Deep brain stimulation in Latin America in comparison with the US and Europe in a real-world population: indications, demographics, techniques, technology, and adverse events.

OBJECTIVE: The aim of this study was to provide geographic comparisons of deep brain stimulation (DBS) procedures in Latin America with the US and Europe regarding primary indications, demographic information, clinical and device-related adverse events, technology used, and patient outcomes using the Medtronic Product Surveillance Registry data as of July 31, 2021. METHODS: Two thousand nine hundred twelve patients were enrolled in the registry (2782 received DBS and 1580 are currently active). Fourteen countries contributed 44,100 years of device experience to the registry. DBS centers in Latin America are located in Colombia (n = 3), Argentina (n = 1), Brazil (n = 1), and Mexico (n = 1). Fisher's exact test was used to compare the difference in proportions of categorical variables between regions. The Wilcoxon signed-rank test was used for the EQ-5D index score change from baseline to follow-up. RESULTS: The most common indication for DBS was Parkinson's disease across all regions. In Latin America, dystonia was the second most common indication, compared to essential tremor in other regions. There was a striking finding with respect to age-patients were an average of 10 years younger at DBS implantation in Latin America. This difference was most likely due to the greater number of patients with dystonia receiving the device implants. The intraoperative techniques were quite similar, showing the same level of quality and covering the main principles of the surgeries with some variations in the brand of frames, planning software, and microrecording systems. Rechargeable batteries were significantly more common in Latin America (72.37%) than in the US (6.44%) and Europe (9.9%). Staging of the DBS procedure differed, with only 11.84% in Latin America staging the procedure compared with 97.58% and 34.86% in the US and Europe, respectively. The EQ-5D score showed significant improvements in all regions during the first 6-12 months (p < 0.0001). However, the 24-month follow-up only showed an improvement in the scale for Latin America (p < 0.0001). CONCLUSIONS: DBS was performed in Latin America with similar indications, techniques, and technology as in the US and Europe. Important differences were found, with Latin America implementing more regular use of rechargeable devices, including younger patients at the time of surgery, and showing more sustained quality of life improvements at 24 months of follow-up. The authors hypothesize that these disparities stem from differences in resources among regions. However, more studies are needed to standardize DBS practice across the world to improve patients' quality of life and provide high-quality care.

Medicamentos bioterapéuticos: uso de toxinas botulínicas en la era de biosimilares / Biotherapeutic medicines: use of botulinum toxins in the era of biosimilars

Introducción: Las toxinas botulínicas son medicamentos bioterapéuticos con grandes aplicaciones en el campo de la neurología, como la cefalea y los movimientos anormales. Debido a la importancia médica y al incremento de las indicaciones terapéuticas de la toxina botulínica, este artículo pretende hacer claridad acerca de la terminología básica con respecto a la naturaleza de este medicamento, a las diferencias estructurales con medicamentos convencionales y aspectos importantes en relación con su potencia biológica e inmunogenicidad, para así comprender las potenciales diferencias entre las toxinas disponibles y conceptuar en torno a la no intercambiabilidad o sustitución de una toxina por otra. Materiales y métodos: Revisión no sistemática, según lo recomendado en la Escala para la Verificación de los Artículos Revisiones Narrativas (Sanra). Conclusiones: Los medicamentos biológicos no son intercambiables entre sí, aunque demuestren bioequivalencia. No se pueden evaluar como medicamentos genéricos intercambiables porque son biológicos; no existen estudios comparativos cabeza a cabeza; son diferentes, debido al proceso individual de manufactura.

Introduction: Botulinum toxins are biotherapeutic drugs with great applications in the field of neurology such as headache and abnormal movements. Due to the medical importance and the increase in therapeutic indications of botulinum toxin, this article aims to clarify the basic terminology regarding the nature of this drug, the structural differences with conventional drugs and important aspects in relation to its biological potency and immunogenicity in order to understand the potential differences between the available toxins and conceptualize regarding the non-interchangeability or substitution of one toxin for another. Materials and methods: Non-systematic review as recommended in the Scale for the Verification of Narrative Review Articles (SANRA). Conclusions: Biological drugs are not interchangeable with each other, even if they demonstrate bioequi-valence. They cannot be evaluated as interchangeable generic drugs because they are biologics. There are no head-to-head comparative studies. They are different due to the individual manufacturing process.

