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2.
J Infect Chemother ; 29(11): 1075-1080, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37451619

RESUMO

Klebsiella pneumoniae (Kpn) is one of the most common gram-negative bacilli causing lung, urinary tract, and biliary tract infections. However, as a distinct entity from classic Kpn, hypervirulent Kpn causing liver abscess, endophthalmitis, and lung abscess with poor prognoses has been reported mainly in East and Southeast Asia since the mid-1980s. Although the definition of hypervirulent Kpn is unclear, the hypermucoviscosity of Kpn is considered an important feature of hypervirulence. We present a case of emphysematous pyelonephritis accompanied by septic shock and acute kidney injury caused by hypermucoviscous Kpn infection that was successfully treated by intensive treatment. A 70-year-old woman with type 2 diabetes mellitus was diagnosed with emphysematous pyelonephritis, and string test-positive Kpn was detected in blood and urine cultures and percutaneous catheter drainage fluid from the renal pelvis. The patient was treated with intensive therapies including antibiotics, ventilator management, and continuous hemodiafiltration (CHDF) using AN69ST, which can absorb cytokines. During the course of treatment, the infection was complicated by pyogenic spondylitis, which was cured by antimicrobial therapy, and the patient was transferred to another hospital for rehabilitation on day 119 after admission. Hypermucoviscous Kpn infection often has a severe course, and it is important to initiate multidisciplinary treatment at an early stage, including rifampicin, which is expected to inhibit the viscosity of hypermucoviscous Kpn. In the current case, immediate CHDF using AN69ST was also considered a life-saving treatment because it improved both volume overload and neutrophil-activated hypercytokinemia.


Assuntos
Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Hemodiafiltração , Infecções por Klebsiella , Abscesso Hepático , Pielonefrite , Feminino , Humanos , Idoso , Klebsiella pneumoniae , Diabetes Mellitus Tipo 2/complicações , Pielonefrite/complicações , Complicações do Diabetes/complicações , Infecções por Klebsiella/complicações , Infecções por Klebsiella/tratamento farmacológico
3.
Diagnostics (Basel) ; 12(2)2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-35204430

RESUMO

Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.

4.
Mod Rheumatol Case Rep ; 4(2): 248-252, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33086997

RESUMO

A 52-year-old woman was diagnosed as having anti-centromere antibody (ACA)-positive primary Sjögren syndrome (pSS). Eight years later, she visited our hospital because she had developed dyspnoea. She was diagnosed as having pulmonary arterial hypertension (PAH) with pulmonary veno-occlusive disease on the basis of the results of right heart catheterisation, a severe decrease in diffusing capacity of the lung for carbon monoxide (DLCO, 17%) and desaturation (69%) after a 6-minute walk test. She was also diagnosed as having limited cutaneous systemic sclerosis (lcSSc) because she had developed finger sclerosis. The six-minute walk distance had improved by 54 m 3 months after commencing treatment with tadalafil. Clinicians should be alert to the possibility of patients with ACA-positive SS developing lcSSc and PAH during their clinical course.


Assuntos
Anticorpos Antinucleares/imunologia , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Esclerodermia Limitada/diagnóstico , Esclerodermia Limitada/etiologia , Síndrome de Sjogren/complicações , Síndrome de Sjogren/imunologia , Autoanticorpos/imunologia , Autoimunidade , Biomarcadores , Suscetibilidade a Doenças , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/tratamento farmacológico
5.
Bioorg Med Chem ; 28(5): 115307, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32007387

RESUMO

Adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a key role in maintaining cellular metabolism. AMP or adenosine diphosphate (ADP) levels rise during metabolic stress, such as during nutrient starvation, hypoxia and muscle contraction, and bind to AMPK to induce activity. Recently, activation of AMPK has been considered an attractive therapeutic strategy in the field of human oncology. Structural optimization of lead compound 2, a new type of AMPK activator with potent AMPK activation activity and attractive selective growth inhibition against human cancer cells, improved aqueous solubility, metabolic stability and animal pharmacokinetics (PK) and culminated in the identification of (5-{1-[(6-methoxypyridin-3-yl)methyl]piperidin-4-yl}-1H-benzimidazol-2-yl)(4-{[4-(trifluoromethyl)phenyl]methyl}piperazin-1-yl)methanone ditosylate, ASP4132 (28). Studies on ASP4132 had advanced to clinical trials for the treatment of cancer.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Desenvolvimento de Medicamentos , Inibidores de Proteínas Quinases/farmacologia , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Camundongos , Camundongos Nus , Estrutura Molecular , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/química , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
6.
Bioorg Med Chem ; 25(21): 6024-6038, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28988626

