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1.
J Chem Crystallogr ; 43(5): 235-239, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23750099

RESUMO

The crystal structure of 8-((dimethylamino)methyl)-1-(3-(dimethylamino)propyl)-1,7,8,9-tetrahydrochromeno[5,6-d]imidazol-2-amine (1), an inhibitor of the hepatitis C virus internal ribosome entry site, is described and compared to the structure of the compound in complex with the viral RNA target. Compound 1 crystallized by pentane vapor diffusion into dichloroethane solution. It crystallized in the monoclinic system, P21/c space group with unit cell parameters a = 15.7950(5) Å, b = 14.0128(4) Å, c = 8.8147(3) Å, ß = 94.357(2)° and a cell volume of 1945.34(11) A-3. Packing interactions in the small molecule crystal lattice correspond to key interactions of the compound with the viral RNA target.

2.
Org Lett ; 15(11): 2598-600, 2013 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-23659323

RESUMO

A new route to the ergoline skeleton has been developed that does not require prior functionalization of the indole 4-position. The indole nucleus is introduced late in the synthesis to allow for eventual efficient introduction of substituents in this region. Key steps include Negishi coupling of a three-carbon chain to a bromonicotinate ester, Fischer indole synthesis to facilitate incorporation of substituents via phenylhydrazines, and Pd-catalyzed cyclization to form the ergoline C ring.


Assuntos
Ergolinas/química , Ergolinas/síntese química , Indóis/química , Niacina/química , Paládio/química , Fenil-Hidrazinas/química , Catálise , Ciclização , Estrutura Molecular
3.
Proc Natl Acad Sci U S A ; 109(14): 5223-8, 2012 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-22431596

RESUMO

The internal ribosome entry site (IRES) in the hepatitis C virus (HCV) RNA genome is essential for the initiation of viral protein synthesis. IRES domains adopt well-defined folds that are potential targets for antiviral translation inhibitors. We have determined the three-dimensional structure of the IRES subdomain IIa in complex with a benzimidazole translation inhibitor at 2.2 Å resolution. Comparison to the structure of the unbound RNA in conjunction with studies of inhibitor binding to the target in solution demonstrate that the RNA undergoes a dramatic ligand-induced conformational adaptation to form a deep pocket that resembles the substrate binding sites in riboswitches. The presence of a well-defined ligand-binding pocket within the highly conserved IRES subdomain IIa holds promise for the development of unique anti-HCV drugs with a high barrier to resistance.


Assuntos
Hepacivirus/genética , RNA Viral/química , Riboswitch , Benzimidazóis/farmacologia , Transferência Ressonante de Energia de Fluorescência , Ligantes , Modelos Moleculares , Conformação de Ácido Nucleico , Biossíntese de Proteínas/efeitos dos fármacos
4.
Molecules ; 16(1): 281-90, 2010 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-21193848

RESUMO

A class of dihydropyranobenzimidazole inhibitors was recently discovered that acts against the hepatitis C virus (HCV) in a new way, binding to the IRES-IIa subdomain of the highly conserved 5' untranslated region of the viral RNA and thus preventing the ribosome from initiating translation. However, the reported synthesis of these compounds is lengthy and low-yielding, the intermediates are troublesome to purify, and the route is poorly structured for the creation of libraries. We report a streamlined route to this class of inhibitors in which yields are far higher and most intermediates are crystalline. In addition, a key variable side chain is introduced late in the synthesis, allowing analogs to be easily synthesized for optimization of antiviral activity.


Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , Hepacivirus/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Regiões 5' não Traduzidas , Cromatografia Líquida de Alta Pressão , Hepacivirus/fisiologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Relação Estrutura-Atividade
5.
Scand J Public Health ; 29(2): 140-50, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11484867

RESUMO

AIMS: Lithuanian middle-aged men have a fourfold higher risk for coronary heart disease (CHD) mortality compared with Swedish men. In Sweden, CHD mortality is twice as high in blue- compared with white-collar workers. Whether the same risk factors that characterized Lithuanian men, compared with Swedish men, could be found in low socioeconomic groups within the cities was investigated. METHODS: The LiVicordia study compared both traditional and new possible risk factors for CHD among 150 50-year-old men in Linköping, Sweden and Vilnius, Lithuania. A comparison was made of the prevalence of these risk factors in high and low socioeconomic groups within the cities and, after controlling for the city, variations across socioeconomic groups in the total sample. RESULTS: Small differences were found in traditional risk factors between cities. However, Vilnius men were shorter, had lower serum levels of antioxidant vitamins, more psychosocial strain, and lower cortisol response to a standardized laboratory stress test. These characteristics were also found among men in low social classes in both cities. In linear regression models, short stature, low serum beta-carotene, low social integration, coping and self-esteem, high vital exhaustion, high baseline and low cortisol response to stress were related to low social class. CONCLUSIONS: The same set of risk factors, mainly relating to oxidative and psychosocial stress, that characterized Vilnius men was also found in men in low social classes within the cities. The results suggest that a common set of risk factors may help to explain health differences both between and within countries.


Assuntos
Doença das Coronárias/epidemiologia , Antioxidantes , Doença das Coronárias/etiologia , Doença das Coronárias/psicologia , Emprego/psicologia , Humanos , Hidrocortisona , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/fisiologia , Fatores de Risco , Classe Social , Fatores Socioeconômicos , Estresse Psicológico/complicações , Estresse Psicológico/fisiopatologia , Suécia/epidemiologia , Saúde da População Urbana , beta Caroteno/deficiência
6.
Atherosclerosis ; 151(2): 501-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10924727

RESUMO

Coronary heart disease mortality is four times higher in Lithuanian compared to Swedish middle-aged men. Using the same equipment (Acuson XP10 with 5 MHz linear transducer) and staff, we compared the amount of atherosclerosis in carotid and femoral arteries in 100 randomly sampled 50-year-old men in each of the cities Vilnius, Lithuania and Linköping, Sweden. Atherosclerotic plaques were more abundant in Vilnius men compared to Linköping men (53 versus 28% in the common carotid artery, 73 versus 37% in the common femoral artery, P < 0.001 for both). Plaques were thicker and more extended in arteries of Vilnius men, and an ultrasound atherosclerosis score was higher in both carotid and femoral arteries (P < 0.001 for all). More Vilnius men had a maximal intima-media thickness of the common femoral artery above 1 mm (P<0.005). Stiffness in the common carotid artery was higher in Vilnius men (P<0.001). In a linear regression model of the pooled material, after adjustment for city was made, smoking, systolic blood pressure, low density lipoprotein cholesterol and beta-carotene (inversely) significantly contributed to a high total ultrasound score (r2 = 0.32). These findings show that the higher coronary mortality noted in Lithuanian men goes together with a higher prevalence of early peripheral atherosclerosis.


Assuntos
Arteriosclerose/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Artéria Femoral/diagnóstico por imagem , Arteriosclerose/etiologia , Arteriosclerose/fisiopatologia , Artérias Carótidas/diagnóstico por imagem , Artérias Carótidas/fisiopatologia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Estudos Transversais , Elasticidade , Artéria Femoral/fisiopatologia , Humanos , Lituânia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suécia , Túnica Íntima/diagnóstico por imagem , Túnica Média/diagnóstico por imagem , Ultrassonografia
7.
Scand J Clin Lab Invest ; 59(3): 227-32, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10400167

