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1.
Rev Esp Quimioter ; 33(1): 49-67, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31933347

RESUMO

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent diseases in the World, and one of the most important causes of mortality and morbidity. In adults 40 years and older, it affects more than 10% of the population and has enormous personal, family and social burden. Tobacco smoking is its main cause, but not the only one, and there is probably a genetic predisposition that increases the risk in some patients. The paradigm of this disease is changing in Spain, with an increase of women that has occurred in recent years. Many of the physio pathological mechanisms of this condition are well known, but the psychological alterations to which it leads, the impact of COPD on relatives and caregivers, the limitation of daily life observed in these patients, and the economic and societal burden that they represent for the health system, are not so well-known. A major problem is the high under-diagnosis, mainly due to difficulties for obtaining, in a systematic way, spirometries in hospitals and health-care centers. For this reason, the Fundación de Ciencias de la Salud and the Spanish National Network Center for Research in Respiratory Diseases (CIBERES) have brought together experts in COPD, patients and their organizations, clinical psychologists, experts in health economics, nurses and journalists to obtain their opinion about COPD in Spain. They also discussed the scientific bibliometrics on COPD that is being carried out from the CIBERES and speculated on the future of this condition. The format of the meeting consisted in the discussion of a series of questions that were addressed by different speakers and discussed until a consensus conclusion was reached.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Ansiedade/etiologia , Bibliometria , Pesquisa Biomédica , Meios de Comunicação , Efeitos Psicossociais da Doença , Depressão/etiologia , Família , Feminino , Humanos , Masculino , Cuidados de Enfermagem , Cooperação do Paciente , Participação do Paciente , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/economia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/prevenção & controle , Pneumologia/educação , Anos de Vida Ajustados por Qualidade de Vida , Fatores Sexuais , Licença Médica/economia , Fumar/efeitos adversos , Fumar/epidemiologia , Abandono do Hábito de Fumar , Espanha/epidemiologia , Espirometria , Poluição por Fumaça de Tabaco/efeitos adversos
2.
Forensic Sci Int ; 172(2-3): 211-7, 2007 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-17320328

RESUMO

Haplotype frequencies for 16 Y-chromosomal short tandem repeat (STR) loci, included in the Y-Filer kit, were determined in 247 unrelated healthy individuals from the Barcelona metropolitan area (Catalonia, NE Spain). After PCR amplification and denaturing PAGE electrophoresis, DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4.1, DYS437, DYS438 and DYS448 loci were typed. The aim of this study is to evaluate the performance in our population of the 16 loci of the Y-chromosome present in the new Y-Filer commercial identification kit, and acquire haplotype frequencies for mathematic processing of the forensic diagnosis in our geographical working area. In this sample, all haplotypes were unique. From the forensic point of view, the combined polymorphisms of the Y-Filer kit provide a high diagnostic efficiency.


Assuntos
Impressões Digitais de DNA/métodos , Frequência do Gene , Genes Ligados ao Cromossomo Y/genética , Haplótipos , Repetições de Microssatélites/genética , Bases de Dados de Ácidos Nucleicos , Variação Genética , Humanos , Masculino , Espanha , População Urbana
3.
Forensic Sci Int ; 168(1): e10-2, 2007 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-17321706

RESUMO

Haplotype frequencies for 16 Y-chromosomal short tandem repeat (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635, DYS392, Y GATA H4, DYS437, DYS438 and DYS448) loci, included in the AmpFLSTR Yfiler PCR Amplification Kit, were analysed in 110 Fang and 133 Bubi individuals from Bioko Island, Equatorial Guinea. The diversity was higher in Fang population, probably since they were originally from the mainland, with which they maintain tribal village and family links, and to which they travel frequently. Comparisons were made with previously published haplotype data on European and African populations, and significant differences were found between them.


Assuntos
Cromossomos Humanos Y , Genética Populacional , Haplótipos , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Guiné Equatorial , Frequência do Gene , Humanos , Masculino , Reação em Cadeia da Polimerase
4.
Forensic Sci Int ; 166(2-3): 230-2, 2007 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-16436322

RESUMO

The 15 AmpF/STR Identifiler loci (D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818 and FGA) were analyzed in the sample of 180 unrelated autochthonous healthy adults born in Meztitlán City from the valley of Metztitlán (Estado de Hidalgo, México). The agreement with Hardy-Weinberg equilibrium was confirmed for all loci. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.