RESUMO

Vascular adhesion protein-1 (VAP-1) is a promising therapeutic target for the treatment of diabetic nephropathy. Here, we conducted structural optimization of the glycine amide derivative 1, which we previously reported as a novel VAP-1 inhibitor, to improve stability in dog and monkey plasma, and aqueous solubility. By chemical modification of the right part in the glycine amide derivative, we identified the carbamimidoylcarbamate derivative 20c, which showed stability in dog and monkey plasma while maintaining VAP-1 inhibitory activity. We also found that conversion of the pyrimidine ring in 20c into saturated rings was effective for improving aqueous solubility. This led to the identification of 28a and 35 as moderate VAP-1 inhibitors with excellent aqueous solubility. Further optimization led to the identification of 2-fluoro-3-{3-[(6-methylpyridin-3-yl)oxy]azetidin-1-yl}benzyl carbamimidoylcarbamate (40b), which showed similar human VAP-1 inhibitory activity to 1 with improved aqueous solubility. 40b showed more potent ex vivo efficacy than 1, with rat plasma VAP-1 inhibitory activity of 92% at 1h after oral administration at 0.3mg/kg. In our pharmacokinetic study, 40b showed good oral bioavailability in rats, dogs, and monkeys, which may be due to its improved stability in dog and monkey plasma.


Assuntos
Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Carbamatos/farmacologia , Moléculas de Adesão Celular/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Administração Oral , Amina Oxidase (contendo Cobre)/sangue , Amina Oxidase (contendo Cobre)/metabolismo , Animais , Carbamatos/administração & dosagem , Carbamatos/química , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/metabolismo , Cães , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Injeções Intravenosas , Macaca fascicularis , Masculino , Estrutura Molecular , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade
7.
Bioorg Med Chem ; 22(24): 6899-907, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25456079

RESUMO

N-type calcium channels represent a promising target for the treatment of neuropathic pain. The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration. We identified tetrahydroisoquinoline derivative 1a as a novel potent N-type calcium channel blocker. However, this compound also exhibited potent inhibitory activity against hERG channels. Structural optimizations led to identification of (1S)-(1-cyclohexyl-3,4-dihydroisoquinolin-2(1H)-yl)-2-{[(1-hydroxycyclohexyl)methyl]amino}ethanone ((S)-1h), which exhibited high selectivity for hERG channels while retaining potency for N-type calcium channel inhibition. (S)-1h went on to demonstrate in vivo efficacy as an orally available N-type calcium channel blocker in a rat spinal nerve ligation model of neuropathic pain.


Assuntos
Bloqueadores dos Canais de Cálcio/química , Canais de Cálcio Tipo N/metabolismo , Canais de Potássio Éter-A-Go-Go/metabolismo , Tetra-Hidroisoquinolinas/química , Animais , Bloqueadores dos Canais de Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canais de Cálcio Tipo N/química , Linhagem Celular Tumoral , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Avaliação Pré-Clínica de Medicamentos , Canais de Potássio Éter-A-Go-Go/química , Humanos , Masculino , Neuralgia/tratamento farmacológico , Ligação Proteica , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Tetra-Hidroisoquinolinas/metabolismo , Tetra-Hidroisoquinolinas/uso terapêutico
8.
Bioorg Med Chem ; 22(21): 6026-38, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25281269

