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[PMID]:28470986
[Au] Autor:Wang L; Wang Y; Chai Y; Kang Y; Sun C; Zeng S
[Ad] Endereço:Institute of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China.
[Ti] Título:Nickel(II)-assisted enantiomeric differentiation and quantitation of tadalafil by direct electrospray ionization mass spectrometry.
[So] Source:J Mass Spectrom;52(7):411-416, 2017 Jul.
[Is] ISSN:1096-9888
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A facile method based on electrospray mass spectrometry was established and validated for the differentiation of enantiomeric tadalafil isomers without using chiral chromatographic separation. The enantiomers were coupled with a chiral selector to form diastereomeric complex ions. Nickel-tadalafil complexes, [Ni (tadalafil)(l-Trp)-H] , produced a characteristic fragment ion at m/z 524 by loss of 1-methyl-1,6-dihydropyrazine-2,5-dione via collision-induced dissociation. The relative abundance of this fragment ion to the precursor contributed to differentiate tadalafil enantiomers, and energy-resolved product-ion spectra were applied to determine the molar composition of tadalafil in the mixture (R,R and S,S) as well. In addition, the other two forms of stereomeric isomers of tadalafil (R,S and S,R) could be also distinguished and analyzed by this method. The method was validated in different types of mass spectrometers (AB quadrupole time-of-flight and Bruker ion trap) and also verified by a chiral high-performance liquid chromatography coupled with quadrupole time-of-flight. The chiral determination of tadalafil using MS method proved to be rapid (1-min run time for each sample) and to have the same accuracy and precision comparable to chiral liquid chromatography mass spectrometry methods. This method provides an alternative to commonly used chromatographic technique for chiral determination and is particularly useful in rapid screening in enantioselective synthesis and enantiomeric impurity detection in pharmaceutical industry. Copyright © 2017 John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Complexos de Coordenação/análise
Níquel/química
Inibidores da Fosfodiesterase 5/análise
Tadalafila/análise
[Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão/métodos
Complexos de Coordenação/química
Contaminação de Medicamentos
Conformação Molecular
Inibidores da Fosfodiesterase 5/química
Espectrometria de Massas por Ionização por Electrospray/métodos
Estereoisomerismo
Tadalafila/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Coordination Complexes); 0 (Phosphodiesterase 5 Inhibitors); 742SXX0ICT (Tadalafil); 7OV03QG267 (Nickel)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1002/jms.3939


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[PMID]:29202488
[Au] Autor:Ceci R; Duranti G; Sgrò P; Sabatini S; Di Luigi L
[Ad] Endereço:Università degli Studi di Roma "Foro Italico", Department of Movement, Human and Health Sciences, Unit of Biology, Genetics and Biochemistry, Rome, Italy.
[Ti] Título:Acute tadalafil administration increases plasma fatty acids without changes in the inflammatory response in healthy men.
[So] Source:Acta Biochim Pol;64(4):687-691, 2017.
[Is] ISSN:1734-154X
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Tadalafil, the phosphodiesterase type 5 inhibitor (PDE5I), has been shown to reduce visceral adipose tissue in rabbit and to improve lean mass content in non-obese men. In order to clarify this effect in humans, in the present study we determined the impact of an acute oral tadalafil administration on lipolysis by evaluating plasma free fatty acids (FFAs) and glycerol. FFAs are potential modulator of inflammation response that we evaluated through tumor necrosis factor alpha (TNFα), interleukin 6 (IL6), interleukin 8 (IL8) and interleukin 10 (IL10) plasma levels. Moreover, we determined whether the effects of tadalafil would be reflected in variation of plasma levels of cGMP and NO, two important molecules involved in PDE5Is signaling. METHODS: Twelve healthy subjects were supplemented with 20 mg of tadalafil or a placebo, in a double-blind, randomized, cross-over design. Blood samples were collected immediately before, and at 2, 6, and 24 hours post ingestion, and assayed for biochemical analysis. RESULTS: A condition effect was noted for FFAs and glycerol, with values higher for tadalafil when compared to the placebo group, at 2 and 6 hours post ingestion. No statistically significant effects were noted for glucose, cGMP, nitrate and nitrite. No inflammatory response was induced by tadalafil. CONCLUSION: Tadalafil, in human subjects, increases lipolysis as evidenced by a significant increase in circulating FFAs and glycerol, without affecting the plasma cGMP and NO levels; noticeably, the increase in FFAs did not develop an inflammatory response. Further well-controlled studies are warranted to assess the impact of tadalafil administration on weight/fat loss.
