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[PMID]:28452905
[Au] Autor:Regidor I; Benita V; Del Álamo de Pedro M; Ley L; Martinez Castrillo JC
[Ad] Endereço:*Unit of Functional Neurosurgery, †Service of Neurophysiology, ‡Service of Gastroenterology, §Service of Neurosurgery, and ∥Service of Neurology, Hospital Universitario Ramón y Cajal, Madrid, Spain.
[Ti] Título:Duodenal Levodopa Infusion for Long-Term Deep Brain Stimulation-Refractory Symptoms in Advanced Parkinson Disease.
[So] Source:Clin Neuropharmacol;40(3):103-107, 2017 May/Jun.
[Is] ISSN:1537-162X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: This study assesses the effect of levodopa/carbidopa intestinal infusion gel (LCIIG) as an additional treatment in patients with advanced idiopathic Parkinson disease (PD) previously treated with deep brain stimulation (DBS). METHODS: Prospective study of advanced PD patients, satisfactorily treated with bilateral DBS of the subthalamic nucleus, who had developed refractory symptoms and LCIIG was added. Controls were advanced PD patients treated with LCIIG. Measurements included the Unified Parkinson Disease Rating Scale (UPDRS)-III and the UPDRS axial compound. RESULTS: There were 19 patients in the DBS-LCIIG therapy group and 21 in the control group. The DBS-LCIIG patients were younger and had disease duration longer than controls. The median time from DBS to gastrostomy was 7.8 years (range, 2-12 years). In both study groups, the mean scores of the UPDRS-III and UPDRS axial subscales improved significantly after LCIIG treatment (DBS-LCIIG group: UPDRS-III, 62.0 [15.7] vs 30.9 [12.1]; UPDRS axial, 24.7 [4.9] vs 10.2 [2.7]; P < 0.0005 for all comparisons). There were no differences in adverse events between the groups. In the follow-up of the DBS-LCIIG group. 5 patients discontinued DBS-LCIIG therapy and returned to DBS, 5 discontinued DBS and were maintained with LCIIG, and the remaining 9 continued with DBS-LCIIG therapy. Mean time until discontinuation in the double DBS-LCIIG group was 891 days. The main risk factors for discontinuation were age at the beginning of LCIIG and severity of the UPDRS axial subscale. CONCLUSIONS: Levodopa/carbidopa intestinal infusion gel therapy may be a valuable option in selected patients with advanced PD who develop refractory symptoms after long-term subthalamic nucleus-DBS.
[Mh] Termos MeSH primário: Antiparkinsonianos/administração & dosagem
Carbidopa/administração & dosagem
Estimulação Encefálica Profunda
Gastrostomia
Levodopa/administração & dosagem
Doença de Parkinson/tratamento farmacológico
Doença de Parkinson/terapia
Aceitação pelo Paciente de Cuidados de Saúde
[Mh] Termos MeSH secundário: Fatores Etários
Idoso
Antiparkinsonianos/efeitos adversos
Antiparkinsonianos/uso terapêutico
Carbidopa/efeitos adversos
Carbidopa/uso terapêutico
Terapia Combinada/efeitos adversos
Estimulação Encefálica Profunda/efeitos adversos
Combinação de Medicamentos
Duodeno
Feminino
Seguimentos
Gastrostomia/efeitos adversos
Géis
Seres Humanos
Intubação Gastrointestinal
Levodopa/efeitos adversos
Levodopa/uso terapêutico
Masculino
Meia-Idade
Doença de Parkinson/fisiopatologia
Pacientes Desistentes do Tratamento
Estudos Prospectivos
Índice de Gravidade de Doença
Espanha
Núcleo Subtalâmico
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Drug Combinations); 0 (Gels); 0 (carbidopa, levodopa drug combination); 46627O600J (Levodopa); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1097/WNF.0000000000000216


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[PMID]:29241898
[Au] Autor:Marshall T; Pugh A; Fairchild A; Hass S
[Ad] Endereço:AbbVie, Inc., North Chicago, IL, USA. Electronic address: t.marshall@abbvie.com.