RESUMO

A series of 9-disubstituted N-(9H-fluorene-2-carbonyl)guanidine derivatives have been discovered as potent and orally active dual 5-HT(2B) and 5-HT(7) receptor antagonists. Upon screening several compounds, N-(diaminomethylene)-4',5'-dihydro-3'H-spiro[fluorene-9,2'-furan]-2-carboxamide (17) exhibited potent affinity for both 5-HT(2B) (Ki = 5.1 nM) and 5-HT(7) (K(i) = 1.7 nM) receptors with high selectivity over 5-HT(2A), 5-HT(2C), α(1), D(2) and M(1) receptors. Optical resolution of the intermediate carboxylic acid 16 via the formation of diastereomeric salts using chiral alkaloids gave the optically pure compounds (R)-17 and (S)-17. Both enantiomers suppressed 5-HT-induced dural protein extravasation in guinea pigs in a dose-dependent manner and the amount of leaked protein was suppressed to near normal levels when orally administrated at 10 mg/kg. (R)-17 and (S)-17 were therefore selected as candidates for human clinical trials.


Assuntos
Receptor 5-HT2B de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/química , Antagonistas da Serotonina/farmacologia , Animais , Células CHO , Cricetulus , Cobaias , Células HEK293 , Humanos , Simulação de Acoplamento Molecular , Antagonistas do Receptor 5-HT2 de Serotonina/síntese química , Antagonistas do Receptor 5-HT2 de Serotonina/química , Antagonistas do Receptor 5-HT2 de Serotonina/farmacologia , Antagonistas da Serotonina/síntese química
9.
Bioorg Med Chem ; 22(15): 4323-37, 2014 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-24916029

RESUMO

We previously reported that the novel dual 5-HT2B and 5-HT7 receptor antagonist N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (4) exerted a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs. To develop a synthetic strategy, we performed docking studies of lead compound 4 bound to 5-HT2B and 5-HT7 receptors, and observed that the carbonyl guanidine group forms a tight interaction network with an active center Asp (D135:5-HT2B, D162:5-HT7), Tyr (Y370:5-HT2B, Y374:5-HT7) and aromatic residue (W131:5-HT2B, F158:5-HT7). Based on molecular modeling results, we optimized the substituents at the 5- to 8-position and 9-position of the fluorene ring and identified N-(diaminomethylene)-9-hydroxy-9-methyl-9H-fluorene-2-carboxamide (24a) exhibits potent affinity for 5-HT2B (Ki=4.3 nM) and 5-HT7 receptor (Ki=4.3 nM) with high selectivity over 5-HT2A, 5-HT2C, α1, D2 and M1 receptors. Compound 24a reversed the hypothermic effect of 5-carboxamidotryptamine (5-CT) in mice and also showed a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs when orally administered at 30 mg/kg. Compound 24a is therefore a promising candidate for a novel class of anti-migraine agent without any adverse effects.


Assuntos
Guanidina/análogos & derivados , Receptor 5-HT2B de Serotonina/química , Receptores de Serotonina/química , Antagonistas da Serotonina/síntese química , Administração Oral , Animais , Sítios de Ligação , Temperatura Corporal/efeitos dos fármacos , Células CHO , Cricetinae , Cricetulus , Guanidina/síntese química , Guanidina/farmacocinética , Cobaias , Células HEK293 , Humanos , Hipotermia Induzida , Masculino , Camundongos , Simulação de Acoplamento Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Receptor 5-HT2B de Serotonina/genética , Receptor 5-HT2B de Serotonina/metabolismo , Receptores de Serotonina/genética , Receptores de Serotonina/metabolismo , Serotonina/análogos & derivados , Serotonina/farmacologia , Antagonistas da Serotonina/química , Antagonistas da Serotonina/farmacocinética , Relação Estrutura-Atividade
10.
Bioorg Med Chem ; 21(24): 7841-52, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24189186

RESUMO

To identify potent dual 5-HT2B and 5-HT7 receptor antagonists, we synthesized a series of novel carbonyl guanidine derivatives and examined their structure-activity relationships. Among these compounds, N-(9-hydroxy-9H-fluorene-2-carbonyl)guanidine (10) had a good in vitro profile, that is, potent affinity for human 5-HT2B and 5-HT7 receptor subtypes (Ki=1.8 nM and Ki=17.6 nM, respectively) and high selectivity over 5-HT2A, 5-HT2C, α1, D2 and M1 receptors. Compound 10 also showed a suppressing effect on 5-HT-induced dural protein extravasation in guinea pigs when orally administered.