[Mh] Termos MeSH primário: Ácidos Graxos/sangue
Inflamação/sangue
Inibidores da Fosfodiesterase 5/administração & dosagem
Tadalafila/administração & dosagem
[Mh] Termos MeSH secundário: Adulto
Glicemia/metabolismo
GMP Cíclico/sangue
Método Duplo-Cego
Glicerol/sangue
Seres Humanos
Interleucina-6/sangue
Interleucina-8/sangue
Masculino
Óxido Nítrico/sangue
Fator de Necrose Tumoral alfa/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Blood Glucose); 0 (Fatty Acids); 0 (IL6 protein, human); 0 (IL8 protein, human); 0 (Interleukin-6); 0 (Interleukin-8); 0 (Phosphodiesterase 5 Inhibitors); 0 (Tumor Necrosis Factor-alpha); 31C4KY9ESH (Nitric Oxide); 742SXX0ICT (Tadalafil); H2D2X058MU (Cyclic GMP); PDC6A3C0OX (Glycerol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.18388/abp.2017_2205


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[PMID]:28450170
[Au] Autor:Choi JS; Kwon SH; Lee SE; Jang WS; Byeon JC; Jeong HM; Park JS
[Ad] Endereço:College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea.
[Ti] Título:Use of acidifier and solubilizer in tadalafil solid dispersion to enhance the in vitro dissolution and oral bioavailability in rats.
[So] Source:Int J Pharm;526(1-2):77-87, 2017 Jun 30.
[Is] ISSN:1873-3476
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The purpose of this study is to improve the solubility, in vitro dissolution, and oral bioavailability in rats of tadalafil (TDF) by using SD technique with a weak acid and a copolymer. TDF-SD was prepared via solvent evaporation, coupled with the incorporation of an acidifier and solubilizer. Tartaric acid enhanced the solubility of TDF over 5-fold in DW, and Soluplus enhanced the solubility of TDF over 8.7-fold and 19.2-fold compared to that of TDF (pure) in DW and pH 1.2 for 1h, respectively. The optimal formulation of TDF-SD3 was composed of TDF vs Tartaric acid vs Soluplus vs Aerosil=1:1:3:3. The in vitro dissolution rate of TDF-SD3 in DW, pH 1.2 and pH 6.8 buffer (51.5%, 53.3%, and 33.2%, respectively) was significantly higher than that of the commercial product (Cialis ) powder (16.5%, 15.2%, and 14.8%, respectively). TDF was completely transformed to an amorphous form as shown in SEM, DSC and PXRD data. The stability of TDF-SD3 included drug contents and in vitro dissolution for 1 month were similar to those of Cialis , and the amorphous form of TDF-SD3 was well maintained for 6 months. The TDF-SD3 formulation improved the relative bioavailability (BA) and peak plasma concentration (C ) compared to that of Cialis powder after oral administration in rats as 117.3% and 135.7%, respectively. From the results, we found that the acidifier increased the wettability of TDF, and the solubilizer improved solubility through hydrogen bonding with TDF, thereby increasing the solubility, dissolution and oral bioavailability of TDF in TDF-SD3.
[Mh] Termos MeSH primário: Disponibilidade Biológica
Tadalafila/química
Tadalafila/farmacocinética
[Mh] Termos MeSH secundário: Administração Oral
Animais
Células CACO-2
Química Farmacêutica
Composição de Medicamentos
Seres Humanos
Masculino
Polietilenoglicóis/química
Polivinil/química
Ratos
Ratos Sprague-Dawley
Solubilidade
Tartaratos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Polyvinyls); 0 (Tartrates); 0 (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer); 30IQX730WE (Polyethylene Glycols); 742SXX0ICT (Tadalafil); W4888I119H (tartaric acid)
[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:170429
[St] Status:MEDLINE


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Czeczko, Nicolau Gregori
Malafaia, Osvaldo
Texto completo SciELO Brasil
[PMID]:29236802
[Au] Autor:Wietzikoski EGG; Foiatto JC; Czeczko NG; Malafaia O; Koleski FC; Mierzwa TC; Gomes RPX
[Ad] Endereço:Fellow Master degree, Postgraduate Program in Surgery Principles, Medical Research Institute, Faculdade Evangélica do Paraná (FEPAR), Curitiba-PR, Brazil. Conception, design, intellectual and scientific content of the study; manuscript preparation.