[Ti] Título:Patient Preferences for Device-Aided Treatments Indicated for Advanced Parkinson Disease.
[So] Source:Value Health;20(10):1383-1393, 2017 12.
[Is] ISSN:1524-4733
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Effective treatment for advanced Parkinson disease (PD) uncontrolled with oral medication includes device-aided therapies such as deep brain stimulation (DBS) and continuous levodopa-carbidopa infusion to the duodenum via a portable pump. OBJECTIVE: Our objective was to quantify patient preferences for attributes of these device-aided treatments. METHODS: We administered a Web-enabled survey to 401 patients in the United States. A discrete-choice experiment (DCE) was used to evaluate patients' willingness to accept tradeoffs among efficacy, tolerability, and convenience of alternative treatments. DCE data were analyzed using random-parameters logit. Best-worst scaling (BWS) was used to elicit the relative importance of device-specific attributes. Conditional logit was used to analyze the BWS data. We tested for differences in preferences among subgroups of patients. RESULTS: Improving ability to think clearly was twice as important as a 6-hour-per-day improvement in control of movement symptoms. After controlling for efficacy, treatment delivered via portable infusion pump was preferred over DBS, and both devices were preferred to oral therapy with poor symptom control. Patients were most concerned about device attributes relating to risk of stroke, difficulty thinking, and neurosurgery. Avoiding surgery to insert a wire in the brain was more important than avoiding surgery to insert a tube into the small intestine. Some differences in preferences among subgroups were statistically, but not qualitatively, significant. CONCLUSIONS: This study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions.
[Mh] Termos MeSH primário: Antiparkinsonianos/administração & dosagem
Carbidopa/administração & dosagem
Estimulação Encefálica Profunda/métodos
Levodopa/administração & dosagem
Doença de Parkinson/terapia
Preferência do Paciente
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Comportamento de Escolha
Combinação de Medicamentos
Sistemas de Liberação de Medicamentos
Duodeno
Desenho de Equipamento
Feminino
Seres Humanos
Bombas de Infusão
Internet
Masculino
Meia-Idade
Doença de Parkinson/fisiopatologia
Doença de Parkinson/psicologia
Inquéritos e Questionários
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Drug Combinations); 0 (carbidopa, levodopa drug combination); 46627O600J (Levodopa); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE


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[PMID]:29277794
[Au] Autor:Nakuz TS; Berger E; El-Rabadi K; Wadsak W; Haug A; Hacker M; Karanikas G
[Ad] Endereço:Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.
[Ti] Título:Clinical Value of F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma.
[So] Source:Anticancer Res;38(1):353-358, 2018 01.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:AIM: We evaluated the clinical usefulness of 6-[ F]fluoro-3,4-dihydroxy-L-phenylalanine( F-FDOPA)-positron-emission tomography (PET)/computed tomography (CT) in insulinoma detection with contrast enhancement, early acquisition time, and no carbidopa premedication. PATIENTS AND METHODS: Twenty-six patients diagnosed with hyperinsulinemic hypoglycemia underwent an F-FDOPA PET/CT examination. Patients without carbidopa premedication and contrast-enhanced CT were included. Imaging findings were compared to the overall final diagnosis (histological findings). RESULTS: In 10 of 26 patients (eight women, two men; mean age=53 years; age range=30-94 years), a detected lesion was confirmed histologically as an insulinoma. F-FDOPA PET detected the tumor in five out of ten patients. Contrast-enhanced CT also detected the tumor in five out of ten. Overall, F-FDOPA PET/CT, with contrast enhancement and without carbidopa premedication, was able to detect the insulinoma in seven out of ten patients (70%). CONCLUSION: Based on our data, F-DOPA PET/CT, with contrast enhancement and without carbidopa premedication, as a 'one-stop' diagnostic modality is a viable option for insulinoma detection.