Consenso de la Asociación Colombiana de Neurología sobre el uso de apomorfina en la enfermedad de Parkinson / Colombian Association of Neurology Consensus on the use of Apomorphine in Parkinson's disease

La apomorfina es un agonista dopa que se viene usando desde hace más 25 años en el tratamiento de la enfermedad de Parkinson avanzada con complicaciones motoras complejas, por lo cual sigue siendo de gran importancia en el tratamiento de esta etapa de la enfermedad. En el siguiente escrito, realizado por el Comité de Movimientos Anormales de la Asociación Colombiana de Neurología, se hace una revisión respecto a la medicación, su eficacia y el papel en el manejo de la enfermedad de Parkinson, así como una comparación entre las diferentes terapias avanzadas disponibles hoy en día. De la misma manera el Comité hace recomendaciones sobre las indicaciones, elección de candidatos y protocolos para el inicio de las diferentes formas de administración (intermitente e infusión continua) para optimizar el uso de esta terapia y facilitar la adherencia al tratamiento. Por otra parte, se revisan los efectos adversos relacionados con la terapia y se hacen recomendaciones sobre el manejo de las mismas, el seguimiento que se debe hacer a los pacientes que reciban apomorfina y las claves en el tratamiento a largo plazo. long term.

Apomorphine is a dopamine agonist that has been used for more than 25 years in the treatment of advanced Parkinson's disease with complex motor complications, becoming an important treatment option for this stage of the disease. In the following document, written by the movement disorders committee of the Colombian Association of Neurology, an extensive review is made about this medication, its efficacy and role in the management of Parkinson's disease as well as a comparison between the different advanced therapies available today. Additionally, recommendations about the indications, election of candidates and protocols for choosing between the different forms of administration (intermittent and continuous infusion) are establish according current evidence in order to help clinicians to optimize the use of this therapy and facilitate adherence to treatment. On the other hand, adverse effects related to the therapy are reviewed and recommendations are made about their management, as well as a protocol to follow-up patients receiving apomorphine and keys in the long term.

Genética de las distonías / Genetic classification of dystonia

RESUMEN Con el avance de la secuenciación genética y otras técnicas se ha logrado avanzar de manera significativa en la detección de formas monogénicas de la distonía así como en la contribución de varios factores genéticos en la génesis de esta condición.

SUMMARY With the refinement of genetic sequencing and many other techniques, monogenic forms of dystonia as well as various genetic contributions and epigenetic factors are now available to guide the clinician in the pursue of an accurate diagnosis of this condition.

Genética de las distonías / Genetic classification of dystonia

Con el avance de la secuenciación genética y otras técnicas se ha logrado avanzar de manera significativa en la detección de formas monogénicas de la distonía así como en la contribución de varios factores genéticos en la génesis de esta condición.

SUMMARY With the refinement of genetic sequencing and many other techniques, monogenic forms of dystonia as well as various genetic contributions and epigenetic factors are now available to guide the clinician in the pursue of an accurate diagnosis of this condition.

Deep brain stimulation of the globus pallidus internus or ventralis intermedius nucleus of thalamus for Holmes tremor.