Assuntos
Frequência do Gene , Genética Populacional , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Cabelo/química , Humanos , México , Reação em Cadeia da Polimerase
5.
Int J Legal Med ; 119(2): 107-10, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15565295

RESUMO

Allele frequencies for 15 STR loci (D8S1179, D21S11, D7S820, CSF1PO, D19S433, HUMVWA31A, HUMTPOX, D18S51, D3S1358, HUMTHO1, D13S317, D16S539, D2S1338, D5S818 and HUMFGA) were analysed in the Fang population of Bioko Island, Equatorial Guinea. No deviation from Hardy-Weinberg equilibrium was found for all loci. Statistical parameters demonstrated the forensic utility of the analysed systems.


Assuntos
Frequência do Gene , Genética Populacional , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Guiné , Humanos , Reação em Cadeia da Polimerase , Polimorfismo Genético
6.
Int J Legal Med ; 119(2): 111-5, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15378309

RESUMO

The purpose of this study is to report allele frequency data of three ethnic Amerindian population samples: the Otomi (Hna-hnu) from eastern Sierra Madre and Ixmiquilpan valley and the Huasteco from La Huasteca. These groups were characterised by 15 STR-PCR polymorphisms (HumTH01, HumvWA, D18S51, HumTPOX, D19S433, D16S539, D13S317, D8S1179, D7S820, D5S818, HumFGA, CSF1PO, D2S1338, D3S1358 and D21S11). No significant deviations in observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the studied systems. From the forensic point of view, the heterozygosity value, power of discrimination and the a priori chance of exclusion were calculated.


Assuntos
Etnicidade/genética , Frequência do Gene , Genética Populacional , Polimorfismo Genético , Sequências de Repetição em Tandem , Impressões Digitais de DNA , Humanos , México , Reação em Cadeia da Polimerase
8.
Int Immunopharmacol ; 3(7): 987-99, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12810356

RESUMO

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.


Assuntos
Ciclosporina/farmacologia , Ciclosporina/farmacocinética , Imunossupressores/farmacologia , Imunossupressores/farmacocinética , Transplante de Rim/imunologia , Área Sob a Curva , Disponibilidade Biológica , Calcineurina/metabolismo , Ciclosporina/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Imunossupressores/administração & dosagem , Interferon gama/sangue , Interleucina-2/sangue , Masculino , Pessoa de Meia-Idade
9.
J Agric Food Chem ; 51(10): 3191-5, 2003 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-12720414

RESUMO

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a variety of materials, including synthetic polymers and textiles. Although these chemicals have been detected in environmental samples and human tissues, there is little information about human exposure to PBDEs through the diet. In the present study, we determined the concentrations of PBDEs in a number of food samples acquired in Catalonia (Spain) during 2000. The dietary intake of PBDEs was estimated for the general population living in this Spanish region. The highest PBDE concentrations were found in oils and fats, fish and shellfish, meat and meat products, and eggs, while the lowest levels corresponded to fruits, vegetables, and tubers. The dietary intake of PBDEs for an adult male was 97.3 ng/day (assuming not detected (ND) = (1)/(2) limit of detection (LOD)) or 81.9 ng/day (assuming ND = 0) The greatest contribution to these values corresponded to fish and shellfish, with approximately one-third of the total intake. TetraBDEs and pentaBDEs were the homologues showing the highest percentages of contribution to the sum of total PBDEs. The comparison of the current dietary intake with the suggested lowest observed adverse effect level value of 1 mg/kg/day for the most sensitive endpoints for toxic effects of PBDEs results in a safety factor over 5 orders of magnitude in relation to PBDE exposure from food.