Assuntos
Guanidina/análogos & derivados , Guanidina/farmacologia , Receptor 5-HT2B de Serotonina/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/química , Antagonistas da Serotonina/farmacologia , Relação Dose-Resposta a Droga , Guanidina/química , Humanos , Estrutura Molecular , Antagonistas da Serotonina/síntese química , Relação Estrutura-Atividade
11.
J Colloid Interface Sci ; 297(2): 672-7, 2006 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-16313919

RESUMO

Calcination of a cerium-S-phenylene-O-holmium-O-phenylene-S hybrid copolymer under a vacuum gave cerium oxide-carbon cluster-holmium oxide composite material. The material calcined at 600 degrees C loaded with Pt particles could decompose water to H2 and O2 with a H2/O2 ratio of 2 under visible light irradiation. ESR spectral examinations of the calcined materials revealed the possibility of a two-step electron transfer in the process of CeO2 --> carbon cluster --> Ho2O3 --> Pt with an oxidation site at CeO2 particles and a reduction site at Pt particles.

12.
Int Heart J ; 46(5): 933-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16272786

RESUMO

A 62-year-old woman was struck by lightning while on a mountain and fortunately did not suffer burns or unconsciousness. She stayed at a mountain lodge overnight and was taken to our hospital by helicopter the next day. Upon admission, electrocardiography showed ST segment elevation indicating acute lateral myocardial infarction, and echocardiography showed takotsubo-shaped hypokinesis of the left ventricle indicating an apical aneurysm. Her serum escaped enzyme levels were increased, as is typical in cases of myocardial infarction, however, she did not complain of cardiac symptoms. Coronary arteriography performed 4 days after admission showed a normal coronary artery while left ventriculography showed apical akinesia. An echocardiogram obtained 2 days later showed resolution of the LV wall motion abnormality. This is the first reported case of takotsubo cardiomyopathy caused by lightning. Takotsubo-shaped hypokinesis is not described as a complication of lightning-induced cardiac injury and its pathogenesis remains controversial.


Assuntos
Cardiomiopatias/etiologia , Traumatismos Cardíacos/etiologia , Hipocinesia/etiologia , Lesões Provocadas por Raio/complicações , Aspirina/administração & dosagem , Cardiomiopatias/tratamento farmacológico , Quimioterapia Combinada , Feminino , Ventrículos do Coração/patologia , Humanos , Dinitrato de Isossorbida/administração & dosagem , Dinitrato de Isossorbida/análogos & derivados , Pessoa de Meia-Idade , Montanhismo
13.
Chem Pharm Bull (Tokyo) ; 53(8): 1043-7, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16079546

RESUMO

In the setting of heart failure and myocardial ischemia-reperfusion, the sodium-calcium exchanger (NCX) can lead to calcium overload, which is responsible for contractile dysfunction and arrhythmia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of benzyloxyphenyl derivatives based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward modes of NCX. We have discovered a novel potent and selective reverse NCX inhibitor (12) with an IC50 value of 0.085 microM against reverse NCX.


Assuntos
Acetamidas/química , Piridinas/química , Trocador de Sódio e Cálcio/antagonistas & inibidores , Espectroscopia de Ressonância Magnética , Espectrometria de Massas de Bombardeamento Rápido de Átomos
14.
Bioorg Med Chem ; 13(12): 4022-36, 2005 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-15911315

RESUMO

Ca(2+) overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium-hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca(2+) overload, because NCX inhibitors can directly inhibit the influx of Ca(2+) into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reperfusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23 h) with an IC(50) value of 0.12 microM against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23 h are discussed.