Holmes tremor (HT) is a difficult-to-treat, very disabling symptomatic condition which characteristically appears weeks to years after a brain lesion. It features a unique combination of rest, action, and postural tremors. Pharmacotherapy is mostly not effective. Chronic deep brain stimulation (DBS) of ventralis intermedius nucleus (Vim) of thalamus has been described as being the best surgical approach in singular case series; various authors observe, however, cases with partial responses only; therefore, alternatives are still needed. We report ten patients with HT unresponsive to best medical therapy who underwent DBS in our center from March 2002 to June 2012. Based in our previous experience dealing with cases of unsatisfactory Vim intraoperative tremor control and in order to optimize surgical results, presurgical target planning included two Nuclei: Vim and posteroventral Globus pallidus internus (GPi) (Espinoza et al. 2010; Espinoza et al. Stereotact Funct Neurosurg 90(suppl 1):1-202, p 61, 2012). Definitive chosen target was decided after single-cell microelectrode recording, intraoperative test stimulation, thresholds for stimulation-induced adverse effects and best clinical response compared to baseline status. Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) was used to evaluate outcome. The electrode was implanted in the nucleus with the best tremor suppression achievement; on the other hand, GPi DBS was initially decided if one of the following conditions was present: (a) If Vim nucleus anatomy was grossly altered; (b) when intraoperative tremor control was unsatisfactory despite Vim high-intensity stimulation; or (c) if unaffordable side effects or even tremor worsening occurred during intraoperative macrostimulation. Seven patients received definitive Gpi DBS implantation, while three patients received Vim DBS. In all observed cases, we observed an improvement on the TRS. In two cases where Vim thalamic anatomy was altered by the pathological insult GPI was planned from the beginning, and same was true in two additional cases where the Gpi nucleus showed major alterations allowing only Vim planning. Over all cases, the average improvement in tremor was of 2.55 points on the TRS or a 64 % increase in measured results; with a minimum of 1 point (25 %) improvement in one case and a maximum of 4 points (100 % improvement) also in one case. All the results were sustained at 2 years follow-up. One case with predominant resting component, implanted in the GPi, achieved the maximum possible tremor reduction (from 4 to 0 points, meaning 100 % tremor reduction); in the nine resting cases, the average reduction was of 3 points (or 75 %). DBS demonstrated in this case series adequate tremor control in 10 patients unresponsive to medical therapy. Presurgical planning of two targets allowed choosing best optimal response. Gpi stimulation could be considered as an alternative target for cases in which thalamic anatomy is considerably altered or Vim intraoperative stimulation does not produce satisfactory results.

Neurosurgical treatment for dystonia: long-term outcome in a case series of 80 patients.

INTRODUCTION: In this study, we assessed the outcomes of patients with dystonia who underwent surgery treatment following the same algorithm. PATIENTS AND METHODS: Eighty consecutive patients with dystonia were submitted to neurosurgical management by means of intrathecal pump implantation, pallidotomy or deep brain stimulation (GPi or VIM). These patients included 48 patients with primary dystonia and 32 patients with secondary dystonia. Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to access pre- and post-operative outcomes. Patients were followed from 12 to 114 months. RESULTS: Mean improvement in BFMDRS score among patients with PrD was 87.54% and 42.21% for SeD. Hemidystonic patients in both groups (PrD, SeD) showed a mean improvement in BFMDRS of 71.05% with GPiDBS. Patients with SeD due to previous perinatal insults showed a mean improvement in BFMDRS of 41.9%, with better results in purely dyskinetic patients (mean improvement of 61.2%). CONCLUSION: Use of the proposed algorithm facilitated surgical decision planning, which translated in improved diagnostic rates, earlier interventions, appropriate management plans, and outcomes for both groups (PrD, SeD). Therefore, neuroimaging findings had a positive prognostic significance in the response to treatment in patients with primary dystonia compared with patients with secondary dystonia or distortion of basal ganglia anatomy. However, further studies in this line are warranted.

Actividad tripanocida y citotóxica de extractos de plantas colombianas / Trypanocidal and cytotoxic activity of extracts of Colombian plants

Introducción. El tratamiento de la enfermedad de Chagas está basado en sólo dos medicamentos de eficacia limitada y con importantes efectos colaterales. La gran biodiversidad de la flora colombiana hace de la bioprospección una alternativa potencial en la búsqueda de nuevos antiparasitarios. Objetivo. Evaluar in vitro el potencial tripanocida y la citotoxicidad de extractos obtenidos de 23 plantas colombianas. Materiales y métodos. Se obtuvieron extractos de hojas, de tallos o de la planta entera, en solventes de diferente polaridad. La actividad contra epimastigotes y la citotoxicidad se evaluaron por el micrométodo enzimático con MTT. Los extractos activos contra epimastigotes y con baja citotoxicidad se evaluaron también en tripomastigotes y amastigotes intracelulares. Resultados. Se reporta la actividad tripanocida de 13 plantas colombianas y se confirma el efecto biológico de cuatro especies previamente evaluadas. Cuatro extractos activos en epimastigotes también fueron activos en tripomastigotes y, uno de ellos, en amastigotes. Este extracto fue aislado de la planta Hieronyma antioquensis, y presentó CI50 de 3,125, 11,48 y 2,85 µg/ml, e índices de selectividad de 25,7 y 27, para epimastigotes, tripomastigotes y amastigotes, respectivamente. Los resultados sugieren que este extracto es un candidato promisorio para el tratamiento de la enfermedad de Chagas. Conclusión. La flora colombiana es una fuente potencial de nuevas sustancias para la quimioterapia contra la enfermedad de Chagas. El micrométodo enzimático con MTT es una herramienta útil para la tamización de la actividad biológica en epimastigotes y posterior selección para ensayos con otros estadios del parásito.