RESUMO

The LiVicordia study was set up to investigate possible causes for coronary heart disease mortality in middle-aged Lithuanian men being four times higher than in Swedish men. In a previous part of this study we found lower total and low density lipoprotein (LDL) cholesterol in the Lithuanian men in spite of them having a higher fat intake than in the Swedish men. Their LDL was also more susceptible to oxidation in vitro than was that of the Swedish men. Fat quality can influence LDL oxidation. In order to obtain data on long-term fat quality intake we measured the fatty acid composition of abdominal wall adipose tissue by gas chromatography in men aged 50 years from Vilnius, Lithuania (n=50) and Linköping, Sweden (n=50). Men from Vilnius had a significantly higher percentage of adipose tissue long chain polyunsaturated fatty acids (PUFA) (20:4n6, 20:5n3, 22:5n5, 22:6n3) and lower percentage of saturated fatty acids, especially myristic acid (14:0), 3.4+/-0.7 versus 4.6+/-0.8, p<0.0001. The percentage content of adipose tissue linoleic acid (18:2n6) was 11.5+/-2.1 versus 11.0+/-1.4 (n.s.) and of linolenic acid (18:3n3) 0.7+/-0.3 versus 0.6+/-0.2 (n.s.) in men from Vilnius and Linköping, respectively. It is concluded that the adipose tissue content of essential fatty acids is similar in men from Vilnius and men from Linköping and therefore the intake is also likely to be similar. The higher contents of long chain highly unsaturated fatty acids in men from Vilnius may be of importance in the oxidation process of LDL.


Assuntos
Tecido Adiposo/química , Doença das Coronárias/epidemiologia , Doença das Coronárias/metabolismo , Ácidos Graxos Insaturados/análise , Ácidos Graxos/análise , Índice de Massa Corporal , Dieta Aterogênica , Gorduras na Dieta/análise , Humanos , Peroxidação de Lipídeos/fisiologia , Lipoproteínas LDL/metabolismo , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Ácido Mirístico/análise , Fatores de Risco , Suécia/epidemiologia , Ácido alfa-Linolênico/análise
8.
Psychosom Med ; 60(3): 277-82, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9625214

RESUMO

OBJECTIVE: Coronary heart disease (CHD) mortality is four times higher in 50-year-old Lithuanian men than in 50-year-old Swedish men. The difference cannot be explained by standard risk factors. The objective of this study was to examine differences in psychosocial risk factors for CHD in the two countries. METHODS: The LiVicordia study is a cross-sectional survey comparing 150 randomly selected 50-year-old men in each of the two cities: Vilnius, Lithuania, and Linköping, Sweden. As part of the study, a broad range of psychosocial characteristics, known to predict CHD, were investigated. RESULTS: In the men from Vilnius compared with those from Linköping, we found a cluster of psychosocial risk factors for CHD; higher job strain (p <.01), lower social support at work, lower emotional support, and lower social integration (p values <.001). Vilnius men also showed lower coping, self-esteem, and sense of coherence (p values < .001), higher vital exhaustion, and depression (p values < .001). Quality of life and perceived health were lower and expectations of ill health within 5 to 10 years were higher in Vilnius men (p values < .001). Correlations between measurements on traditional and psychosocial risk factors were few and weak. CONCLUSIONS: The Vilnius men, representing the population with a four-fold higher CHD mortality, had unfavorable characteristics on a cluster of psychosocial risk factors for CHD in comparison with the Linköping men. We suggest that this finding may provide a basis for possible new explanations of the differences in CHD mortality between Lithuania and Sweden.


Assuntos
Doença das Coronárias/psicologia , Comparação Transcultural , Estresse Psicológico/complicações , Doença das Coronárias/mortalidade , Estudos Transversais , Humanos , Satisfação no Emprego , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Risco , Apoio Social , Análise de Sobrevida , Suécia/epidemiologia
9.
Int J Behav Med ; 5(1): 17-30, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-16250713

RESUMO

Cardiovascular mortality rates of middle-aged men are 4 times higher in Lithuania than in Sweden The difference is not explained by standard risk factors, but our previous findings of pronounced psychosocial stress in Lithuanian men offer a possible explanation. We investigated cortisol and cardiovascular reactivity to a standardized laboratory stress test in population-based random samples of 50-year-old men from Vilnius, Lithuania and Linköping, Sweden. Repeated measures analysis of variance showed that cortisol responses differed between cities (p's < .0001). Mean change of serum cortisol from baseline to 30 min was 18.1 and 88.4 nmol/1 for Vilnius and Linkoping men, respectively (p < .001). In a multivariate analysis, a low peak cortisol response was significantly related to high baseline cortisol, current smoking, and vital exhaustion. The findings suggest a physiological mechanism of chronic psychosocial stress, which may contribute to increased risk for cardiovascular death.