[Mh] Termos MeSH primário: Inibidores das Descarboxilases de Aminoácidos Aromáticos/farmacologia
Carbidopa/farmacologia
Di-Hidroxifenilalanina/análogos & derivados
Insulinoma/diagnóstico por imagem
Insulinoma/diagnóstico
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Di-Hidroxifenilalanina/farmacologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Pré-Medicação
Compostos Radiofarmacêuticos/farmacologia
Estudos Retrospectivos
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aromatic Amino Acid Decarboxylase Inhibitors); 0 (Radiopharmaceuticals); 2C598205QX (fluorodopa F 18); 63-84-3 (Dihydroxyphenylalanine); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180104
[Lr] Data última revisão:
180104
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171227
[St] Status:MEDLINE


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[PMID]:29236641
[Au] Autor:Eichler FS; Swoboda KJ; Hunt AL; Cestari DM; Rapalino O
[Ad] Endereço:From the Departments of Neurology (F.S.E., K.J.S., A.L.H.) and Radiology (O.R.), Massachusetts General Hospital, the Departments of Neurology (F.S.E., K.J.S., A.L.H.), Ophthalmology (D.M.C.), and Radiology (O.R.), Harvard Medical School, and the Department of Ophthalmology, Massachusetts Eye and Ear
[Ti] Título:Case 38-2017. A 20-Year-Old Woman with Seizures and Progressive Dystonia.
[So] Source:N Engl J Med;377(24):2376-2385, 2017 Dec 14.
[Is] ISSN:1533-4406
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doenças dos Gânglios da Base/diagnóstico
Distonia/etiologia
Proteínas de Membrana Transportadoras/genética
Mutação
Convulsões/etiologia
[Mh] Termos MeSH secundário: Doenças dos Gânglios da Base/complicações
Doenças dos Gânglios da Base/tratamento farmacológico
Doenças dos Gânglios da Base/genética
Biotina/uso terapêutico
Encéfalo/diagnóstico por imagem
Carbidopa/uso terapêutico
Diagnóstico Diferencial
Combinação de Medicamentos
Distonia/tratamento farmacológico
Feminino
Seres Humanos
Levodopa/uso terapêutico
Macula Lutea/patologia
Imagem por Ressonância Magnética
Erros Inatos do Metabolismo/diagnóstico
Nervo Óptico/patologia
Tiamina/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:CASE REPORTS; CLINICAL CONFERENCE; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drug Combinations); 0 (Membrane Transport Proteins); 0 (SLC19A3 protein, human); 0 (carbidopa, levodopa drug combination); 46627O600J (Levodopa); 6SO6U10H04 (Biotin); MNX7R8C5VO (Carbidopa); X66NSO3N35 (Thiamine)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE
[do] DOI:10.1056/NEJMcpc1706109


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[PMID]:28468476
[Au] Autor:Ezat B; Pihlstrøm L; Aasly J; Tysnes OB; Egge A; Dietrichs E
[Ad] Endereço:Nevrologisk avdeling Oslo universitetssykehus og Det medisinske fakultet Universitetet i Oslo.
[Ti] Título:Use of advanced therapies for Parkinson's disease in Norway.
[Ti] Título:Bruk av avansert behandling ved Parkinsons sykdom i Norge..
[So] Source:Tidsskr Nor Laegeforen;137(9):619-623, 2017 05.
