Correlación entre pruebas y escalas de valoración funcional en el seguimiento a la adaptación protésica de personas con amputación de miembro inferior / Correlation among tests and functional assessment scales in the follow-up of prosthetic adaptation in people with lower limb amputation

Introducción: Existe gran disponibilidad de pruebas funcionales y escalas para evaluar distintos aspectos en la adaptación de personas amputadas, pero aún no hay consenso respecto a las más apropiadas. Objetivos: Describir las medidas de correlación y asociación entre tres pruebas funcionales para amputados de miembros inferiores y definir cuál es la más adecuada. Evaluar la satisfacción general de los usuarios de prótesis de miembro inferior y su asociación con las pruebas funcionales. Métodos: Se incluyeron 83 personas con amputación unilateral de miembro inferior, usuarios de prótesis exomodulares de bajo costo. Instrumentos: escala de Houghton, la subescala de movilidad del cuestionario de evaluación protésica y la prueba de marcha de 2 minutos (2MWT). El análisis estadístico se realizó mediante la prueba chi cuadrado y el coeficiente de correlación de Spearman. Resultados: Las pruebas funcionales tuvieron una correlación y asociación aceptable entre sí, la correlación entre la escala de Houghton y el 2MWT fue de mayor magnitud (r=0,56 para la muestra total; r=0,53 para amputados debajo de rodilla). Las medidas de asociación no lograron resultados estadísticamente significativos para amputados por encima de la rodilla, ni para la satisfacción general. Conclusiones: La escala de Houghton y el 2MWT mostraron una buena correlación y asociación entre sí por lo que pueden ser considerados como instrumentos de primera línea para el seguimiento de los usuarios de prótesis exomodulares de miembro inferior. Para la satisfacción general no se identificó asociación importante con los instrumentos evaluados.(AU)

Introduction: There is a wide variety of functional tests and scales for the assessment of different aspects in the adaptation of amputees, but there is still no consensus on which are the most appropriate. Objectives: To describe the measures of correlation and association among three functional tests for lower-limb amputees and to define the most appropriate for this assessment. To assess general satisfaction in lower-limb prostheses users and its association with the functional tests. Methods: We included 83 unilateral lower-limb amputees who were users of low-cost exoskeletal prostheses. The instruments employed were the Houghton scale, the Prosthesis Evaluation Questionnaire - Mobility Scale (PEQ-MS) and the 2-minute walk test (2MWT). The statistical analysis was performed using the chi-square test and Spearman's correlation coefficient. Results: The functional tests evaluated had an acceptable correlation and association with each other, but the Spearman correlation between the Houghton scale and the 2MWT was of greater significance (whole sample: r=0.56; below-knee amputees: r=0.53). The association measures did not achieve statistically significant results for above-knee amputees or for general satisfaction. Conclusions: The Houghton Scale and the 2MWT showed a good correlation and association with each other, becoming possible first-line instruments for the follow-up of exoskeletal lower limb prosthesis users. No significant association was identified between satisfaction and the instruments measured.(AU)

[Correlation among tests and functional assessment scales in the follow-up of prosthetic adaptation in people with lower limb amputation]. / Correlación entre pruebas y escalas de valoración funcional en el seguimiento a la adaptación protésica de personas con amputación de miembro inferior.

INTRODUCTION: There is a wide variety of functional tests and scales for the assessment of different aspects in the adaptation of amputees, but there is still no consensus on which are the most appropriate. OBJECTIVES: To describe the measures of correlation and association among three functional tests for lower-limb amputees and to define the most appropriate for this assessment. To assess general satisfaction in lower-limb prostheses users and its association with the functional tests. METHODS: We included 83 unilateral lower-limb amputees who were users of low-cost exoskeletal prostheses. The instruments employed were the Houghton scale, the Prosthesis Evaluation Questionnaire - Mobility Scale (PEQ-MS) and the 2-minute walk test (2MWT). The statistical analysis was performed using the chi-square test and Spearman's correlation coefficient. RESULTS: The functional tests evaluated had an acceptable correlation and association with each other, but the Spearman correlation between the Houghton scale and the 2MWT was of greater significance (whole sample: r=0.56; below-knee amputees: r=0.53). The association measures did not achieve statistically significant results for above-knee amputees or for general satisfaction. CONCLUSIONS: The Houghton Scale and the 2MWT showed a good correlation and association with each other, becoming possible first-line instruments for the follow-up of exoskeletal lower limb prosthesis users. No significant association was identified between satisfaction and the instruments measured.