Assuntos
Dieta , Exposição Ambiental , Análise de Alimentos , Bifenil Polibromatos/análise , Adulto , Animais , Gorduras na Dieta/análise , Gorduras Insaturadas na Dieta/análise , Ovos/análise , Éteres/análise , Peixes , Frutas/química , Humanos , Masculino , Carne/análise , Produtos da Carne/análise , Frutos do Mar/análise , Espanha , Verduras/química
11.
Arch Environ Contam Toxicol ; 43(4): 461-5, 2002 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-12399917

RESUMO

Emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) by municipal solid waste (MSW) incinerators cause concern to the populations living in the vicinity of these facilities. In this study, the health risks of PCDD/F exposure were assessed for adults and children living 500 and 1,000 m from the MSW incinerator. A comparative analysis was performed before (1998) and after (2000) pronounced decreases in PCDD/F air emissions from the stack were noted as a consequence of technical improvements in the facility. At 500 m, total environmental exposure to PCDD/Fs diminished from 5.102 x 10(-5) to 1.271 x 10(-5) ng I-TEQ/kg/day for adults, and from 8.131 x 10(-5) to 2.656 x 10(-5) ng I-TEQ/kg/day for children, which means a reduction of 75.1% for adults and 67.3% for children between 1998 and 2000. At 1,000 m, total environmental PCDD/F exposure diminished from 4.087 x 10(-5) ng I-TEQ/kg/day in 1998 to 0.995 x 10(-5) ng I-TEQ/kg/day in 2000 and from 6.294 x 10(-5) ng I-TEQ/kg/day in 1998 to 1.983 x 10(-5) ng I-TEQ/kg/day in 2000 for adults and children, respectively. However, these reductions are almost imperceptible compared with the contribution of dietary intake of PCDD/F to total exposure to these contaminants. The present results corroborate that for MSW incinerators with modern technologies, human PCDD/F exposure is mainly due to background contamination.


Assuntos
Benzofuranos/efeitos adversos , Exposição Ambiental , Modelos Teóricos , Dibenzodioxinas Policloradas/análogos & derivados , Dibenzodioxinas Policloradas/efeitos adversos , Saúde Pública , Eliminação de Resíduos , Poluentes do Solo/efeitos adversos , Adolescente , Adulto , Poluentes Atmosféricos/análise , Benzofuranos/análise , Criança , Dibenzofuranos Policlorados , Contaminação de Alimentos , Humanos , Incineração , Pessoa de Meia-Idade , Dibenzodioxinas Policloradas/análise , Medição de Risco , Poluentes do Solo/análise
12.
Sci Total Environ ; 289(1-3): 237-41, 2002 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-12049399

RESUMO

Serum manganese levels were determined in 250 healthy subjects (122 men and 128 women) living in Barcelona in northeastern Spain. The study was designed to assess the reference levels for serum manganese and to investigate its relationship to age and sex. The age distribution ranged from 15 to 90 years. The assays were performed by means of a graphite furnace atomic absorption spectrometry. The geometric mean of serum manganese concentration was 1.1 microg/l, ranging from 0.3 microg/l to 2.5 microg/l. In almost every case, the 95th upper percentiles of this element were < 1.8 microg/l. No correlation between the concentration of manganese and sex could be established, but in the younger population the manganese levels were nearly three times higher than the results obtained in the older population.


Assuntos
Monitoramento Ambiental , Manganês/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Espanha , População Urbana
13.
Arch Environ Contam Toxicol ; 42(1): 93-8, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11706373

RESUMO

The development toxicity of lead nitrate (25 mg/kg, SC), methylmercury chloride (12.5 mg/kg, PO), and sodium arsenite (6 mg/kg, SC) was assessed in CD1 mice following administration on gestation day 10 of these chemicals separately or in their binary and ternary combinations. Cesarean sections were performed on day 18 of gestation, and fetuses were examined for malformations and variations. Three fetuses from each dam were used for whole-body analyses of Pb, Hg, and As. Maternal toxic effects were more remarkable in the group concurrently exposed to Pb, Hg, and As than in those given binary combinations of the elements. In turn, maternal toxicity was more notable in these groups than in those given separately the test compounds. With regard to developmental toxicity, the most relevant effects (decreased fetal weight, cleft palate) corresponded to the Hg-treated groups. It is in agreement with the finding that in all experimental groups the levels of Pb and As in whole fetuses were under their respective detection limits. In general terms, the present data suggests that at the current doses, the interactive effects of Pb and As on Hg-induced developmental toxicity were not greater than additive. In contrast, exposure of pregnant mice to Pb and As at doses that were practically nontoxic to dams, concurrently with organic Hg at a toxic dose, caused supra-additive interactions in maternal toxicity.