[Ti] Título:Tadalafil protector effect during ischemia-reperfusion in rats.
[So] Source:Acta Cir Bras;32(11):973-983, 2017 Nov.
[Is] ISSN:1678-2674
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To evaluate histological parameters in rat renal tissue after tadalafil use during hot ischemia for 45 minutes and reperfusion for 24 hours. METHODS: Twenty rats were divided into 2 groups. In the experimental group 10 mg/kg of tadalafil was used per gavage before the procedure. All cases underwent left partial nephrectomy, followed by 45 minutes of warm ischemia. Left nephrectomy of the remaining kidney was performed after 24 hours from the initial procedure. The histological parameters analyzed were: detachment of tubular cells, accumulation of desquamated cells in the proximal tubule, loss of brush border, tubular cylinders, interstitial edema, leukocyte infiltration, capillary congestion, vacuolization, tubular dilatation, necrosis and collapse of the capillary tuft. RESULTS: Two rats from each group died and were excluded from the study. Tadalafil significantly reduced leukocyte infiltration (p = 0.036). The remaining histological parameters did not show statistical difference between the groups. CONCLUSION: The use of tadalafil during warm ischemia and reperfusion demonstrates statistically significant reduction of leukocyte infiltration in the renal interstitium.
[Mh] Termos MeSH primário: Rim/efeitos dos fármacos
Rim/patologia
Traumatismo por Reperfusão/prevenção & controle
Tadalafila/uso terapêutico
Vasodilatadores/uso terapêutico
[Mh] Termos MeSH secundário: Lesão Renal Aguda/tratamento farmacológico
Animais
Rim/irrigação sanguínea
Masculino
Distribuição Aleatória
Ratos
Ratos Wistar
Traumatismo por Reperfusão/tratamento farmacológico
Traumatismo por Reperfusão/patologia
Tadalafila/farmacologia
Fatores de Tempo
Vasodilatadores/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vasodilator Agents); 742SXX0ICT (Tadalafil)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171214
[St] Status:MEDLINE


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Texto completo SciELO Brasil
[PMID]:28977204
[Au] Autor:Oliveira GG; Oliveira SAH; Botelho PHH; Oliveira MAB; Bian K; Murad F
[Ad] Endereço:Universidade Católica de Brasília (UCB), Brasília, DF, Brazil.
[Ti] Título:Tadalafil: Protective Action against the Development of Multiple Organ Failure Syndrome.
[So] Source:Braz J Cardiovasc Surg;32(4):312-317, 2017 Jul-Aug.
[Is] ISSN:1678-9741
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Multiple organ failure syndrome (MOFS) is a pathology associated to unspecified and severe trauma, characterized by elevated morbidity and mortality. The complex inflammatory MOFS-related reactions generate important ischemia-reperfusion responses in the induction of this syndrome. Nitric oxide elevation, through the activation of cyclic guanosine monophosphate (cGMP), has the potential of counteracting the typical systemic vasoconstriction, and platelet-induced hypercoagulation. Tadalafil would possibly act protectively by reducing cGMP degradation with consequent diffuse vasodilatation, besides reduction of platelet-induced hypercoagulation, thus, preventing multiple organ failure syndrome development. METHODS: The experimental protocol was previously approved by an institution animal research committee. Experimental MOFS was induced through the stereotaxic micro-neurosurgical bilateral anterior hypothalamic lesions model. Groups of 10 Wistar rats were divided into: a) Non-operated control; b) Operated control group; c) 2 hours after tadalafil-treated operated group; d) 4 hours after tadalafil-treated operated group; e) 8 hours after post-treated operated group. The animals were sacrificed 24 hours after the neurosurgical procedure and submitted to histopathologic examination of five organs: brain, lungs, stomach, kidneys, and liver. RESULTS: The electrolytic hypothalamic lesions resulted in a full picture of MOFS with disseminated multiple-organs lesions, provoked primarily by diffusely spread micro-thrombi. The treatment with tadalafil 2 hours after the micro-neurosurgical lesions reduced the experimental MOFS lesions development, in a highly significant level (P<0.01) of 58.75%. The treatment with tadalafil, 4 hours after the micro-neurosurgically-induced MOFS lesions, also reduced in 49.71%, in a highly significant level (P<0.01). Finally, the treatment with tadalafil 8 hours after the neurosurgical procedure resulted in a statistically significant reduction of 30.50% (P<0.05) of the experimentally-induced MOFS gravity scores. CONCLUSION: The phosphodiesterase 5 inhibitor, tadalafil, in the doses and timing utilized, showed to protect against the experimentally-induced MOFS.
