Lymphocyte P-glycoprotein variability in healthy individuals / Variabilidad de la glicoproteína P linfocitaria en una población sana

The aim of the present work was to describe the distribution of lymphocyte P-glycoprotein activity on a population of healthy individuals, taking also into account sex and age. P-glycoprotein activity in lymphocytes was measured by the Rhodamine 123 efflux assay using flow cytometry, in the presence and absence of verapamil, a P-glycoprotein inhibitor. We obtained a range of P-glycoprotein activity from 1.04 to 3.79. The distribution of the activity in the population studied was better described by a bimodal model, according with the Kolmogorov-Smirnov test. The frequency adjusted to the following equation: F = 0.70 N (2.11; 0.43) + 0.30 N(3.29; 0.26), in which 0.70 and 0.30 represented the proportion of each group, and 0.43 and 0.26 were the standard deviations of the activity of each group, respectively. The study of the relationship between subjects´ age and P-glycoprotein activity showed no statistical significance. When healthy volunteers were separated according to sex, similar distributions were observed, although for men an increase in proportion of higher P-glycoprotein function group was observed. The variability observed in the population studied was important, with some volunteers with very scarce activity and some with a fourfold higher activity. Characterization of P-glycoprotein functionality in the population represents a useful contribution to the beginning of pharmacological treatments that consider its effect on pharmacokinetics and pharmacodynamics of individualized patients.

El objetivo del presente trabajo fue describir la distribución de la actividad de la glicoproteína P linfocitaria en una población de individuos sanos, considerando a su vez el sexo y la edad. La funcionalidad de la glicoproteína P fue determinada mediante el ensayo de eflujo de Rodamina 123, en presencia y ausencia de verapamilo, un inhibidor competitivo de este transportador, determinando la fluorescencia intracelular remanente mediante citometría de flujo. Obtuvimos un rango de actividades de entre 1.04 y 3.79. La distribución de la actividad en la población evaluada se ajusta a un modelo bimodal, según el test de Kolmogorov-Smirnov. La frecuencia ajusta a la siguiente ecuación: F = 0.70 N (2.11; 0.43) + 0.30 N (3.29; 0.26) donde 0.70 y 0.30 representan las proporciones de cada grupo, mientras que 0.43 y 0.26 corresponden al desvío estándar de la actividad de cada grupo respectivamente. Al estudiar la correlación entre la edad de los sujetos y la función de la proteína, no se observaron diferencias significativas. Cuando los individuos fueron clasificados en función del sexo, las distribuciones obtenidas fueron semejantes, aunque para los varones se observó un aumento en la proporción de individuos con alta actividad. La variabilidad observada fue importante, comprendiendo individuos con escasa actividad y otros que presentaron una actividad hasta cuatro veces mayor. La caracterización de la función de la glicoproteína P en la población representa una contribución indispensable para el desarrollo de tratamientos farmacológicos personalizados que consideren el efecto de dicho transportador en la farmacocinética y farmacodinámica de cada paciente.

Utilidad de la prueba de coaglutinación (phadebact) en el diagnóstico etiológico de neumonía adquirida en la comunidad en niños: Hospital Central de San Cristobal período julio-septiembre 2000 / Utility of the prueba od coaglutiation (phadebact) in the diagnostic etiologic of neumoniae adquired in the community in clhildren: Hospital Central de San Cristobal period julio-september 2000

Determinar la utilidad de la prueba phadebact en la etiología de Neumonia Adquirida en la comunidad en niños. Estudio prospectivo, descriptivo y transversal con una población de 30 niños con edad entre 2-11 años, diagnóstico clínico-epidemiológico de NAC. Se practico la prueba de Coaglutinación (Phadebact): NAC fue más frecuente en la edad preescolar (33.3 por ciento), predomino el sexo masculino (60 por ciento). El phadebact fue positivo en 5 niños (16,6 por ciento). Conclusión: la prueba de Coaglutinación posee baja especificidad en el diagnóstico de NAC. Se recomienda como método

Acquisition of methicillin resistance and progression of multiantibiotic resistance in methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) produces specific penicillin-binding protein, PBP2', which shows remarkably low affinities to most beta-lactam antibiotics except those such as penicillin G and ampicillin. The region surrounding mecA has been called additional DNA or mec and is thought to be of extraspecies origin. From the study of mec, we found that mec is a novel mobile genetic element and designated as staphylococcal cassette chromosome mec (SCCmec). There are three types of SCCmec. In the past decades, MRSA has become resistant to many antibiotics, such as carbapenems, new quinolones, and minocycline etc. It seems to be a characteristic of MRSA to acquire multi-resistance by accumulating multiple resistance genes around the mecA gene inside SCCmec.

Emergence and spread of antimicrobial resistance of Streptococcus pneumoniae in Korea

Pneumococcal resistance has become a global issue during the past three decades. One of the major foci of pneumococcal resistance worldwide is the Asian region including Korea, Japan, and Hong Kong. Korea had not been recognized as a focus of pneumococcal resistance until 1995, when serial reports documented the alarmingly high prevalence of penicillin resistance among clinical isolates. Serial reports on penicillin resistance among pneumococcal isolates in Korea ranged from 68% to 77% as of 1995. Multidrug resistance was also noted in 34% of Korean isolates. Penicillin-binding protein profile analysis, pulsed-field gel electrophoresis, ribotyping, and fingerprinting analysis of pbp genes showed that antibiotic-resistant pneumococci isolated in Korea were genetically related. Data documented the extensive spread of a resistant clone within Korea and between different countries. Besides the injudicious use of antimicrobial agents or the high prevalence of serotypes 23 and 19, the spread of a resistant clone may play an important role in the rapid increase of penicillin resistance in Korea.

Suppression of multidrug resistance via inhibition of heat shock factor by quercetin in MDR cells

MDR1 promoter has been shown to contain heat shock elements (HSE), and it has been reported that FM3A/M and P388/M MDR cells show a constitutively activated heat shock factor (HSF), suggesting that HSF might be an important target for reversing the multidrug resistance. Therefore, it was examined whether quercetin, which has been shown to interfere with the formation of the complex between HSE and HSF, and to downregulate the level of HSF1, can sensitize MDR cells against anticancer drugs by inhibition of HSF DNA-binding activity. In this study, quercetin appeared to inhibit the constitutive HSF DNA-binding activity and the sodium arsenite-induced HSF DNA-binding activity in the MDR cells. The basal and sodium arsenite-induced MDRCAT activities were remarkably suppressed by the treatment of quercetin. These results were well consistent with the finding that the treatment of quercetin decreased the expression level of P-gp, MDR1 gene product, in dose-dependent manner, and markedly increased the sensitivity of MDR cells to vincristine or vinblastine. These results suggest that quercetin can decrease the expression of P-gp via inhibition of HSF DNA-binding activity, and might be useful as a chemosensitizer in MDR cells.

Resistência a múltiplas drogas: um problema da clínica oncológica com soluçäo na pesquisa básica / Multidrug resistence: a problem of the oncology clinics with solution in basic research

A resistência que as células neoplásicas apresentam aos agentes quimioterápicos sempre é um grande problema para o oncologista clínico. A descoberta da glicoproteína (170 Pgp) responsável pela resistência a múltiplas drogras (MDR) abriu novas perspectivas de se superar este difícil tipo de resistência. Neste trabalho, apresentamos uma retrospectiva do trabalho de pesquisa realizado até a definiçäo do modelo que hoje rege os trabalhos clínicos no emprego de agentes reversores de MDR.