RESUMO
Objective. To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE) in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods. Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF-α, IFN-γ, IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone. Results. Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups. Conclusion. DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP).
Assuntos
Doenças Autoimunes/tratamento farmacológico , Inflamação/tratamento farmacológico , Prostatite/tratamento farmacológico , Fator de Transferência/administração & dosagem , Animais , Doenças Autoimunes/sangue , Doenças Autoimunes/patologia , Dexametasona , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/sangue , Inflamação/patologia , Interleucina-17/biossíntese , Interleucina-4/biossíntese , Interleucina-6/biossíntese , Antígenos Comuns de Leucócito/biossíntese , Masculino , Camundongos , Prostateína/sangue , Hiperplasia Prostática/sangue , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Prostatite/sangue , Prostatite/patologia , Ratos , Fator de Necrose Tumoral alfa/biossínteseRESUMO
INTRODUCTION: The drop-out rate among patients receiving preventive treatment for migraine is higher than 30%. This situation is not very widely known and the risk factors that lead patients to drop out from treatment have yet to be identified. AIM: To evaluate some of the factors that can predispose patients to drop out of preventive treatment. PATIENTS AND METHODS: We conducted a prospective study of patients suffering from migraine who required preventive treatment for the first time with one of what are considered the top three first-choice drugs, i.e. a beta-blocker (nadolol), a neuromodulator (topiramate) or a calcium antagonist (flunarizine). Two groups were established according to whether patients dropped out of treatment or not. Different demographic and clinical variables were analysed and compared in the two groups. RESULTS: Of 800 patients with migraine who required preventive treatment for the first time, the drop-out rate was 19.7%. In the drop-out group, the variables 'age', 'number of seizures', 'number of seizures prior to preventive treatment' and 'side effects' showed significant differences with those from the group of patients who did not drop out of preventive treatment. CONCLUSIONS: The drug used as preventive treatment, the side effects, a younger age and a lower number of seizures before starting the preventive treatment favoured higher drop-out rates. Whether the migraine was episodic or chronic, the presence of medication abuse and the drugs used to treat the seizures were not related with dropping out of preventive treatment.
Assuntos
Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Pacientes Desistentes do Tratamento , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Anticonvulsivantes/uso terapêutico , Feminino , Flunarizina/uso terapêutico , Frutose/análogos & derivados , Frutose/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Nadolol/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Satisfação do Paciente , Estudos Prospectivos , Fatores de Risco , Topiramato , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Topiramate and nadolol with levels A and C of scientific evidence, respectively, would be indicated as preventive treatments of migraine. To date only one study of satisfaction has been carried out to compare the two pharmaceuticals. AIM: To compare the effectiveness parameters in independent groups of patients treated preventively with one of the pharmaceuticals from the study. PATIENTS AND METHODS: From a database of 700 patients with migraine, those with episodic migraine and who had followed a course of preventive treatment, for the first time, with topiramate or nadolol were selected for the study. The effectiveness variables (reduction in the number of crises at four months of preventive treatment and responder rates) were analysed. RESULTS: Altogether 208 patients with were included for treatment: 140 with topiramate (77.8% females; mean age, 37.9) and 68 with nadolol (69% females; mean age, 36.9). The mean number of crises in the month prior to treatment was: topiramate group, 6.3 +/- 2.6; nadolol group 5.3 +/- 2.0 (p = 0.0066). At four months after starting treatment: topiramate group, 2.69 +/- 2.6; nadolol group 2.6 +/- 2.2 (NS). The percentage of reduction in the number of migraines was 56.6% with topiramate and 51.6% with nadolol (NS). The responder rate (reduction in the frequency of crises by at least 50%) was 71.3% with topiramate versus 69% with nadolol (NS). The excellent response rate (reduction in crises by at least 75%) was 53.3% with topiramate versus 32.2% with nadolol (p = 0.0077). Adverse side effects were reported by 54% of patients treated with topiramate versus 30.8% of those treated with nadolol (p = 0.0015). The rate of satisfaction was 61% for the topiramate group and 71% for the group with nadolol (NS). CONCLUSIONS: Both topiramate and nadolol proved to be effective in the preventive treatment of episodic migraine. Topiramate was found to be more effective than nadolol, although it was used in patients with a higher frequency of crises, and was not tolerated so well.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Frutose/análogos & derivados , Transtornos de Enxaqueca/prevenção & controle , Nadolol/uso terapêutico , Adulto , Feminino , Frutose/uso terapêutico , Humanos , Masculino , TopiramatoRESUMO
Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.