[Is] ISSN:0807-7096
[Cp] País de publicação:Norway
[La] Idioma:eng; nor
[Ab] Resumo:BACKGROUND: Many patients with Parkinson's disease with severe motor fluctuations benefit from advanced therapies ­ either deep brain stimulation or continuous infusion therapy with levodopa-carbidopa intestinal gel or apomorphine. In Norway, deep brain stimulation is provided as a shared national or multi-regional service. The treatment is currently available at Oslo University Hospital and St. Olavs Hospital; prior to 2012 it was also available at Haukeland University Hospital. Infusion therapy has no similar geographical restrictions. We therefore wished to examine geographical differences in the use of the two most common forms of advanced therapy for Parkinson's disease. MATERIAL AND METHOD: The county of residence of all patients receiving deep brain stimulation or infusion therapy with levodopa-carbidopa intestinal gel in the period 2009 ­ 2013 was recorded using data from hospital episode statistics and the Norwegian Prescription Database, respectively. RESULTS: A total of 262 patients with Parkinson's disease began advanced therapy, 146 with deep brain stimulation and 116 with levodopa-carbidopa infusion. Four counties differed significantly from the others in their use of the two methods. Møre og Romsdal, Nordland and Sør-Trøndelag treated a significantly greater proportion of patients with deep brain stimulation, while Rogaland treated a significantly greater proportion with levodopa-carbidopa infusion therapy. INTERPRETATION: Advanced therapies for Parkinson's disease are offered throughout Norway, but there are significant geographical differences in the type of therapy initiated. One possible explanation is that patients in different counties receive different information about the therapeutic options available.
[Mh] Termos MeSH primário: Antiparkinsonianos
Estimulação Encefálica Profunda/estatística & dados numéricos
Uso de Medicamentos
Disparidades em Assistência à Saúde
Doença de Parkinson
[Mh] Termos MeSH secundário: Antiparkinsonianos/administração & dosagem
Antiparkinsonianos/uso terapêutico
Apomorfina/administração & dosagem
Apomorfina/uso terapêutico
Carbidopa/administração & dosagem
Carbidopa/uso terapêutico
Combinação de Medicamentos
Géis
Seres Humanos
Infusões Parenterais
Levodopa/administração & dosagem
Levodopa/uso terapêutico
Noruega/epidemiologia
Doença de Parkinson/tratamento farmacológico
Doença de Parkinson/epidemiologia
Doença de Parkinson/terapia
Educação de Pacientes como Assunto/normas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Drug Combinations); 0 (Gels); 0 (carbidopa, levodopa drug combination); 46627O600J (Levodopa); MNX7R8C5VO (Carbidopa); N21FAR7B4S (Apomorphine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4045/tidsskr.16.0711


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[PMID]:28963435
[Au] Autor:Ogura J; Miyauchi S; Shimono K; Yang S; Gonchigar S; Ganapathy V; Bhutia YD
[Ad] Endereço:Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, U.S.A.
[Ti] Título:Carbidopa is an activator of aryl hydrocarbon receptor with potential for cancer therapy.
[So] Source:Biochem J;474(20):3391-3402, 2017 Sep 28.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both and Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect. The inhibitory effect was confirmed using human recombinant IDO1. To demonstrate the inhibition in intact cells, AhR (aryl hydrocarbon receptor) activity was monitored as readout for IDO1-mediated generation of the endogenous AhR agonist kynurenine in pancreatic and liver cancer cells. Surprisingly, Carbidopa did not inhibit but instead potentiated AhR signaling, evident from increased CYP1A1 (cytochrome P450 family 1 subfamily A member 1), CYP1A2, and CYP1B1 expression. In pancreatic and liver cancer cells, Carbidopa promoted AhR nuclear localization. AhR antagonists blocked Carbidopa-dependent activation of AhR signaling. The inhibitory effect on pancreatic cancer cells and and the activation of AhR occurred at therapeutic concentrations of Carbidopa. Chromatin immunoprecipitation assay further confirmed that Carbidopa promoted AhR binding to its target gene CYP1A1 leading to its induction. We conclude that Carbidopa is an AhR agonist and suppresses pancreatic cancer. Hence, Carbidopa could potentially be re-purposed to treat pancreatic cancer and possibly other cancers as well.