Mental health, migration stressors and suicidal ideation among Latino immigrants in Spain and the United States.

BACKGROUND: Immigration stress appears to augment the risk for suicide behaviors for Latinos. Yet, specific risk factors that contribute to suicidal ideation (SI) among diverse Latino immigrant populations are not well established. METHODS: Data were collected in Boston, Madrid and Barcelona using a screening battery assessing mental health, substance abuse risk, trauma exposure, demographics, and sociocultural factors. Prevalence rates of lifetime and 30-day SI were compared across sites. Logistic regression modeling was used to identify sociodemographic, clinical, and sociocultural-contextual factors associated with 30-day SI. RESULTS: Five hundred and sixty-seven Latino patients from primary care, behavioral health and HIV clinics and community agencies participated. Rates of lifetime SI ranged from 29-35%; rates for 30-day SI were 21-23%. Rates of SI were not statistically different between sites. Factors associated with SI included exposure to discrimination, lower ethnic identity, elevated family conflict, and low sense of belonging (P<0.01). In the adjusted model, higher scores on depression, posttraumatic stress disorder, and trauma exposure were significantly associated with 30-day SI (OR=1.14, 1.04, and 7.76, respectively). Greater number of years living in the host country was significantly associated with increased odds of having SI (OR=2.22) while having citizenship status was associated with lower odds (OR=0.45). CONCLUSION: Latinos suffering depression, trauma exposure, and immigration stressors are more likely to experience SI. Despite differences in country of origin, education, and other demographic factors between countries, rates of SI did not differ. Recommendations for prevention and clinical practice for addressing suicidal ideation risk among Latino immigrants are discussed.

Analysis of Olig2 and YKL-40 expression: a clinicopathological/immunohistochemical study for the distinction between subventricular zone II and III glioblastomas.

Glioblastomas (GBs) are the most common and lethal primary brain tumors in the adults. Glioblastomas originates either from astrocytes that have accumulated mutations and de-differentiated or from neural stem cells within the subventricular zone (SVZ) in close contact with the vasculature. Recently, several studies have hypothesized that gliomagenesis occurs in perivascular niches with highly invasive peripheral proliferating zones. The purpose of our study was to investigate the pathological and clinical significance of Olig2 and YKL40 immunoexpression in 152 GBs in relationship to the SVZ II and III. Olig2 expressions were successfully detected in 12 (15.58%) of 77 SVZ type II GBs and 16 (21.3%) of 75 SVZ type III GBs, respectively. YKL-40 expression was observed in 45 (58.4%) of 77 SVZ type II GBs and in 17 (22.6%) of 75 SVZ type III GBs, respectively. Stepwise multivariate Cox proportional hazards models were used, and the prognostic factors to significantly impact OS were: PFS < 54 weeks (HR: 5.86; CI: 3.02-11.33; p = 0.00); radiotherapy (HR: 0.34; CI: 0.18-0.60; p = 0.00); radio- and chemotherapy (HR: 0.05; CI: 0.03-0.10; p = 0.0), and YKL-40+ GBs (HR: 1.61; CI: 1.28-2.31; p = 0.01).

STAT3 inhibition reduces toxicity of oncolytic VSV and provides a potentially synergistic combination therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a refractory malignancy with a high mortality and increasing worldwide incidence rates, including the United States and central Europe. In this study, we demonstrate that a specific inhibitor of signal transducer and activator of transcription 3 (STAT3), NSC74859, efficiently reduces HCC cell proliferation and can be successfully combined with oncolytic virotherapy using vesicular stomatitis virus (VSV). The potential benefits of this combination treatment are strengthened by the ability of NSC74859 to protect primary hepatocytes and nervous system cells against virus-induced cytotoxicity, with an elevation of the VSV maximum tolerated dose in mice. Hereby we propose a strategy for improving the current regimen for HCC treatment and seek to further explore the molecular mechanisms underlying selective oncolytic specificity of VSV.