10.
BMJ ; 314(7081): 629-33, 1997 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-9066473

RESUMO

OBJECTIVE: To investigate possible risk factors and mechanisms behind the four times higher and diverging mortality from coronary heart disease in Lithuanian compared with Swedish middle aged men. DESIGN: Concomitant cross sectional comparison of randomly selected 50 year old men without serious acute or chronic disease. Methods and equipment were identical or highly standardised between the centres. SETTING: Linköping (Sweden) and Vilnius (Lithuania). SUBJECTS: 101 and 109 men aged 50 in Linköping and Vilnius respectively. MAIN OUTCOME MEASURES: Anthropometric data, blood pressure, smoking, plasma lipid and lipoprotein concentrations, susceptibility of low density lipoprotein to oxidation, and plasma concentrations of fat soluble antioxidant vitamins. RESULTS: Systolic blood pressure was higher (141 v 133 mm Hg, P < 0.01), smoking habits were similar, and plasma total cholesterol (5.10 v 5.49 mmol/l, P < 0.01) and low density lipoprotein cholesterol (3.30 v 3.68 mmol/l, P < 0.01) lower in men from Vilnius compared with those from Linköping. Triglyceride, high density lipoprotein cholesterol, and Lp(a) lipoprotein concentrations did not differ between the two groups. The resistance of low density lipoprotein to oxidation was lower in the men from Vilnius; lag phase was 67.6 v 79.5 minutes (P < 0.001). Also lower in the men from Vilnius were mean plasma concentrations of lipid soluble antioxidant vitamins (beta carotene 377 v 510 nmol/l, P < 0.01; lycopene 327 v 615 nmol/l, P < 0.001; and lipid adjusted gamma tocopherol 0.25 v 0.46 mumol/mmol, P < 0.001. alpha Tocopherol concentration did not differ). Regression analysis showed that the lag phase was still significantly shorter by 10 minutes in men from Vilnius when the influence of other known factors was taken into account. CONCLUSIONS: The high mortality from coronary heart disease in Lithuania is not caused by traditional risk factors alone. Mechanisms related to antioxidant state may be important.


Assuntos
Antioxidantes/metabolismo , Doença das Coronárias/mortalidade , Pressão Sanguínea/fisiologia , Peso Corporal , Colesterol/sangue , Doença das Coronárias/metabolismo , Doença das Coronárias/fisiopatologia , Estudos Transversais , Humanos , Lituânia/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suécia/epidemiologia , Triglicerídeos/sangue , Vitaminas/metabolismo
11.
Curr Opin Lipidol ; 6(6): 369-73, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8750250

RESUMO

The Scandinavian Simvastatin Survival Study showed that a 35% decrease in LDL-cholesterol was accompanied by a 42% reduction in coronary mortality. Even if the period of time is longer than 1 year for the divergence of survival curves in the simvastatin and placebo groups there are reasons to believe that the beneficial effect of lipid lowering is rapid. The effect may be mediated by stabilization of lipid-rich coronary lesions or by effects on endothelium. Lipid-lowering studies in the acute stage of coronary heart disease are suggested.


Assuntos
Anticolesterolemiantes/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , LDL-Colesterol/sangue , Ensaios Clínicos como Assunto , Doença das Coronárias/metabolismo , Doença das Coronárias/mortalidade , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/metabolismo , Infarto do Miocárdio/prevenção & controle , Países Escandinavos e Nórdicos
12.
Scand J Dent Res ; 102(5): 299-305, 1994 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-7817155