Assuntos
Eucariotos/genética , Regulação da Expressão Gênica , Entamoeba histolytica/genética , Entamoeba histolytica/metabolismo , Perfilação da Expressão Gênica/métodos , Genes de Protozoários , Genoma de Protozoário , Plasmodium/genética , Plasmodium/metabolismo , Trichomonas vaginalis/genética , Trichomonas vaginalis/metabolismo , Trypanosoma/genética , Trypanosoma/metabolismoRESUMO
The flavan-3-ol, (-)-epicatechin has been previously identified as the most important antiamoebic compound among the extracts from two medicinal plants: Rubus coriifolius and Geranium mexicanum. Here we report the effects of epicatechin on Entamoeba histolytica morphology, analyzed by electronic microscopy. E. histolytica trophozoites were incubated for 48 h at 37 degrees C in the presence of 1.9 microg/mL epicatechin and processed for electronic microscopy analysis. Epicatechin induced nuclear and cytoplasmic changes in the treated trophozoites. These morphological alterations are identical to the cellular changes experienced by E. histolytica trophozoites undergoing programmed cell death (PCD), suggesting that epicatechin could be an alternative compound to treat amoebiasis.
Assuntos
Catequina/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/ultraestrutura , Animais , Apoptose/efeitos dos fármacos , Catequina/química , Geranium/químicaRESUMO
This study presents morphological and biochemical evidence of programmed cell death (PCD) in Entamoeba histolytica induced by exposure of trophozoites to the aminoglycoside antibiotic G418. Morphological characteristics of PCD, including cell shrinkage, reduced cellular volume, nuclear condensation, DNA fragmentation and vacuolization were observed, with preservation of trophozoite membrane integrity. PCD is orchestrated biochemically by alterations in intracellular ion fluxes. In G418-treated trophozoites, overproduction of reactive oxygen species (ROS), decreased intracellular K+, increased cytosolic calcium, and decreased intracellular pH levels were observed. However, externalization of phosphatidylserine was not detected. These results suggest that amoebae can undergo PCD under stress conditions, and that this PCD shares several properties with PCD reported in mammals and in a variety of unicellular organisms.
Assuntos
Amebicidas/farmacologia , Apoptose , Entamoeba histolytica/efeitos dos fármacos , Entamoeba histolytica/fisiologia , Gentamicinas/farmacologia , Animais , Cálcio/metabolismo , Fragmentação do DNA , Entamoeba histolytica/crescimento & desenvolvimento , Entamoeba histolytica/ultraestrutura , Concentração de Íons de Hidrogênio , Estresse Oxidativo , Potássio/metabolismo , Espécies Reativas de Oxigênio , Trofozoítos/efeitos dos fármacos , Trofozoítos/fisiologiaRESUMO
BACKGROUND: The Entamoeba histolytica EhrabB gene encodes for a Rab GTPase involved in phagocytosis. It is located at a virulence locus where the Ehcp112 gene is in the complementary strand at 332 bp of EhrabB start codon, suggesting a finely regulated transcription of both genes. However, the transcription regulation in this parasite is poorly understood. RESULTS: To initiate the knowledge of EhrabB gene expression regulation, here we studied the structural characteristics of its gene promoter and its control transcription elements. In silico searches of the EhrabB 5'-flanking region revealed that it contains a motif similar to the upstream regulatory element 1 (URE1) of the E. histolytica hgl5 gene. It also has sequences with homology to C/EBP and GATA1 binding sites, and heat shock elements (HSE). Primer extension experiments revealed that EhrabB has at least four transcription initiation sites. The elements at the 5'-flanking region that drive EhrabB gene expression were detected and characterized using transitory transfected trophozoites with a plasmid carrying the CAT reporter gene. EhrabB transcription is negatively regulated by a sequence located between positions -491 to -428 with respect to the first transcription initiation site. We also showed that the URE1-like motif activates EhrabB transcription. In addition, heat shock activated the EhrabB promoter in episomal constructs and lead to an increase in de novo EhrabB transcription. CONCLUSION: The data suggest that EhrabB transcription is controlled negatively by an unidentified sequence, but it is activated by an URE1-like motif. Our analyses also revealed the presence of activator HSE that function under stress.