Gammapatías biclonales: estudio retrospectivo de 47 pacientes / Biclonal gammopathies: retrospective study of 47 patients

Objetivo. Las gammapatías biclonales se caracterizan por una proliferación clonal de cálulas plasmáticas, o sus progenitores linfoides B, con producción de dos inmunoglobulinas anormales (proteínas M o paraproteínas). No conocemos estudios que hayan analizado esta patología en España. Hemos estudiado las enfermedades subyacentes, características de las paraproteínas y evolución de una serie de pacientes con gammapatía biclonal. Material y métodos. Se revisaron las gammapatías clonales del Servicio de Inmunología del Hospital Puerta de Hierro de Madrid, entre los años 1970 y 2011, seleccionando aquellos pacientes con gammapatía biclonal en una determinación. Se recogieron datos epidemiológicos, enfermedad de base, patologías asociadas, terapias recibidas, paraproteína y cuantificación de inmunoglobulinas. Resultados. De los 1.626 casos de gammapatías clonales, 47 eran gammapatía biclonal (2,89%). La mediana de seguimiento fue de 2 años. La principal entidad asociada fue la gammapatía biclonal de significado indeterminado. La composición de paraproteínas más frecuente fue IgG-IgG. En el 81% de los pacientes con una segunda determinación de paraproteína, había desaparecido al menos un componente M. Un tercio de los pacientes no había recibido tratamiento. Conclusiones. Las gammapatías biclonales se asocian fundamentalmente a gammapatía biclonal de significado indeterminado. Ninguna gammapatía biclonal de significado indeterminado evolucionó a patología maligna. En un elevado porcentaje desapareció al menos uno de los dos componentes clonales, a veces de forma espontánea (AU)

Objectives. Biclonal gammopathies are characterized by the clonal proliferation of plasma cells or their B-lymphoid progenitors and are associated with the production of abnormal immunoglobulins (M proteins or paraproteins). There are no known studies that have analyzed this disease in Spain. We studied the underlying diseases, characteristics of paraproteins and the evolution of a series of patients with biclonal gammopathy. Material and methods. We reviewed clonal gammopathies at the Department of Immunology of Hospital Puerta de Hierro in Madrid, between 1970 and 2011, selecting those patients with biclonal gammopathy in one reading. We collected data on the patient's epidemiology, underlying disease, associated diseases, therapies and paraprotein and immunoglobulin levels. Results. Of the 1626 cases of clonal gammapathies, 47 were biclonal gammopathy (2.89%). The median follow-up was 2 years. The main associated condition was biclonal gammopathies of undetermined significance (BGUS). The most common paraprotein combination was IgG-IgG. Upon conducting a second paraprotein reading, 81% of the patients had lost at least 1 monoclonal component. A third of the patients had not undergone treatment. Conclusions. Biclonal gammopathy are fundamentally associated with biclonal gammopathies of undetermined significance. No biclonal gammopathies of undetermined significance evolved to a malignant disease. In a high percentage of patients, at least 1 of the 2 clonal components disappeared, sometimes spontaneously (AU)

Biclonal gammopathies: Retrospective study of 47 patients. / Gammapatías biclonales: estudio retrospectivo de 47 pacientes.

OBJECTIVES: Biclonal gammopathies are characterized by the clonal proliferation of plasma cells or their B-lymphoid progenitors and are associated with the production of abnormal immunoglobulins (M proteins or paraproteins). There are no known studies that have analyzed this disease in Spain. We studied the underlying diseases, characteristics of paraproteins and the evolution of a series of patients with biclonal gammopathy. MATERIAL AND METHODS: We reviewed clonal gammopathies at the Department of Immunology of Hospital Puerta de Hierro in Madrid, between 1970 and 2011, selecting those patients with biclonal gammopathy in one reading. We collected data on the patient's epidemiology, underlying disease, associated diseases, therapies and paraprotein and immunoglobulin levels. RESULTS: Of the 1626 cases of clonal gammapathies, 47 were biclonal gammopathy (2.89%). The median follow-up was 2 years. The main associated condition was biclonal gammopathies of undetermined significance (BGUS). The most common paraprotein combination was IgG-IgG. Upon conducting a second paraprotein reading, 81% of the patients had lost at least 1 monoclonal component. A third of the patients had not undergone treatment. CONCLUSIONS: Biclonal gammopathy are fundamentally associated with biclonal gammopathies of undetermined significance. No biclonal gammopathies of undetermined significance evolved to a malignant disease. In a high percentage of patients, at least 1 of the 2 clonal components disappeared, sometimes spontaneously.

Serum IL-12 is increased in Mexican obese subjects and associated with low-grade inflammation and obesity-related parameters.