[Mh] Termos MeSH primário: Insuficiência de Múltiplos Órgãos/prevenção & controle
Inibidores da Fosfodiesterase 5/uso terapêutico
Substâncias Protetoras/uso terapêutico
Tadalafila/uso terapêutico
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Progressão da Doença
Hipotálamo Anterior/lesões
Masculino
Insuficiência de Múltiplos Órgãos/classificação
Insuficiência de Múltiplos Órgãos/etiologia
Inibidores da Fosfodiesterase 5/administração & dosagem
Período Pré-Operatório
Substâncias Protetoras/administração & dosagem
Ratos Wistar
Técnicas Estereotáxicas
Tadalafila/administração & dosagem
Trombose/induzido quimicamente
Trombose/reabilitação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphodiesterase 5 Inhibitors); 0 (Protective Agents); 742SXX0ICT (Tadalafil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE


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[PMID]:28972192
[Au] Autor:Victor RG; Sweeney HL; Finkel R; McDonald CM; Byrne B; Eagle M; Goemans N; Vandenborne K; Dubrovsky AL; Topaloglu H; Miceli MC; Furlong P; Landry J; Elashoff R; Cox D; Tadalafil DMD Study Group
[Ad] Endereço:From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle University (M.E.), Newcastle Upon Tyne, UK; University Hospitals
[Ti] Título:A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy.
[So] Source:Neurology;89(17):1811-1820, 2017 Oct 24.
[Is] ISSN:1526-632X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD). METHODS: Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg ·d , tadalafil 0.6 mg·kg ·d , or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome. RESULTS: Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil ( = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil ( = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state. CONCLUSIONS: Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age. CLINICALTRIALSGOV IDENTIFIER: NCT01865084. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.
[Mh] Termos MeSH primário: Distrofia Muscular de Duchenne/tratamento farmacológico
Tadalafila/uso terapêutico
Vasodilatadores/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Área Sob a Curva
Criança
Relação Dose-Resposta a Droga
Método Duplo-Cego
Seguimentos
Glucocorticoides/uso terapêutico
Frequência Cardíaca/fisiologia
Seres Humanos
Cooperação Internacional
Masculino
Distrofia Muscular de Duchenne/psicologia
Qualidade de Vida
Testes de Função Respiratória
Resultado do Tratamento
Função Ventricular Esquerda
Caminhada/fisiologia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE III; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Glucocorticoids); 0 (Vasodilator Agents); 742SXX0ICT (Tadalafil)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171105
[Lr] Data última revisão:
171105
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1212/WNL.0000000000004570


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[PMID]:28607126
[Au] Autor:Lambert JA; Carlisle MA; Lam A; Aggarwal S; Doran S; Ren C; Bradley WE; Dell'Italia L; Ambalavanan N; Ford DA; Patel RP; Jilling T; Matalon S
[Ad] Endereço:From the Biochemistry, Structural and Stem Cell Biology, Graduate Biomedical Sciences (J.A.L.), Division of Molecular and Translational Biomedicine, Department of Anesthesiology and Perioperative Medicine (J.A.L., M.A.C., A.L., S.A., S.D., S.M.), Division of Neonatology, Department of Pediatrics (C.
[Ti] Título:Mechanisms and Treatment of Halogen Inhalation-Induced Pulmonary and Systemic Injuries in Pregnant Mice.
[So] Source:Hypertension;70(2):390-400, 2017 Aug.