[Mh] Termos MeSH primário: Carbidopa
Núcleo Celular
Proteínas de Neoplasias
Neoplasias Pancreáticas
Receptores de Hidrocarboneto Arílico
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Transporte Ativo do Núcleo Celular/efeitos dos fármacos
Hidrocarboneto de Aril Hidroxilases/genética
Hidrocarboneto de Aril Hidroxilases/metabolismo
Carbidopa/farmacocinética
Carbidopa/farmacologia
Núcleo Celular/genética
Núcleo Celular/metabolismo
Células Hep G2
Seres Humanos
Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores
Indolamina-Pirrol 2,3,-Dioxigenase/genética
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo
Cinurenina/metabolismo
Neoplasias Hepáticas/tratamento farmacológico
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Proteínas de Neoplasias/agonistas
Proteínas de Neoplasias/genética
Proteínas de Neoplasias/metabolismo
Neoplasias Pancreáticas/tratamento farmacológico
Neoplasias Pancreáticas/genética
Neoplasias Pancreáticas/metabolismo
Receptores de Hidrocarboneto Arílico/agonistas
Receptores de Hidrocarboneto Arílico/genética
Receptores de Hidrocarboneto Arílico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Indoleamine-Pyrrole 2,3,-Dioxygenase); 0 (Neoplasm Proteins); 0 (Receptors, Aryl Hydrocarbon); 0 (indoleamine 2,3-dioxygenase 1, human); 343-65-7 (Kynurenine); EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170583


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[PMID]:28915419
[Au] Autor:van de Merbel NC; Bronsema KJ; Gorman SH; Bakhtiar R
[Ad] Endereço:Bioanalytical Laboratory, PRA Health Sciences, Amerikaweg 18, 9407 TK, Assen, The Netherlands; Analytical Biochemistry, Department of Pharmacy, University of Groningen, A. Deusinglaan 1, 9700 AV, Groningen, The Netherlands. Electronic address: merbelnicovande@prahs.com.
[Ti] Título:Sensitivity improvement of the LC-MS/MS quantification of carbidopa in human plasma and urine by derivatization with 2,4-pentanedione.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1064:62-67, 2017 Oct 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The reliable quantification of carbidopa in biological samples at low concentrations is challenging because of the polar and highly unstable nature of the compound. In this paper, LC-MS/MS methods are described for the determination of carbidopa in 50µL of human plasma and 25µL of human urine in the concentration ranges 1-1,000ng/mL and 100-50,000ng/mL, respectively. After a simple protein precipitation (plasma) or dilution (urine) step, carbidopa is derivatized at its hydrazine moiety by reaction for one hour with 2,4-pentanedione under acidic conditions and at 40°C. The product is a relatively non-polar molecule that is suitable for reversed-phase liquid chromatography (3.5min run time) with detection by tandem mass spectrometry with electrospray ionization. A stable-isotope labeled internal standard is used for response normalization. Precision, accuracy and selectivity of the methods meet the criteria of international guidelines for bioanalytical method validation. Acidification of urine to pH 1.5 and the addition of two anti-oxidants (5mg/mL sodium metabisulfite and 1mg/mL butylated hydroxytoluene) to plasma, in combination with sampling and analysis on ice and under yellow light, ensure sufficient stability of carbidopa. The methods were successfully used to determine plasma pharmacokinetics and urinary excretion of carbidopa in healthy volunteers after a single 37.5mg oral dose.
[Mh] Termos MeSH primário: Carbidopa/sangue
Carbidopa/urina
Cromatografia Líquida/métodos
Pentanonas/química
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Carbidopa/farmacocinética
Seres Humanos
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Pentanones); 46R950BP4J (acetylacetone); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE


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[PMID]:28898256
[Au] Autor:Zhu H; Lemos H; Bhatt B; Islam BN; Singh A; Gurav A; Huang L; Browning DD; Mellor A; Fulzele S; Singh N
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, Georgia, United States of America.
[Ti] Título:Carbidopa, a drug in use for management of Parkinson disease inhibits T cell activation and autoimmunity.