Interleukin-(IL-) 12 has been recently suggested to participate during development of insulin resistance in obese mice. Nevertheless, serum IL-12 levels have not been accurately determined in overweight and obese humans. We thus studied serum concentrations of IL-12 in Mexican adult individuals, examining their relationship with low-grade inflammation and obesity-related parameters. A total of 147 healthy individuals, 43 normal weight, 61 overweight, and 43 obese subjects participated in the study. Circulating levels of IL-12, tumor necrosis factor-alpha (TNF- α ), leptin, insulin, glucose, total cholesterol, and triglyceride were measured after overnight fasting in all of the study subjects. Waist circumference and body fat percentage were recorded for all the participants. Serum IL-12 was significantly higher in overweight and obese individuals than in normal weight controls. Besides being strongly related with body mass index (r = 0.5154), serum IL-12 exhibited a significant relationship with abdominal obesity (r = 0.4481), body fat percentage (r = 0.5625), serum glucose (r = 0.3158), triglyceride (r = 0.3714), and TNF- α (r = 0.4717). Thus, serum levels of IL-12 are increased in overweight and obese individuals and show a strong relationship with markers of low-grade inflammation and obesity in the Mexican adult population. Further research is needed to understand the role of IL-12 in developing obesity-associated alterations in humans.

Large deletions and splicing-site mutations in the STK11 gene in Peutz-Jeghers Chilean families.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder characterized by mucocutaneous melanocytic macules, gastrointestinal hamartomatous polyposis and an increased risk of various neoplasms. Germline mutations in the serine/threonine kinase 11 (STK11) gene have been identified as a cause for PJS. The aim of this study was to characterize the genotype of Chilean PJS patients. Mutation screening of 13 patients from eight PJS families was performed using a single strand conformation polymorphism analysis, DNA sequencing and multiplex ligation-dependent probe amplification assay. The breakpoints of the genomic rearrangements were assessed by a long-range polymerase chain reaction and sequencing. The results revealed the existence of seven different pathogenic mutations in STK11 gene in seven unrelated families, including three point mutations and four large genomic deletions. Three of these point mutations (43%, 3/7) may be considered as novel. Our results showed that a germline mutation is present in STK11 in 88% of probands fulfilling the diagnostic criteria of PJS. In this study, the combination of two different experimental approaches in the screening of the STK11 in PJS, led to a higher percentage of mutation detection.

¿Es la vacunación antigripal el nuevo Belerofonte? Sobre la vacunación antigripal en Atención Primaria / Is influenza vaccination the new Bellerophon? The flu vaccine in Primary Care

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Notch signalling regulates cytokine production by CD8+ and CD4+ T cells.

The Notch signalling pathway regulates several aspects of cellular differentiation such as T lineage commitment and effector functions on peripheral T cells; however, there is limited information regarding Notch receptor expression on different T cell subsets and the putative role of the different receptors on T cell effector function. Here, we studied the protein expression of Notch receptors on murine T cells in vitro and in vivo and analysed the role of the Notch pathway in cytokine production by CD4+ and CD8+ T cells. We found that resting CD4+ and CD8+ T cells do not express Notch receptors, but they upregulate Notch 1 and Notch 2 shortly after in vitro and in vivo activation. Using a γ-secretase inhibitor, which blocks Notch signalling through all Notch receptors, we demonstrated that the Notch pathway regulates IL-10 production by CD4+ T cells and IFN-γ and IL-17 production by CD8+ T cells. These results suggest that Notch 1 and 2 are expressed by CD4+ and CD8+ T cells and represent the putative Notch receptors that regulate effector functions and cytokine production by these cells.

High yield synthesis, purification and characterisation of the RNase L activators 5'-triphosphate 2'-5'-oligoadenylates.

Upon viral infection, double-stranded viral RNA is detected very early in the host cell by several cellular 2'-5' oligoadenylate synthetases, which synthesize 2'-5' adenylate oligonucleotides that activate the cellular RNase L, firing an early primary antiviral response through self and non-self RNA cleavage. Transfecting cells with synthetic 2'-5' adenylate oligonucleotides activate RNase L, and thus provide a useful shortcut to study the early steps of cellular and viral commitments into this pathway. Defined 2'-5' adenylate oligonucleotides can be produced in vitro, but their controlled synthesis, purification, and characterisation have not been reported in detail. Here, we report a method suitable to produce large amounts of 2-5As of defined lengths in vitro using porcine OAS1 (pOAS) and human OAS2 (hOAS). We have synthesized a broad spectrum of 2-5As at the milligram scale and report an HPLC-purification and characterisation protocol with quantified yield for 2-5A of various lengths.