Introduction. The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs. Objective. Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants. Materials and methods. Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro-method. Extracts active against epimastigotes and with lowcytotoxicity were also tested on trypomastigotes and intracellular amastigotes. Results. Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC50 of 3.1 mg/ml for epimastigotes, 11.5mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively. Conclusions. The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials.

[Trypanocidal and cytotoxic activity of extracts of Colombian plants]. / Actividad tripanocida y citotóxica de extractos de plantas colombianas.

INTRODUCTION: The treatment of Chagas disease is based on only two drugs with limited efficacy and significant side effects. The rich biodiversity of the Colombian flora makes bio-prospecting a potential alternative in the search for new antiparasitic drugs. OBJECTIVE: Potential trypanocidal activity and cytotoxicity was assessed in extracts from 23 Colombian plants. MATERIALS AND METHODS: Extracts of leaves, stems, or of the whole plants were obtained in solvents of a range of polarities. The activity against Trypanosoma cruzi epimastigotes and the cytotoxicity were evaluated by the MTT enzymatic micro-method. Extracts active against epimastigotes and with low cytotoxicity were also tested on trypomastigotes and intracellular amastigotes. RESULTS: Among the extracts, biological activity was confirmed in 4 species. The extracts were active on epimastigotes and trypomastigotes; one was active also against amastigotes. The latter extract was isolated from the plant Hieronyma antioquensis and presented IC(50) of 3.1 mg/ml for epimastigotes, 11.5 mg/ml for trypomastigotes and 2.9 mg/ml for amastigotes. The selectivity indexes were 25, 7, and 27 respectively. CONCLUSIONS: The extract from H. antioquensis proved a promising candidate for Chagas disease treatment. Futhermore, the MTT enzymatic micromethod was a useful tool for screening biological activity on epimastigotes and other stages of the parasite for further extract trials.

Rapid differentiation of isobaric and positional isomers of structurally related glycosides from Phytolacca bogotensis.

Through the action of glycosyltransferases, a plant can biosynthetically assemble small different aglycons or 'templates' to various polysaccharides to produce numerous glycoconjugates differing in the type of the attached aglycon, the anomeric configuration of C-1 of the glycosylating sugar, the type of sugar and the different position of attachments of the sugar unit present in the polysaccharide chain. The position of attachments and the anomeric configuration of the different sugar present in the polysaccharide create the opportunity to generate molecules with either the same or very close molecular weights, which have relative structural similarity--forming isobaric and positional isomers. Although isomeric differentiation was once considered outside of the domain of mass spectrometry, this task can now be resolved using tandem mass spectrometry. In a standardized purified glycoconjugate fraction (SPT01) from Phytolacca bogotensis, we report conventional electrospray ionization mass spectrometry and collision-induced dissociation (CID) MS/MS parameters which favored the formation of characteristic product ions. This allowed us to suggest the type of sugar linkages present in a specific glycoconjugate. Ten new glycoconjugate are described from this plant and another twelve known saponins were structurally characterized using the automatic MSn acquisition mode. The differentiation of two pairs of positional isomers and four isobaric glycosides and the production of a library of 30 glycosides present in P. bogotensis were accomplished.

O-glycoside sequence of pentacyclic triterpene saponins from Phytolacca bogotensis using HPLC-ESI/multi-stage tandem mass spectrometry.

