level in patients with an end point was also higher than those without 7 days after PCI (59.34 ± 4.23 vs 48.78 ± 4.23 ng/mL, P<0.05). Multivariate logistic regression analysis showed day 7 (OR=2.170, 95% CI 1.583-4.345, P=0.01) and 3-month serum PICP (OR=2.340, 95% CI 1.431-4.650, P=0.01) were independent predictors of composite end points. CONCLUSIONS: Persistent elevation of serum collagen marker PICP three months after PCI predicts an adverse outcome for patients with acute ST-elevation myocardial infarction.


Assuntos
Infarto do Miocárdio/terapia , Fragmentos de Peptídeos/metabolismo , Intervenção Coronária Percutânea , Pró-Colágeno/metabolismo , Análise de Variância , Biomarcadores/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Recidiva , Volume Sistólico/fisiologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/etiologia
19.
Clin Exp Hypertens ; 36(1): 27-31, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23638647

RESUMO

OBJECTIVE: To investigate the association between anxiety disorders and left ventricular hypertrophy in patients with essential hypertension. METHODS: Left ventricular structure and function were assessed with echocardiography in 56 patients with essential hypertension and anxiety disorder (study group) and in 56 patients with hypertension only (control group). Serum adrenomedullin levels were also measured in these patients. RESULTS: There was no statistically significant difference in the left ventricular ejection fraction between the study and the control group (54.21 ± 88.81% versus 56.01 ± 7.85%, p>0.05). The left ventricular mass index (LVMI) in study group was higher than in control group (137.05 ± 9.42 versus 123.57 ± 7.01 g/m(2), p=0.001). The plasma levels of adrenomedullin in study group was higher than in control group (25.97 ± 5.48 versus 18.32 ± 6.97 ng/L, p=0.001). Levels of plasma adrenomedullin were positively correlated with LVMI in the study (r=0.734, p<0.05) and control group (r=0.592, p<0.05). CONCLUSION: Anxiety disorders are associated with elevated plasma adrenomedullin levels and increased left ventricular hypertrophy in patients with essential hypertension. The clinical significance of these changes requires further investigation.


Assuntos
Adrenomedulina/sangue , Transtornos de Ansiedade/sangue , Transtornos de Ansiedade/complicações , Hipertensão/sangue , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/complicações , Adulto , Idoso , Estudos de Casos e Controles , Hipertensão Essencial , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Ultrassonografia , Função Ventricular Esquerda , Adulto Jovem
20.
Exp Clin Cardiol ; 18(1): 13-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24294030

RESUMO

BACKGROUND: Intravenous infusion of prostaglandin E1 (PGE1) has been used to treat pulmonary arterial hypertension (PAH); however, the efficacy and safety of inhaled PGE1 is unclear. OBJECTIVES: To investigate the effect of inhaled PGE1 on PAH following corrective surgery for congenital heart disease. METHODS: Sixty patients with postoperative residual PAH following corrective surgery for congenital heart disease were randomly assigned to a control group, a PGE1 infusion group (intravenous PGE1 infusion; 30 ng/kg/min daily for 10 days) or a PGE1 inhalation group (100 µg nebulized PGE1 every 8 h for 10 days). Systolic blood pressure, mean pulmonary arterial pressure, arterial oxygen pressure, oxygen saturation and serum endothelin-1 level were measured before and after the treatment. RESULTS: At the end of the study, the mean pulmonary arterial pressure in the two PGE1 groups were lower than in the control group (P<0.01), whereas the mean arterial oxygen pressure was higher (P<0.01). Compared with the PGE1 infusion group, the mean pulmonary arterial pressure in the PGE1 inhalation group was lower (P<0.01) whereas the arterial oxygen pressure was higher (P<0.01). The mean endothelin-1 levels in the two PGE1 groups were lower than in the control group (P<0.01), but there was no statistically significant difference in endothelin-1 levels between the PGE1 inhalation and infusion groups (P>0.05). CONCLUSIONS: In pediatric patients with PAH, PGE1 inhalation was associated with a reduction in pulmonary arterial pressure and improvement in arterial blood oxygen levels.

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