Assuntos
Arsênio/efeitos adversos , Fissura Palatina/induzido quimicamente , Chumbo/efeitos adversos , Troca Materno-Fetal , Mercúrio/efeitos adversos , Administração Oral , Animais , Arsênio/farmacologia , Peso ao Nascer , Fissura Palatina/veterinária , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Injeções Subcutâneas , Chumbo/farmacologia , Dose Letal Mediana , Mercúrio/farmacologia , Camundongos , Gravidez , Distribuição Tecidual
14.
Artigo em Inglês | MEDLINE | ID: mdl-11688690

RESUMO

The concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V) and zinc (Zn) were determined in autopsy tissues collected from subjects who at the time of death had lived in Tarragona (Catalonia, Spain) over a period of, at least, the previous 10 years. Samples of liver, lung, kidney, brain and bone were obtained from a total of 78 non-occupationally exposed subjects, autopsied between 1997 and 1999. Arsenic, Cd, Co, Cr, Cu, Pb, Mn, Hg, Ni, Sn, V and Zn were determined by inductively coupled plasma spectrometry (ICP/MS). The results were analyzed with respect to age, sex, smoking and drinking habits, and the subject's place of residence. Most tissue concentrations of As, Co, Cr, Hg and V were near to the analytical detection limit or, in some cases, even below it. However, the levels of Cu were slightly higher than the average concentrations found in other studies. Also, tissue concentrations of Mn, Sn and Zn were similar to those found in previous surveys, while those of Ni were lower than previously reported. Although the current levels of tissue Cd and Pb were comparatively lower than in studies in other areas, the distribution of both metals was similar to previously-reported trends. From the tissue metal concentrations observed in the present study, it would appear that neither environmental exposure nor a dietary excess of these elements could be considered a health hazard to people living in the study area.


Assuntos
Arsênio/farmacocinética , Exposição Ambiental , Metais Pesados/farmacocinética , Fatores Etários , Autopsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Fatores Sexuais , Espanha , Distribuição Tecidual
15.
Cancer Lett ; 173(2): 155-62, 2001 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-11597790

RESUMO

Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8-diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-->113His (exon 3) and 139His-->139Arg (exon 4). We performed a case-control study among Northwestern Mediterranean Caucasians to investigate a possible association between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were analyzed in a group of lung cancer patients (n=176) and in a control group of healthy smokers (n=187). The results showed a significantly decreased risk for the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33-0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His, respectively, as the references. Thereafter, we analyzed the EPHX1 variants in combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1, and GSTP1) and we found a significant overepresentation of cancer patients with a combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1 (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of GSTP1 results in a Ile-->Val substitution, and the isoleucine GSTpi isoform has been found in vitro to be less active than the valine isoform towards the conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. Our results agree with these observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.


Assuntos
Predisposição Genética para Doença , Neoplasias Pulmonares/genética , Polimorfismo Genético , Adulto , Idoso , Idoso de 80 Anos ou mais , Epóxido Hidrolases/genética , Éxons , Feminino , Genótipo , Glutationa Transferase/metabolismo , Histidina/química , Homozigoto , Humanos , Masculino , Microssomos/metabolismo , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Isoformas de Proteínas , Fumar , Tirosina/química
16.
Int J Legal Med ; 114(4-5): 298-300, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11355417

RESUMO

Allele frequencies for eight STR loci (HUMTH01, HUMVWA31A, HUMCSF1PO, HUMTPOX, D3S1358, D8S1179, D18S51, D19S253) have been analysed in the Bubi population of Bioko Island, Equatorial Guinea. For all loci, no deviation from Hardy-Weinberg equilibrium was found. Data obtained were compared with that of Caucasian and African populations. Significant differences were found for all systems between all the black populations compared and the Caucasoid population. Similarities were observed between the Bubi and Zimbabweans, and also with African American populations. Also, more affinities were observed between Zimbabweans and Ugandans and Ovambos than between these groups and the Bubi population. From these comparisons it is suggested that in Africa, as in other continents, there is a certain genetic heterogeneity.