INTRODUCTION: The lack of pharmacopoeial methodologies for the quality control of plants used for therapeutic purposes is a huge problem that impacts directly upon public health. In the case of saponins, their great structural complexity, weak glycoside bonds and high polarity hinder their identification by conventional techniques. OBJECTIVE: To apply high-performance liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI/MS(n)) to identify the O-glycoside sequence of saponins from the roots of Phytolacca bogotensis. METHODOLOGY: Saponins were isolated by preparative HPLC and characterised by NMR spectroscopic experiments. Collision-induced dissociation (CID) of isolated saponins was performed producing typical degradation reactions that can be associated with several glycosidic bonds as empirical criteria. A method using solid-phase extraction (SPE) and HPLC/ESI-MS(n) for the characterisation of saponins and identification of novel molecules is described. RESULTS: Three saponins reported for the first time in P. bogotensis were isolated and characterised by NMR spectroscopy. Characteristic cross ring cleavage reactions have been used as empirical criteria for the characterisation of the glycosidic bonds most frequently reported for Phytolacca saponins. One new saponin was proposed on the basis of empirical criteria, and other five saponins were identified for the first time for P. bogotensis using HPLC-ESI/MS(n). CONCLUSION: Electrospray ionisation in combination with tandem mass spectrometry has been established as a powerful tool for the profiling of saponins from roots of P. bogotensis. CID proved to be a useful tool for the characterisation and identification of known and novel saponins from the plant family Phytolaccaceae and can be used for quality control purposes of crude plant extracts.

Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae.

Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25 microg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=10 and 16, respectively). The extracts from Desmopsis panamensis, Pseudomalmea boyacana, Rollinia exsucca and Rollinia pittieri showed good antiplasmodial activity (IC50 < 10 microg/ml). No correlation between antiplasmodial activity and inhibition of beta-hematin production was found. The present study gives specific and useful information about antiprotozoal and cytotoxic activities of some Annonaceae extracts. Results presented here also demonstrate which plants and/or plant parts could be useful in the treatment of leishmaniasis, Chagas' disease and malaria.

Antioxidant activity of isoflavones and biflavones isolated from Godoya antioquiensis.

Two biflavones, ochnaflavone (1) and 2",3"-dihydroochnaflavone (2), and two isoflavones, 5,7,4'-trihydroxy-3',5'-dimethoxyisoflavone (piscigenin) (3) and 5,4'-dihydroxy-7,3',5'-trimethoxyisoflavone (4), a new natural compound, were isolated from the leaves of Godoya antioquiensis (Ochnaceae). Their structures were determined on the basis of spectral data and by comparison with data reported in the literature. The isolated compounds were evaluated for their radical scavenging activity using the NBT (nitrobluetetrazolium)/hypoxanthine superoxide and the .OH/luminol chemiluminescence methods. The isolated isoflavones were found to exhibit a strong hydroxyl radical scavenging activity and a moderate inhibition of the superoxide anion, whereas the two biflavones were inactive in the superoxide anion assay and showed a low hydroxyl radical scavenging activity.

[Leishmania: role of P glycoprotein in drug resistance and reversion strategies]. / Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión.

Protozoan parasites are important causative agents of morbidity and mortality throughout the world--a problem further complicated by the emergence of drug resistance in these parasites. Mechanisms of drug resistance include the following: decreased uptake of the drug into the cell, loss of drug activation, alterations in the drug target, and over-expression of a well-known multiple drug transporter proteins. In this review, two critical components of resistance are stressed: (1) the role of ATP binding cassette proteins, such as P-glycoproteins, in mediating drug resistance in Leishmania and other protozoans, followed by development of cross-resistance to many structurally and functionally unrelated drugs, and (2) some concepts concerning the reversal mechanism of multidrug resistance by drugs and natural products. Several modulators or chemosensitizers alter the capacity of P-glycoproteins to maintain subtoxic intracellular drug concentrations. Calcium channel blockers such as verapamil act in this mode; however, high concentrations are required for an efficient and effective inhibition and, in addition, produce undesirable side effects. The discovery of new, natural product modulators of P-glycoproteins is stressed. This category of modulators offer potentially improved efficacy and lowered toxicity for the mammalian host.