Detection of Helicobacter and Campylobacter spp. from the aquatic environment of marine mammals.

The mechanism by which Helicobacter species are transmitted remains unclear. To examine the possible role of environmental transmission in marine mammals, we sought the presence of Helicobacter spp. and non-Helicobacter bacteria within the order Campylobacterales in water from the aquatic environment of marine mammals, and in fish otoliths regurgitated by dolphins. Water was collected from six pools, two inhabited by dolphins and four inhabited by seals. Regurgitated otoliths were collected from the bottom of dolphins' pools. Samples were evaluated by culture, PCR and DNA sequence analysis. Sequences from dolphins' water and from regurgitated otoliths clustered with 99.8-100% homology with sequences from gastric fluids, dental plaque and saliva from dolphins living in those pools, and with 99.5% homology with H. cetorum. Sequences from seals' water clustered with 99.5% homology with a sequence amplified from a Northern sea lion (AY203900). Control PCR on source water for the pools and from otoliths dissected from feeder fish were negative. The findings of Helicobacter spp. DNA in the aquatic environment suggests that contaminated water from regurgitated fish otoliths and perhaps other tissues may play a role in Helicobacter transmission among marine mammals.

Acyclic phosphonate nucleotides and human adenylate kinases: impact of a borano group on alpha-P position.

Adenylate kinases are involved in the activation of antiviral drugs such as the acyclic phosphonates analogs PMEA and (R)PMPA. We examine the in vitro phosphorylation of PMEA and PMPA bearing a borano- or a H- group on the phosphorus atom. The alpha-borano or alpha-H on PMEA and PMPA were detrimental to the activity of recombinant human AMP kinases 1 and 2. Docking PMEA to the active site of AMP kinase 1 indicated that the borano group may prevent two conserved critical Arg interactions with the alpha-phosphate, resulting in substrate bad positioning.

Hernia hiatal gigante: reporte de un caso / Giant hiatal hernia: a case report

La hernia de hiato es una situación patológica que se da cuando parte del estómago se introduce hacia el tórax. El esófago entra en el abdomen desde el tórax a través de un agujero o hiato que se encuentra en el diafragma. El estómago protruye a través de este hiato debilitado y produce ardores (pirosis) y dolor torácico. La persistencia en el tiempo de esta hernia, puede provocar una metaplasia de la mucosa esofágica dando al lugar al esófago de Barret el cual puede malignizar produciéndose cáncer de esófago. (1) La hernia de hiato es relativamente frecuente, afectando hasta un 20 por ciento de la población. Del total de pacientes con el trastorno, cerca del 10 por ciento son asintomáticos, dependiendo del grado de protrución estomacal y de que tanto esté afectado el esfinter esofágico inferior (EEI). Un 40 por ciento de las hernias de hiato son hernias deslizantes, en las que el EEI protruye conjuntamente con una porción del estómago y solo un 5 por ciento son paraesofágicas, en la que solo una porción del estómago se hace intratorácica mientras tanto que el EEI permanece intraabdominal. Los síntomas más comunes de una hernia de hiato incluyen pirosis, dolor torácico, disfagia, palpitaciones y ocasionalmente regurgitación o reflujo gastroesofágico. El diagnóstico de una hernia hiatal comienza con el éxamen físico por razón de la sintomatología. Los estudios radiográficos y la endoscopia digestiva demuestran la hernia hiatal y ayudan a descartar otras causas de molestias digestivas altas. (2) Se recomienda un procedimiento quirúrgico conocida como fundoplicación de Nissen, (3) Cuando los síntomas causados por una hernia de hiato son tan severas que pueden resultar en lesiones al esófago o incluso cáncer del esófago. (6) Se trata de lactante mayor de seis meses de edad quien es natural de la localidad y procedente de Cordero, quien inicia enfermedad actual el día de hoy en la madrugada según refiere la madre, caracterizado por vómitos en número incontables.