Assuntos
Impressões Digitais de DNA , Polimorfismo Genético , Sequências de Repetição em Tandem , População Negra/genética , Guiné Equatorial , Frequência do Gene , Heterogeneidade Genética , Genótipo , Humanos
17.
Biol Trace Elem Res ; 79(1): 67-81, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11318238

RESUMO

The present study was conducted to assess in rats the effects of oral aluminum (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) accumulation and urinary excretion. Three groups of plug-positive Sprague-Dawley (SD) rats were given by gavage 0, 200, and 400 mg/kg/d of Al(OH)3 on gestational days 1-20. Three groups of nonpregnant female SD rats of the same age received Al(OH)3 by gavage at the same doses for 20 consecutive days. At the end of the treatment period, 24-h urine samples were collected for analysis of Al and essential elements. Subsequently, all animals were sacrificed and samples of liver, bone, spleen, kidneys, and brain were removed for metal analyses. With some exceptions, the urinary amounts of Al, Mn, and Cu excreted by pregnant animals as well as the urinary levels of Al excreted by nonpregnant rats were higher in the Al-treated groups than in the respective control groups. Although higher Al levels were found in the liver of pregnant rats, the concentrations of Al in the brain of these animals were lower than those found in the same tissues of nonpregnant rats. With regard to the essential elements, tissue accumulation was most affected in pregnant than in nonpregnant animals. In pregnant rats, the hepatic and renal concentrations of Ca, Mg, Mn, Cu, Zn, and Fe, as well as the levels of Ca in bone, and the concentrations of Cu in brain were significantly higher in the Al-exposed groups than in the control group. According to the current results, oral Al exposure during pregnancy can produce significant changes in the tissue distribution of a number of essential elements.


Assuntos
Alumínio/farmacologia , Oligoelementos/metabolismo , Alumínio/sangue , Alumínio/metabolismo , Alumínio/urina , Animais , Osso e Ossos/metabolismo , Encéfalo/metabolismo , Cobre/sangue , Cobre/urina , Relação Dose-Resposta a Droga , Feminino , Ferro/sangue , Ferro/urina , Rim/metabolismo , Fígado/metabolismo , Manganês/sangue , Manganês/urina , Gravidez , Ratos , Ratos Sprague-Dawley , Baço/metabolismo , Fatores de Tempo
19.
Transpl Int ; 13 Suppl 1: S301-5, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11112019

RESUMO

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.


Assuntos
Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Adolescente , Adulto , Idoso , Área Sob a Curva , Ciclosporina/uso terapêutico , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Seguimentos , Humanos , IMP Desidrogenase/sangue , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/sangue , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Fatores de Tempo
20.
Ther Drug Monit ; 22(5): 621-5, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11034270

RESUMO

The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates containing butalbital as internal standard were separated with a 7-microm Chromsystems C18 250 x 4.0 mm I.D. reversed-phase column at a temperature of 40 degrees C using a mobile phase consisting of pH 3.8 phosphate-acetonitrile buffer (55:45, v/v), at a flow rate of 0.8 mL/min. Ultraviolet detection was carried out at 210 nm. Measurement of the peak:height ratio allowed quantitative determination of the samples. The method was linear over a concentration range of 0.2 to 20 microg/mL for lamotrigine. Recovery was >90%. Within-day and between-day coefficients of variation ranged from 1.8% to 6.7%. The mean lamotrigine concentration was 8.01 +/- 5.63 microg/mL. After studying sera from 130 patients treated with lamotrigine the authors confirmed that associated antiepileptic therapy affected the serum lamotrigine levels, which were significantly higher in patients under valproic acid treatment.


Assuntos
Anticonvulsivantes/sangue , Cromatografia Líquida de Alta Pressão/normas , Monitoramento de Medicamentos/normas , Epilepsia/tratamento farmacológico , Triazinas/sangue , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Esquema de Medicação , Quimioterapia Combinada , Epilepsia/sangue , Feminino , Humanos , Lamotrigina , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Triazinas/administração & dosagem , Triazinas/farmacocinética
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