[Is] ISSN:1524-4563
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Inhalation of oxidant gases has been implicated in adverse outcomes in pregnancy, but animal models to address mechanisms and studies to identify potential pregnancy-specific therapies are lacking. Herein, we show that inhalation of bromine at 600 parts per million for 30 minutes by pregnant mice on the 15th day of embryonic development results in significantly lower survival after 96 hours than an identical level of exposure in nonpregnant mice. On the 19th embryonic day, bromine-exposed pregnant mice have increased systemic blood pressure, abnormal placental development, severe fetal growth restriction, systemic inflammation, increased levels of circulating antiangiogenic short fms-like tyrosine kinase-1, and evidence of pulmonary and cardiac injury. Treatment with tadalafil, an inhibitor of type 5 phosphodiesterase, by oral gavage 1 hour post-exposure and then once daily thereafter, attenuated systemic blood pressures, decreased inflammation, ameliorated pulmonary and cardiac injury, and improved maternal survival (from 36% to 80%) and fetal growth. These pathological changes resemble those seen in preeclampsia. Nonpregnant mice did not exhibit any of these pathological changes and were not affected by tadalafil. These findings suggest that pregnant women exposed to bromine may require particular attention and monitoring for signs of preeclampsia-like symptoms.
[Mh] Termos MeSH primário: Bromo
Hipertensão
Lesão Pulmonar
Pré-Eclâmpsia
Síndrome de Resposta Inflamatória Sistêmica
Tadalafila/farmacologia
[Mh] Termos MeSH secundário: Animais
Bromo/metabolismo
Bromo/toxicidade
Modelos Animais de Doenças
Feminino
Retardo do Crescimento Fetal/induzido quimicamente
Hipertensão/tratamento farmacológico
Hipertensão/metabolismo
Hipertensão/fisiopatologia
Exposição por Inalação/efeitos adversos
Lesão Pulmonar/induzido quimicamente
Lesão Pulmonar/tratamento farmacológico
Lesão Pulmonar/metabolismo
Lesão Pulmonar/fisiopatologia
Camundongos
Oxidantes/metabolismo
Oxidantes/toxicidade
Inibidores da Fosfodiesterase 5/farmacologia
Placenta/efeitos dos fármacos
Placenta/fisiopatologia
Pré-Eclâmpsia/tratamento farmacológico
Pré-Eclâmpsia/metabolismo
Pré-Eclâmpsia/fisiopatologia
Gravidez
Síndrome de Resposta Inflamatória Sistêmica/induzido quimicamente
Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oxidants); 0 (Phosphodiesterase 5 Inhibitors); 742SXX0ICT (Tadalafil); SBV4XY874G (Bromine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170830
[Lr] Data última revisão:
170830
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1161/HYPERTENSIONAHA.117.09466


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[PMID]:28606335
[Au] Autor:Coelho Neto J; Lisboa FLC
[Ad] Endereço:Seção Técnica de Física e Química Legal - Divisão de Laboratório, Instituto de Criminalística da Polícia Civil de Minas Gerais, Rua Juiz de Fora, 400, CEP 30180-060 Belo Horizonte, MG, Brazil; Departamento de Física e Química, Instituto de Ciências Exatas e Informática, Pontifícia Universidade Católica de Minas Gerais, Avenida Dom José Gaspar, 500, CEP 30535-901 Belo Horizonte, MG, Brazil. Electronic address: jcoelhon@pucminas.br.
[Ti] Título:ATR-FTIR characterization of generic brand-named and counterfeit sildenafil- and tadalafil-based tablets found on the Brazilian market.
[So] Source:Sci Justice;57(4):283-295, 2017 Jul.
[Is] ISSN:1355-0306
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Viagra and Cialis are among the most counterfeited medicines in many parts of the world, including Brazil. Despite the many studies that have been made regarding discrimination between genuine and counterfeit samples, most published works do not contemplate generic and similar versions of these medicines and also do not explore excipients/adjuvants contributions when characterizing genuine and suspected samples. In this study, we present our findings in exploring ATR-FTIR spectral profiles for characterizing both genuine and questioned samples of several generic and brand-name sildenafil- and tadalafil-based tablets available on the Brazilian market, including Viagra and Cialis. Multi-component spectral matching (deconvolution), objective visual comparison and correlation tests were used during analysis. Besides from allowing simple and quick identification of counterfeits, results obtained evidenced the strong spectral similarities between generic and brand-named tablets employing the same active ingredient and the indistinguishability between samples produced by the same manufacturer, generic or not. For all sildenafil-based and some tadalafil-based tablets tested, differentiation between samples from different manufacturers, attributed to slight variations in excipients/adjuvants proportions, was achieved, thus allowing the possibility of tracing an unknown/unidentified tablet back to a specific manufacturer.