Assuntos
Entamoeba histolytica/enzimologia , Entamoeba histolytica/genética , Regulação Enzimológica da Expressão Gênica/genética , Regiões Promotoras Genéticas/genética , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Sequência de Aminoácidos , Animais , Cloranfenicol O-Acetiltransferase/genética , Clonagem Molecular , DNA de Protozoário/química , Ensaio de Desvio de Mobilidade Eletroforética , Fator de Transcrição GATA1 , Regulação da Expressão Gênica/fisiologia , Genes de Protozoários/fisiologia , Guanosina Trifosfato/metabolismo , Proteínas de Choque Térmico , Dados de Sequência Molecular , TATA Box , Sítio de Iniciação de Transcrição/fisiologia , Ativação Transcricional , Proteínas rab de Ligação ao GTP/químicaRESUMO
The multidrug resistance EhPgp1 gene is constitutively expressed in drug resistant trophozoites from Entamoeba histolytica. It has been demonstrated that two CCAAT/enhancer binding sites located in the EhPgp1 gene promoter control its transcriptional activation. However, functional assays of the 5' end of its promoter showed that region from -234 to -196 bp (38 bp) is also important for the EhPgp1 gene transcription. Here, we demonstrated that in the 38 bp region putative cis-activator sequences are located. In silico analysis showed the presence of GATA1, Gal4, Nit-2, and C/EBP consensus sequences. Additionally, we identified three specific DNA-protein complexes, which were competed by a C/EBP, GATA1, and HOX oligonucleotides. Finally, we partially purified three proteins of 64.4, 56.7, and 27.4 kDa. Further investigations are currently in progress to determine the identity of these nuclear factors and how they are interacting with the EhPgp1 gene promoter.
Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Entamoeba histolytica/genética , Regiões Promotoras Genéticas/fisiologia , Proteínas de Protozoários/genética , Animais , Cloranfenicol O-Acetiltransferase/genética , Cloranfenicol O-Acetiltransferase/metabolismo , Cromatografia de Afinidade , DNA de Protozoário/metabolismo , Resistência a Múltiplos Medicamentos/genética , Entamoeba histolytica/química , Proteínas Nucleares/isolamento & purificação , Proteínas Nucleares/metabolismo , Transfecção , Membro 4 da Subfamília B de Transportadores de Cassetes de Ligação de ATPRESUMO
The multidrug resistance EhPgp5 gene promoter is active in drug resistant clone C2 trophozoites and its activity increases when trophozoites are cultured in the presence of emetine, suggesting that the EhPgp5 gene shows an inducible drug dependent mechanism. We analyzed different promoter fragments to detect those regions that activate transcription in the presence of emetine. Trophozoites were transfected with p375Pgp5, p259Pgp5, p187Pgp5, and p76Pgp5 plasmids and incubated with different emetine concentrations. p375Pgp5 and p259Pgp5 plasmids were able to drive CAT expression in A and C2 trophozoites only in the presence of emetine. CAT activity was turned off in the absence of drug. Interestingly, no CAT activity was detected in the presence or in the absence of emetine with p187Pgp5 plasmid in which 59 bp were deleted at the 5' end of the EhPgp5 minimal promoter (p259Pgp5). These results suggest that the overexpression of the EhPgp5 gene is a consequence of transcriptional activation of the gene promoter by putative drug responsive elements, located within the -111 to -170 bp of the transcription initiation site.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Amebicidas/farmacologia , Emetina/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Proteínas de Protozoários/genética , Ativação Transcricional/fisiologia , Animais , Cloranfenicol O-Acetiltransferase/metabolismo , Resistência a Múltiplos Medicamentos/genética , Eletroporação , Entamoeba histolytica/genética , Entamoeba histolytica/crescimento & desenvolvimento , Expressão Gênica/efeitos dos fármacos , Regiões Promotoras Genéticas/efeitos dos fármacos , Regiões Promotoras Genéticas/fisiologia , TransfecçãoRESUMO