Assuntos
Bloqueadores dos Canais de Cálcio/síntese química , Niacinamida/análogos & derivados , Trocador de Sódio e Cálcio/antagonistas & inibidores , Administração Oral , Animais , Disponibilidade Biológica , Cálcio/metabolismo , Bloqueadores dos Canais de Cálcio/farmacologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Modelos Animais de Doenças , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Concentração Inibidora 50 , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Niacinamida/síntese química , Niacinamida/farmacologia , Farmacocinética , Ratos , Ratos Endogâmicos , Relação Estrutura-Atividade
15.
Chem Pharm Bull (Tokyo) ; 53(4): 448-50, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15802851

RESUMO

A practical and cost-effective procedure has been developed for the synthesis of 7-methyl-2-naphthalenecarbonitrile, the precursor of the anticoagulant agents YM-60828 or YM-96765. This new route generates the key intermediate in only two steps from readily available 3-cyanopropionaldehyde dimethyl acetal and m-tolualdehyde, without requiring chromatographic purification. The synthesis involves condensation of the cyano derivative with the aldehyde and subsequent cyclodehydration.


Assuntos
Anticoagulantes/síntese química , Naftalenos/síntese química , Nitrilas/síntese química , Benzaldeídos , Cromatografia em Camada Fina , Compostos Heterocíclicos/síntese química , Espectroscopia de Ressonância Magnética , Piperidinas/síntese química , Espectrofotometria Ultravioleta
16.
Bioorg Med Chem ; 13(3): 725-34, 2005 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-15653340

RESUMO

In the context of heart failure and myocardial ischemia reperfusion, the activity of the sodium-calcium exchanger can lead to calcium overload, which in turn can lead to contractile dysfunction and arrhythmia. Therefore, NCX is an attractive target for treatment of heart failure and myocardial ischemia reperfusion. We have designed and synthesized a series of benzyloxyphenyl derivatives as potential NCX inhibitors, based on compound 4. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward modes of NCX, and two novel potent NCX inhibitors (7i, 10a) were discovered. Compound 7i was evaluated for its efficacy on ouabain-induced tonotropy and arrhythmia in a heart-failure model.


Assuntos
Compostos de Benzil/química , Compostos de Benzil/síntese química , Baixo Débito Cardíaco/tratamento farmacológico , Isquemia Miocárdica/tratamento farmacológico , Trocador de Sódio e Cálcio/química , Trocador de Sódio e Cálcio/farmacologia , Compostos de Benzil/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Trocador de Sódio e Cálcio/síntese química , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Relação Estrutura-Atividade
17.
Bioorg Med Chem ; 12(19): 5039-56, 2004 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-15351388

RESUMO

The sodium-calcium exchanger (NCX) is known as the transporter that controls the concentration of Ca(2+) in cardiac myocytes. In the setting of heart failure and myocardial ischemia-reperfusion, NCX underlies an arrhythmogenic transient inward current responsible for delayed after--depolarizations and nonreentrant initiation of ventricular tachycardia. NCX is an attractive target for treatment in heart failure and myocardial ischemia-reperfusion. We have designed and synthesized a series of phenoxypyridine derivatives, based on compound 3. These derivatives have been evaluated for their inhibitory activity against both the reverse and forward mode of NCX in CCL39 cells. We have discovered several novel potent NCX inhibitors (39q, 48k), which have a high selectivity for reverse NCX inhibitory activity.


Assuntos
Piridinas/síntese química , Piridinas/farmacologia , Trocador de Sódio e Cálcio/antagonistas & inibidores , Animais , Cálcio/metabolismo , Linhagem Celular , Cricetinae , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Concentração Inibidora 50 , Necrose/induzido quimicamente , Relação Estrutura-Atividade
18.
Intern Med ; 42(3): 268-72, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12705793

RESUMO

A young man with repetitive deep venous thrombosis of the legs and the inferior vena cava, and his family were eventually diagnosed by means of molecular genetic analysis as having both hereditary protein C and protein S deficiency. There have been a few reports of families with combined protein C and protein S deficiency and only one report of such a family characterized at the DNA level. This was the first reported family in Japan with combined deficiency of protein C and protein S accompanied by segregation of gene lesions.


Assuntos
Deficiência de Proteína C/complicações , Deficiência de Proteína C/genética , Deficiência de Proteína S/complicações , Deficiência de Proteína S/genética , Tromboembolia/complicações , Tromboembolia/genética , Trombose Venosa/complicações , Trombose Venosa/genética , Adulto , Segregação de Cromossomos , Análise Mutacional de DNA , Genótipo , Humanos , Masculino , Mutação Puntual , Recidiva
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