[Mh] Termos MeSH primário: Medicamentos Falsificados
Medicamentos Genéricos
Citrato de Sildenafila/síntese química
Espectroscopia de Infravermelho com Transformada de Fourier
Tadalafila/síntese química
[Mh] Termos MeSH secundário: Brasil
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Counterfeit Drugs); 0 (Drugs, Generic); 742SXX0ICT (Tadalafil); BW9B0ZE037 (Sildenafil Citrate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE


  9 / 1154 MEDLINE  
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[PMID]:28502943
[Au] Autor:Numata K; Shimoda K; Shibata Y; Shioya A; Tokuda Y
[Ad] Endereço:Department of General Medicine, Mito Kyodo General Hospital, Japan.
[Ti] Título:The Development of Cerebral Venous Thrombosis after Tadalafil Ingestion in a Patient with Antiphospholipid Syndrome.
[So] Source:Intern Med;56(10):1235-1237, 2017.
[Is] ISSN:1349-7235
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:We report a case of cerebral venous thrombosis related to the ingestion of tadalafil. A 45-year-old man presented with posterior headache and was diagnosed with tension headache. Five days later, he was transported to our hospital via ambulance due to a tonic-clonic seizure. Head MRI showed cerebral venous thrombosis (CVT). He confessed to having recently taken a large doses of tadalafil. His anti-cardiolipin antibody and anti-caldiolipin-ß2-glycoprotein-I complex antibody levels were elevated. Our case suggests the possibility that tadalafil is related to both cardiovascular complications and CVT in patients with hypercoagulability. Patients with conditions associated with hypercoagulability, including antiphospholipid syndrome may be better advised to avoid the use of tadalafil.
[Mh] Termos MeSH primário: Síndrome Antifosfolipídica/complicações
Síndrome Antifosfolipídica/tratamento farmacológico
Encéfalo/diagnóstico por imagem
Trombose Intracraniana/diagnóstico
Trombose Intracraniana/etiologia
Tadalafila/efeitos adversos
Tadalafila/uso terapêutico
[Mh] Termos MeSH secundário: Encéfalo/fisiopatologia
Seres Humanos
Imagem por Ressonância Magnética
Masculino
Meia-Idade
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
742SXX0ICT (Tadalafil)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.2169/internalmedicine.56.7864


  10 / 1154 MEDLINE  
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[PMID]:28399643
[Au] Autor:Alp HH; Huyut Z; Yildirim S; Basbugan Y; Ediz L; Sekeroglu MR
[Ad] Endereço:1 Faculty of Medicine, Department of Biochemistry, Yuzuncu Yil University, Van 65080, Turkey.
[Ti] Título:The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.
[So] Source:Exp Biol Med (Maywood);242(10):1051-1061, 2017 May.
[Is] ISSN:1535-3699
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3',5'-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre- and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3',5'-cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis. Chemical compounds studied in this article Udenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634). Impact statement The results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance.
[Mh] Termos MeSH primário: Osso e Ossos/patologia
Osteoporose/tratamento farmacológico
Ovariectomia/efeitos adversos
Inibidores da Fosfodiesterase 5/administração & dosagem
Pirimidinas/administração & dosagem
Sulfonamidas/administração & dosagem
Tadalafila/administração & dosagem
Dicloridrato de Vardenafila/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Biomarcadores/análise
Densidade Óssea
Cromatografia Líquida de Alta Pressão
Modelos Animais de Doenças
Ensaio de Imunoadsorção Enzimática
Ratos Wistar
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Phosphodiesterase 5 Inhibitors); 0 (Pyrimidines); 0 (Sulfonamides); 5O8R96XMH7 (Vardenafil Dihydrochloride); 742SXX0ICT (Tadalafil); L5IB4XLY36 (udenafil)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170413
[St] Status:MEDLINE
[do] DOI:10.1177/1535370217703352



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