Here, we show the relevance of promoter regions (-74 to +24, -167 to -75 and -259 to -168 bp) in the transcriptional activation of the multidrug resistance gene EhPgp1 in Entamoeba histolytica, using mutated plasmids and transfection assays. We also demonstrate that both CCAAT/enhancer binding protein sites (-54 to -43 bp and -198 to -186 bp) are cis-activating elements of gene expression in the drug-resistant (clone C2) and -sensitive (clone A) trophozoites. Nuclear proteins from trophozoites of both clones and C/EBP sequences of the core promoter formed specific complexes, which were abolished by anti-human C/EBPbeta antibodies. UV cross-linking and Western blot assays revealed 25 and 65 kDa bands in urea treated and untreated proteins respectively. The nuclear factors that bind to C/EBP sites were semi-purified by affinity chromatography. They were immunodetected by anti-human C/EBPbeta antibodies and formed a specific complex with the C/EBP probe. The antibodies recognized proteins in the cytoplasm, nucleus and EhkO organelles in immunofluorescence and confocal microscopy experiments. Based on our results, we propose that the C/EBP site at -54 bp stabilizes the transcription pre-initiation complex, whereas the other site at -198 bp may be involved in the formation of a multiprotein complex, which provokes DNA folding and promotes the EhPgp1 gene transcription.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Entamoeba histolytica/genética , Regiões Promotoras Genéticas , Proteínas de Protozoários/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Sítios de Ligação , Resistência a Múltiplos Medicamentos/genética , Resistência a Múltiplos Medicamentos/fisiologia , Regulação da Expressão Gênica , Humanos , Substâncias Macromoleculares , Complexos Multiproteicos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ligação Proteica , Proteínas de Protozoários/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação TranscricionalAssuntos
Antiprotozoários/farmacologia , Resistência a Múltiplos Medicamentos , Entamoeba histolytica/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Animais , Clonagem Molecular , Emetina/farmacologia , Entamoeba histolytica/genética , Amplificação de Genes , Genes MDR , Genes de Protozoários , Fenótipo , Regiões Promotoras Genéticas , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/fisiologia , Transcrição GênicaRESUMO
El desarrollo de mecanismos para evadir la acción de los fármacos y desarrollar resistencia a los mismos es un evento universal en los organismos vivos. Se presenta en virus, bacterias, hongos, plantas y animales. En una población de seres vivos algunos individuos son capaces de encender genes apagados, de mutar la secuencia de otros genes, de sintetizar nuevas moléculas para desarrollar los mecanismos que les permiten sobrevivir y perpetuar la especie en circunstancias adversas. La acumulación de eventos de adaptación y mutagénesis pueden dar lugar a la aparición de organismos con características diferentes a la mayoría de los individuos de su especie, las cuales al acumularse podrían constituir nuevas especies. De manera que los cambios para la adaptación y la sobrevivencia de los individuos constituyen en última instancia las bases de la evolución. Uno de los mecanismos que las células han desarrollado para sobrevivir en presencia de sustancias tóxicas es el llamado fenotipo de resistencia a múltiples drogas o MDR (por sus siglas en inglés, multidrug resistance). Este evento se caracteriza porque las células presentan resistencia a drogas con estructuras químicas y blancos de acción distintos. El fenotipo de MDR se descubrió primeramente en células transformadas de mamífero, las cuales expresan una glicoproteína de aproximadamente 170 kDa en su superficie, denominada Pgp. Posteriormente este mecanismo se ha descubierto en muchas especies, incluyendo a los protozoarios parásitos...