Leishmania: papel de la glicoproteína P en la mediación de resistencia a medicamentos y estrategias de reversión / Leishmania: role of P glycoprotein in drug resistance and reversion strategies

Actualmente, los parásitos protozoarios son uno de los principales agentes causantes de morbilidad y mortalidad en el mundo, un problema complicado, además, por la aparición de resistencia a medicamentos en estos organismos. La resistencia a medicamentos observada en parásitos protozoarios se debe a diferentes mecanismos como la disminución de la entrada del medicamento a la célula por cambios en el transportador requerido, la pérdida de la activación del medicamento por parte del hospedero, las alteraciones en el blanco del medicamento y la expresión exagerada del transportador múltiple de medicamentos o glicoproteína P (Pgp). En esta revisión, nos centramos en: 1) el papel de las glicoproteínas P (Pgp) de la familia de proteínas ABC (ATP binding cassette) como los transportadores de múltiples medicamentos en la mediación de resistencia en protozoarios, especialmente en Leishmania, y en el desarrollo de resistencia cruzada para medicamentos estructural y funcionalmente no relacionados, y 2) en algunos conceptos relacionados con los mecanismos moduladores que podrían revertir la resistencia a medicamentos por fármacos y productos naturales. Numerosos moduladores o quimiosensibilizadores son conocidos por alterar la capacidad de las glicoproteínas P para mantener concentraciones intracelulares subtóxicas del medicamento; algunos ejemplos incluyen los bloqueadores de los canales de calcio como el verapamilo; sin embargo, se requieren altas concentraciones para una inhibición eficiente y duradera, las cuales producen efectos adversos indeseables. Por tanto, se necesitan más investigaciones relacionadas con los moduladores naturales para Pgp, los cuales podrían presentar menor toxicidad para el hospedero

In vitro and in vivo cytotoxicities and antileishmanial activities of thymol and hemisynthetic derivatives.

The in vitro and in vivo antileishmanial and cytotoxic activities of thymol and structural derivatives in comparison to those of Glucantime were studied. The results showed here suggest that thymol and hemisynthetic derivatives have promising antileishmanial potential and could be considered as new lead structures in the search for novel antileishmanial drugs.

Epilepsia y mujer adolescente / Epilepsy and adolescent woman

La mujer adolescente con epilepsia tiene una serie de características especiales que hacen que su manejo requiera un enfoque único y personalizado. A esta edad suelen iniciar los tipos más importantes de epilepsias primarias que van requerir tratamiento a largo plazo. Los efectos secundarios e interacciones de los medicamentos antiepilépticos pueden afectar los ciclos reproductivos con infertilidad secundaria, el equilibrio hormonal (síndrome de ovario poliquístico), generar osteoporosis, aumento de peso, cambios estéticos, etc que tienen un impacto considerable en esta crítica etapa de la vida. A pesar de todo es posible ofrecer a este grupo una terapia adecuada, con el objetivo de llevar una vida normal

Angiotensin-converting enzyme and alpha-2-macroglobulin gene polymorphisms are not associated with Alzheimer's disease in Colombian patients.

Polymorphisms in alpha-2-macroglobulin (A2M) and angiotensin-converting enzyme (ACE) genes have been considered as risk factors for Alzheimer's disease (AD) independently of the risk conferred by the apolipoprotein E sigma4 allele (APOEsigma4) in diverse populations. In the present study, we have analysed the distribution of genotypes and alleles of the insertion/deletion (I/D) polymorphisms of ACE and A2M in 83 AD patients and 69 normal controls in Colombia. Our results showed that there is no association between the I/D polymorphisms of ACE and A2M with AD (P = 0.788 and P = 0.538, respectively). Using logistic regression and multiple correlation analysis (MCA), we confirmed that the main risk factor associated and consistently grouped with AD patients in this population is APOE4, but this association was not observed with alleles and genotypes of ACE and A2M.

Haplogroup analysis of the risk associated with APOE promoter polymorphisms (-219T/G, -491A/T and -427T/C) in Colombian Alzheimer's disease patients.

Results analyzing the association between polymorphisms in the promoter region of the apolipoprotein E (APOE) gene and Alzheimer's disease (AD) are contradictory. We studied the association of three polymorphisms in the APOE promoter (-219T/G, -491A/T and -427T/C) with AD in a sample of the Colombian population. The polymorphism -491A/T confers increased risk for AD associated with AA genotype independent of APOEe4 allele (odds ratio (OR): 2.64) and more pronounced in men (OR: 6.07). Genotypes TT and TG of -219T/G showed a significant association with AD, but this was lost in an adjusted model. We did not find any association with -427T/C polymorphism. Using a haplogroup analysis of the promoter polymorphisms, we further confirmed their independent contribution as genetic risk factors for AD.