Cierre diferido en onfalocele no roto: reporte de un caso / Close deferred not broken in omphalocele: a case report

El término onfalocele fue definido por Benson en 1949 y se atribuye a Paré su descripción inicial en la primera mitad del siglo XVI. Se trata de una herniación de las vísceras abdominales que están cubiertas por un saco formado por peritoneo, membrana amniótica y gelatina de Warthon y que se continúa con el cordón umbilical. (1) Esta herniación es consecuencia de una alteración en la formación de la pared abdominal anterior del embrión. El defecto se sitúa soempre en la región umbilical y puede ser de tamaño variable, considerándose un onfalocele gigante cuando el defecto supera los 10 cm. Generalmente contiene asas de intestino delgado, y en los de mayor tamaño, el hígado. (2) La presencia de otras malformaciones asociadas no es rara y puede condicionar el pronóstico del recién nacido. El 25 por ciento presentan una cardiopatía congénita, siendo más frecuente la tetralogía de Fallot. La frecuencia de esta entidad varía de unas regiones a otras y oscila entre 1/6.000 hasta 1/60.000 de los recién nacidos vivos, incluyendo los casos de gastrosquitis. Puede diagnosticarse mediante las ecografías prenatales a partir del cuarto mes, y en un futuro serán subsidiarias de corregirse mediante cirugía fetal. (3) Existe controversia en relación a la necesidad de una cesárea programada para el nacimiento. La cesárea previene la lesión de las vísceras herniadas, pero el parto vaginal logra una mayor madurez del feto. En general los niños afectados de onfaloceles grandes deben nacer mediante cesárea electiva, pero los que presentan onfaloceles pequeños pueden nacer mediante parto vaginal. Con independencia de la decisión adoptada es importante que los neonatólogos y cirujanos pediátricos estén alertados del nacimiento para realizar una adecuada valoración del recién nacido lo antes posible. El tratamiento tiene por misión reintroducir las vísceras en la cavidad abdominal restaurando la integridad de la misma antes de que se produzca la contaminación del contenido herniario.

High-yield production of short GpppA- and 7MeGpppA-capped RNAs and HPLC-monitoring of methyltransfer reactions at the guanine-N7 and adenosine-2'O positions.

Many eukaryotic and viral mRNAs, in which the first transcribed nucleotide is an adenosine, are decorated with a cap-1 structure, (7Me)G5'-ppp5'-A(2'OMe). The positive-sense RNA genomes of flaviviruses (Dengue, West Nile virus) for example show strict conservation of the adenosine. We set out to produce GpppA- and (7Me)GpppA-capped RNA oligonucleotides for non-radioactive mRNA cap methyltransferase assays and, in perspective, for studies of enzyme specificity in relation to substrate length as well as for co-crystallization studies. This study reports the use of a bacteriophage T7 DNA primase fragment to synthesize GpppAC(n) and (7Me)GpppAC(n) (1 < or = n < or = 9) in a one-step enzymatic reaction, followed by direct on-line cleaning HPLC purification. Optimization studies show that yields could be modulated by DNA template, enzyme and substrate concentration adjustments and longer reaction times. Large-scale synthesis rendered pure (in average 99%) products (1 < or = n < or = 7) in quantities of up to 100 nmol starting from 200 nmol cap analog. The capped RNA oligonucleotides were efficient substrates of Dengue virus (nucleoside-2'-O-)-methyltransferase, and human (guanine-N7)-methyltransferase. Methyltransfer reactions were monitored by a non-radioactive, quantitative HPLC assay. Additionally, the produced capped RNAs may serve in biochemical, inhibition and structural studies involving a variety of eukaryotic and viral methyltransferases and guanylyltransferases.

[Dengue virus: viral targets and antiviral drugs]. / Le virus de la dengue : cibles virales et antiviraux.

This work reviews the opportunities and scientific bases in the development of anti-dengue drugs. The timeliness of anti-dengue drug development is addressed in the context of the growing impact of dengueworldwide and existing strategies to fight the virus. The antiviral approach in therapy or prophylaxis during an epidemic as well as the impact of recent technological advances in drug-discovery and antiviral chemotherapy on the development of anti-dengue drugs are discussed. An analysis of current sources of synthetic or natural drugs is provided. Finally, we summarize the current knowledge on dengue virus proteins, which are currently considered the most viable as drug targets, as the envelop protein E and non-structural proteins NS3 and NS5 carrying protease, helicase, RNA triphosphatase, methyltransferase and RNA-dependent RNA polymerase activities. Other viral proteins proposed to be part of the replication complex and the complex itself are considered as potential targets of anti-dengue drugs. State-of-the-art methods are listed, that are expected to allow the discovery, design, and characterisation of anti-dengue drugs effective against the four serotypes.