Assuntos
Animais , Entamoeba histolytica , Antiprotozoários , Resistência a Múltiplos Medicamentos , Fenótipo , Regiões Promotoras Genéticas , Clonagem Molecular , Genes de Protozoários , Genes MDR , Emetina , Entamoeba histolytica , Amplificação de Genes , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/fisiologia , Proteínas de Protozoários/genética , Proteínas de Protozoários/fisiologia , Transcrição GênicaRESUMO
Entamoeba histolytica, the protozoan responsible for human amoebiasis, presents the multidrug resistant phenotype due to the expression of the E. histolytica P-glycoproteins EhPgpl and EhPgp5. Here, we studied the protein EhPgp5 encoded by the EhPgp5 gene in emetine-sensitive trophozoites transfected with the pEhNEOPgp5 plasmid carrying the EhPgp5 gene. The transfected trophozoites increased their drug resistance slightly, but became bigger and globular. To investigate other EhPgp5 functions further, we microinjected the EhPgp5 mRNA in Xenopus laevis oocytes. Microinjected oocytes expressed EhPgp5 protein in their membranes and exhibited an ion current not present in the control oocytes. The antisense EhPgp5AS transcript, co-injected with the EhPgp5 mRNA, abolished the exogenous current, showing its specificity. Exogenous current was outward during depolarizing pulses. Reduction of the extracellular Cl- concentration displayed a reversible decrease of the current amplitude. Niflumic acid, 4,4-diisothiocyanatostilbene-2, 2'-disulfonic acid, and other Cl- channel blockers abolished the exogenous current, which was poorly modified by verapamil and changes in osmolarity of the medium. Our results suggest that the EhPgp5 protein could function as a Cl- current inductor and as a coadjuvant factor to avoid drug accumulation in the cell.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/farmacologia , Canais de Cloreto/efeitos dos fármacos , Entamoeba histolytica/genética , Oócitos/metabolismo , Proteínas de Protozoários/farmacologia , Animais , Western Blotting , Clonagem Molecular , Eletrofisiologia , Entamoeba histolytica/química , Microinjeções , Microscopia Confocal , Microscopia de Fluorescência , Técnicas de Patch-Clamp , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Xenopus laevisRESUMO
We have studied the cellular location and the efflux pump function of the Entamoeba histolytica P-glycoproteins (EhPgps) in drug-sensitive and -resistant trophozoites. Polyclonal antibodies against the EhPgp384 polypeptide (375-759 amino acids) revealed a 147-kDa protein by Western blot. The band intensity correlated with the emetine-resistance of the trophozoites. Through the confocal microscope, using the anti-EhPgp384 and fluorescein secondary antibodies, the EhPgps were found in a complex vesicular network, in the plasma membrane and outside of the cells. Transmission electron microscopy assays confirmed that drug-resistant trophozoites presented four to five times more EhPgps than sensitive cells. Fluorescence co-localization experiments using rhodamine-123 (R123) and the anti-EhPgp384 antibodies suggested the interaction between EhPgps and the drug. R123 efflux kinetics evidenced that the emetine-resistant trophozoites displayed a drug efflux kinetic four times higher than the drug-sensitive trophozoites, which was reduced by verapamil in both cases. EhPgps may participate in avoiding drug accumulation in the trophozoites by two putative mechanisms: (1) the direct extrusion of the drug from the plasma membrane, and (2) an indirect transport mechanism in which the drug is trapped by EhPgps and concentrated within vesicles that drive the drug to the plasma membrane.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/fisiologia , Antiprotozoários/farmacologia , Entamoeba histolytica/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/imunologia , Sequência de Aminoácidos , Animais , Antígenos de Protozoários/imunologia , Western Blotting , Bloqueadores dos Canais de Cálcio/farmacologia , Resistência a Múltiplos Medicamentos , Entamoeba histolytica/imunologia , Entamoeba histolytica/ultraestrutura , Imunoquímica , Cinética , Microscopia Confocal , Microscopia Eletrônica , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção , Verapamil/farmacologiaRESUMO
Entamoeba histolytica presents the evolutionarily conserved multidrug-resistance (MDR) phenotype, discovered in mammalian cells. MDR cells overexpress the membrane P-glycoprotein, which excludes unrelated drugs from the cytoplasm. E. histolytica mutants exhibit cross-resistance to unrelated drugs, which are pumped out from the cytoplasm. In drug-resistant trophozoites, the constitutively expressed EhPg1 gene appears to be up-regulated by a C/EBP-like factor and a multiprotein complex that were not found in drug-sensitive trophozoites. The drug-induced EhPgp5 gene, on the other hand, appears to be up-regulated by AP-1 and HOX factors. Here we review the main physiological and molecular facts of the MDR phenotype in E. histolytica. Copyright 1999 Harcourt Publishers Ltd.