RESUMO

Analysis and treatment of dental and medical factors that can cause burning mouth were performed in 25 consecutive patients according to a treatment protocol. The effect of the dental and medical treatment on the burning mouth was evaluated. The sick leave profile was presented. Apart from burning mouth symptoms, the patients reported several oral and general symptoms, such as gustatory changes, xerostomia, back and joint muscle pain, headache, and dizziness. The most common dental diagnoses were temporomandibular joint, masticatory, and tongue muscle dysfunction and lesions in the oral mucosa. The most common medical diagnoses were low serum iron and hypersensitive reaction to mercury. None of the patients tested exceeded the limit of 100 nmol Hg/l urine. Replacement of amalgam fillings was the most common dental therapy, followed by treatment of dysfunction in the masticatory system. Iron replacement was the most frequent medical treatment. The patients had over 50% more days per year sick leave than an age- and sex-matched normal population. A follow-up found that the burning mouth had disappeared in 32% of the patients. This study confirms the opinion that burning mouth is multicausal. Hypersensitive reaction to mercury was more frequent than expected, but replacement of amalgam fillings relieved burning mouth in only two of five such patients, and one of these two patients had hypersensitive reactions to both mercury and gold. One reason that so many patients continued to have burning mouth might have been neglect of dental, medical, or both diagnoses. Another reason might be that assessment of the psychologic status of the patients and psychologic treatment when indicated were not done.


Assuntos
Síndrome da Ardência Bucal/etiologia , Absenteísmo , Adulto , Idoso , Dor nas Costas/fisiopatologia , Síndrome da Ardência Bucal/diagnóstico , Síndrome da Ardência Bucal/fisiopatologia , Síndrome da Ardência Bucal/terapia , Restauração Dentária Permanente/efeitos adversos , Tontura/fisiopatologia , Feminino , Seguimentos , Ligas de Ouro/efeitos adversos , Cefaleia/fisiopatologia , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/etiologia , Ferro/sangue , Articulações/fisiopatologia , Masculino , Músculos da Mastigação/fisiopatologia , Mercúrio/efeitos adversos , Mercúrio/urina , Pessoa de Meia-Idade , Doenças da Boca/diagnóstico , Músculos/fisiopatologia , Doenças Musculares/diagnóstico , Doenças Musculares/terapia , Dor/fisiopatologia , Distúrbios do Paladar/fisiopatologia , Transtornos da Articulação Temporomandibular/diagnóstico , Xerostomia/fisiopatologia
13.
J Dermatol Surg Oncol ; 19(3): 225-7, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8445106

RESUMO

BACKGROUND: The problem with all bipolar diathermy equipment is the adherence of the tissue to the prongs of the forceps. OBJECTIVE AND METHODS: We describe a new computerized bipolar coagulator (Coa-Comp/M) with electronic feedback of the tissue impedance that automatically starts and shuts off coagulation thus preventing overheating, undue tissue damage and sticking of the forceps. The fully automation implies that no footswitch or handcontrol is necessary. The coagulator was tested during 2 years in advanced dermatologic surgery. RESULTS: A log memory recorded the number of coagulations according to effect and coagulation time. A power setting of 16W was appropriate for effective coagulation of most vessels; 99% of the coagulations were faster than 1.3 seconds necessitating automatic control for preventing sticking and charring. CONCLUSIONS: The automatic bipolar coagulator saves time and avoids sticking of the forceps. It is a useful tool in dermatologic surgery demanding repeated coagulations for hemostasis.


Assuntos
Dermatologia/instrumentação , Eletrocoagulação/instrumentação , Microcomputadores , Terapia Assistida por Computador , Desenho de Equipamento , Estudos de Avaliação como Assunto , Humanos
15.
J Neurosurg ; 75(1): 148-51, 1991 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2045902