[So] Source:PLoS One;12(9):e0183484, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson's Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS. However, the effect of carbidopa on T cell responses in vivo is unknown. In this report, we show that carbidopa strongly inhibited T cell activation in vitro and in vivo. Accordingly, carbidopa mitigated myelin oligodendrocyte glycoprotein peptide fragment 35-55 (MOG-35-55) induced experimental autoimmune encephalitis (EAE) and collagen induced arthritis in animal models. The data presented here suggest that in addition to blocking peripheral conversion of levodopa, carbidopa may inhibit T cell responses in PD individuals and implicate a potential therapeutic use of carbidopa in suppression of T cell mediated pathologies.
[Mh] Termos MeSH primário: Antiparkinsonianos/farmacologia
Autoimunidade/efeitos dos fármacos
Carbidopa/farmacologia
Dopaminérgicos/farmacologia
Ativação Linfocitária/efeitos dos fármacos
Linfócitos T/efeitos dos fármacos
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Artrite Experimental/tratamento farmacológico
Artrite Experimental/imunologia
Artrite Experimental/metabolismo
Artrite Experimental/patologia
Doenças Autoimunes/imunologia
Doenças Autoimunes/metabolismo
Citocinas/metabolismo
Modelos Animais de Doenças
Encefalomielite Autoimune Experimental/tratamento farmacológico
Encefalomielite Autoimune Experimental/imunologia
Encefalomielite Autoimune Experimental/metabolismo
Mediadores da Inflamação/metabolismo
Ativação Linfocitária/imunologia
Contagem de Linfócitos
Macrófagos/efeitos dos fármacos
Macrófagos/imunologia
Macrófagos/metabolismo
Camundongos
Subpopulações de Linfócitos T/efeitos dos fármacos
Subpopulações de Linfócitos T/imunologia
Subpopulações de Linfócitos T/metabolismo
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Cytokines); 0 (Dopamine Agents); 0 (Inflammation Mediators); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171018
[Lr] Data última revisão:
171018
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183484


  9 / 2173 MEDLINE  
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[PMID]:28412665
[Au] Autor:Chi J; Ling Y; Jenkins R; Li F
[Ad] Endereço:PPD Inc., Middleton, WI, United States.
[Ti] Título:Quantitation of levodopa and carbidopa in rat plasma by LC-MS/MS: The key role of ion-pairing reversed-phase chromatography.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1054:1-9, 2017 Jun 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:A simple and selective bioanalytical method was developed for simultaneous determination of levodopa and carbidopa in rat plasma by LC-MS/MS. Levodopa and carbidopa are small polar molecules, posing challenges in the development of selective and efficient chromatography conditions. Perfluoropentanoic acid (PFPA), a volatile ion-pairing agent, was utilized to enhance chromatographic characteristics of both compounds in the reversed-phase mechanism. The ion-pairing chromatography played an essential role in mitigating matrix effects and achieving adequate separation between interfering background peaks and those of the analytes of interest, especially for levodopa. A 96-well based, automated liquid-liquid extraction, via the use Hamilton NIMBUS liquid handlers, was developed. Butyl alcohol, when mixed with ethyl acetate, greatly increased the recovery of both levodopa and carbidopa. The addition of PFPA further enhanced recovery for both analytes. Sodium metabisulfite, an antioxidant, was used to stabilize levodopa and carbidopa in rat plasma. The method was validated in the ranges of 50-10,000ng/mL and 25-5000ng/mL for levodopa and carbidopa, respectively, using levodopa-d3 and carbidopa-d3 as internal standards. The validated method was successfully applied to analyze rat plasma samples from in-life studies.
[Mh] Termos MeSH primário: Carbidopa/sangue
Cromatografia de Fase Reversa/métodos
Dopaminérgicos/sangue
Levodopa/sangue
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Carbidopa/análise
Dopaminérgicos/análise
Levodopa/análise
Limite de Detecção
Extração Líquido-Líquido/métodos
Ácidos Pentanoicos/química
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Dopamine Agents); 0 (Pentanoic Acids); 0 (perfluoropentanoic acid); 46627O600J (Levodopa); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170417
[St] Status:MEDLINE


  10 / 2173 MEDLINE  
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[PMID]:28374689
[Au] Autor:Skoromets AA; Odinak MM; Yakupov EZ; Litvinenko IV; Zalyalova ZA; Timofeeva AA; Kirtaev SY; Bogdanov RR; Agafina AS; Chatamra K; Robieson W; Benesh J; Latypova GR; Ershova MV; Illarioshkin SN
[Ad] Endereço:Pavlov First St.-Petersburg State Medical University, St.-Petersburg.