RESUMO

A new computerized bipolar coagulator is described in which tissue heating is switched off automatically when adequate vessel occlusion has been achieved, thus preventing overheating, undue tissue damage, cutting, and sticking of the forceps. Experiments with radiofrequency (rf) heating of albumin or arteries revealed an impedance minimum at the moment of coagulation. The attainment of this impedance minimum is transmitted electronically via a microprocessor to the coagulator, which automatically shuts off the rf energy supply. In experiments, adequate artery strength and avoidance of the drawbacks of conventional coagulation methods were achieved when rf heating was shut off soon after the impedance minimum was reached. Neither irrigation for cooling nor cleaning of the forceps tips was necessary. Electronic feedback through the same cables as used for coagulation enabled the use of conventional bipolar cables and forceps. The bipolar coagulator described can also be used for conventional bipolar coagulation under visual control. The microcomputer enables: 1) automatic coagulation cycles that start when tissue is picked up in the forceps and stop automatically on completion of the seal; 2) the change of power setting from a pedal and activation of automatic cycles by the pedal as described above or surgeon-controlled coagulation, which facilitates the use of alternative debridement with inactive forceps; 3) cable testing; and 4) negligible disturbance of the intraoperative monitoring equipment.


Assuntos
Eletrocoagulação/instrumentação , Animais , Artérias/patologia , Artérias/fisiologia , Condutividade Elétrica , Desenho de Equipamento , Técnicas In Vitro , Monitorização Fisiológica , Suínos
18.
Klin Wochenschr ; 66(11): 494-7, 1988 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-2841535

RESUMO

Plasma levels of cyclic nucleotides were determined by radioimmunoassay in patients with (1) angina-like chest pain and normal coronary arteries (suspected spasm angina), (2) exercise-induced angina, and (3) heart diseases other than angina pectoris, as well as in (4) normal subjects. The concentration of cyclic GMP in plasma was significantly lower (by at least three-fold) in patients with suspected spasm angina, as compared with the other groups. No statistically significant difference in the plasma levels of cAMP was observed between the different patient groups. The low cGMP levels in plasma from patients with angina-like chest pain and normal coronary arteries might be an indication of a defect in the vasculature, making it more sensitive to contractile stimuli.


Assuntos
Angina Pectoris/sangue , Angiografia Coronária , Doença das Coronárias/sangue , Vasoespasmo Coronário/sangue , GMP Cíclico/sangue , Adulto , Angina Pectoris/diagnóstico por imagem , Doença das Coronárias/diagnóstico por imagem , Vasoespasmo Coronário/diagnóstico por imagem , AMP Cíclico/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Acta Med Scand ; 223(4): 313-20, 1988.
Artigo em Inglês | MEDLINE | ID: mdl-2835890

RESUMO

Enalapril 40 mg or tolerated dose was given once daily to 21 patients with congestive heart failure (CHF), NYHA class III, in addition to treatment with digoxin and/or diuretics. After an 8-week open period, 19 patients were randomized to continue enalapril or to receive a placebo in a double-blind manner. After the first enalapril dose of 10 mg, maximal reduction of blood pressure (BP) occurred after 4 hours (mean 34/17 mmHg; p less than 0.001). No further reduction was found after higher doses. After the open period significant improvement was shown as judged by NYHA class (p less than 0.01), stroke volume (p less than 0.05), maximal working capacity (p less than 0.05), heart volume (p less than 0.01) and maximum rate pressure product (RPPmax) (p less than 0.001). Urinary aldosterone markedly decreased (p less than 0.01), whereas serum potassium and serum creatinine slightly increased (p less than 0.05). At the end of the blind period enalapril was superior to placebo concerning NYHA class (p less than 0.01), heart volume (p less than 0.05) and RPPmax (p less than 0.05). Other parameters, including aldosterone in urine, did not differ between the groups. Carry-over effects may have diminished the differences between enalapril and placebo. Diarrhoea (n = 5) and hypotension (n = 5) were the most common side-effects. Overall, enalapril was well tolerated and seems to be useful in single daily doses in the treatment of CHF.


Assuntos
Enalapril/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Adulto , Idoso , Ensaios Clínicos como Assunto , Método Duplo-Cego , Enalapril/efeitos adversos , Enalapril/metabolismo , Feminino , Meia-Vida , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Pharm Biomed Anal ; 5(8): 767-75, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-16867452

RESUMO

Factors that affect the standardization and reliability of the radioimmunoassay of digoxin are reviewed. Some new data are presented on standardization and suggestions are made for dealing with problems in the design and techniques of assays.

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