[Ti] Título:[Levodopa-carbidopa intestinal gel in the treatment of patients with Parkinson disease: results of a 12-month open study].
[Ti] Título:Levodopa-karbidopa intestinal'nyi gel' v terapii bol'nykh s razvernutymi stadiyami bolezni Parkinsona: rezul'taty 12-mesyachnogo otkrytogo issledovaniya..
[So] Source:Zh Nevrol Psikhiatr Im S S Korsakova;117(2):22-31, 2017.
[Is] ISSN:1997-7298
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:AIM: To evaluate the long-term safety and efficacy of intrajejunal levodopa-carbidopa intestinal gel (LCIG) infusion in the treatment of patients with severe stages of Parkinson disease (PD) who did not respond adequately to treatment with oral drugs. MATERIAL AND METHODS: A large-scale international prospective open-label 54-week study of LCIG in patients with PD with severe motor fluctuations was carried out. A total of 48 patients were enrolled in Russia, 46 patients (95.8%) had PEG-J inserted, and 43 of them completed the study. The safety, including adverse events (AEs), infusion system and pump failures analysis, number of patients completely terminated the study, and efficacy (duration of "off" periods, "on" periods with or without troublesome dyskinesias, UPDRS scores, Clinical Global Impression, Quality of Life (PDQ-39, EQ-5D и EQ-VAS) dynamics, an analysis of patient's diaries) were assessed throughout the whole study. RESULTS: The majority of AEs were mild or moderate with most AEs connected with infusion system application (28.3% patients) including procedure pain. Serious AEs were registered in 8 patients (16.7%). 3 patients (6.3%) discontinued their participation in the study due to AEs. Mean duration of "off" periods by the end of the study decreased by 5.35±2.59 hours (p<0.001), duration of "on" periods without troublesome dyskinesia increased by 5.74±3.91 hours (p<0.001), reduction of "on" periods duration with troublesome dyskinesia became statistically significant by week 36 (p=0.020). The statistically significant improvement of UPDRS (generally and in respect to sub-scales), Clinical Global Impression, and Quality of Life scores was observed throughout the study. Levodopa dose remained stable throughout the 54 treatment weeks. Forty-three patients (93.5%) received LCIG monotherapy throughout the whole study. CONCLUSION: LCIG intrajejunal infusion during 54 weeks showed the favorable safety profile, high tolerability, and efficacy in PD motor symptoms correction.
[Mh] Termos MeSH primário: Antiparkinsonianos/efeitos adversos
Carbidopa/efeitos adversos
Levodopa/efeitos adversos
Doença de Parkinson/tratamento farmacológico
[Mh] Termos MeSH secundário: Idoso
Antiparkinsonianos/administração & dosagem
Antiparkinsonianos/uso terapêutico
Carbidopa/administração & dosagem
Carbidopa/uso terapêutico
Combinação de Medicamentos
Discinesia Induzida por Medicamentos/etiologia
Feminino
Géis
Seres Humanos
Bombas de Infusão
Jejuno
Levodopa/administração & dosagem
Levodopa/uso terapêutico
Masculino
Meia-Idade
Dor/etiologia
Estudos Prospectivos
Qualidade de Vida
Federação Russa
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiparkinson Agents); 0 (Drug Combinations); 0 (Gels); 0 (carbidopa, levodopa drug combination); 46627O600J (Levodopa); MNX7R8C5VO (Carbidopa)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170810
[Lr] Data última revisão:
170810
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170405
[St] Status:MEDLINE
[do] DOI:10.17116/jnevro20171172122-31



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