RESUMEN
Choroideremia (CHM) is an X-linked chorioretinal dystrophy leading to progressive retinal degeneration that results in blindness by late adulthood. It is caused by mutations in the CHM gene encoding the Rab Escort Protein 1 (REP1), which plays a crucial role in the prenylation of Rab proteins ensuring correct intracellular trafficking. Gene augmentation is a promising therapeutic strategy, and there are several completed and ongoing clinical trials for treating CHM using adeno-associated virus (AAV) vectors. However, late-phase trials have failed to show significant functional improvements and have raised safety concerns about inflammatory events potentially caused by the use of viruses. Therefore, alternative non-viral therapies are desirable. Episomal scaffold/matrix attachment region (S/MAR)-based plasmid vectors were generated containing the human CHM coding sequence, a GFP reporter gene, and ubiquitous promoters (pS/MAR-CHM). The vectors were assessed in two choroideremia disease model systems: (1) CHM patient-derived fibroblasts and (2) chmru848 zebrafish, using Western blotting to detect REP1 protein expression and in vitro prenylation assays to assess the rescue of prenylation function. Retinal immunohistochemistry was used to investigate vector expression and photoreceptor morphology in injected zebrafish retinas. The pS/MAR-CHM vectors generated persistent REP1 expression in CHM patient fibroblasts and showed a significant rescue of prenylation function by 75%, indicating correction of the underlying biochemical defect associated with CHM. In addition, GFP and human REP1 expression were detected in zebrafish microinjected with the pS/MAR-CHM at the one-cell stage. Injected chmru848 zebrafish showed increased survival, prenylation function, and improved retinal photoreceptor morphology. Non-viral S/MAR vectors show promise as a potential gene-augmentation strategy without the use of immunogenic viral components, which could be applicable to many inherited retinal disease genes.
Asunto(s)
Coroideremia , Distrofias Retinianas , Animales , Humanos , Adulto , Coroideremia/genética , Coroideremia/terapia , Coroideremia/metabolismo , Pez Cebra/genética , Pez Cebra/metabolismo , Retina/metabolismo , Mutación , Distrofias Retinianas/metabolismo , Plásmidos , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
USH2A mutations are a common cause of autosomal recessive retinitis pigmentosa (RP) and Usher syndrome, for which there are currently no approved treatments. Gene augmentation is a valuable therapeutic strategy for treating many inherited retinal diseases; however, conventional adeno-associated virus (AAV) gene therapy cannot accommodate cDNAs exceeding 4.7 kb, such as the 15.6-kb-long USH2A coding sequence. In the present study, we adopted an alternative strategy to successfully generate scaffold/matrix attachment region (S/MAR) DNA plasmid vectors containing the full-length human USH2A coding sequence, a GFP reporter gene, and a ubiquitous promoter (CMV or CAG), reaching a size of approximately 23 kb. We assessed the vectors in transfected HEK293 cells and USH2A patient-derived dermal fibroblasts in addition to ush2au507 zebrafish microinjected with the vector at the one-cell stage. pS/MAR-USH2A vectors drove persistent transgene expression in patient fibroblasts with restoration of usherin. Twelve months of GFP expression was detected in the photoreceptor cells, with rescue of Usher 2 complex localization in the photoreceptors of ush2au507 zebrafish retinas injected with pS/MAR-USH2A. To our knowledge, this is the first reported vector that can be used to express full-length usherin with functional rescue. S/MAR DNA vectors have shown promise as a novel non-viral retinal gene therapy, warranting further translational development.
Asunto(s)
Síndromes de Usher , Animales , Humanos , Síndromes de Usher/genética , Síndromes de Usher/terapia , Pez Cebra/genética , Células HEK293 , Mutación , ADN , Plásmidos/genética , Proteínas de la Matriz Extracelular/genéticaRESUMEN
AIM: To evaluate the chemotherapeutic potential of a novel multifunctional nanocomposite encapsulating both porous silicon (PSi) and gold (Au) nanoparticles in a polymeric nanocomplex. MATERIALS & METHODS: The nanocomposite was physicochemically characterized and evaluated in vitro for biocompatibility, cellular internalization, endosomolytic properties, cytoplasmatic drug delivery and chemotherapeutic efficacy. RESULTS: The nanocomposites were successfully produced and exhibited adequate physicochemical properties and superior in vitro cyto- and hemocompatibilities. The encapsulation of PSi nanoparticles in the nanocomplexes significantly enhanced their cellular internalization and enabled their endosomal escape, resulting in the efficient cytoplasmic delivery of these nanosystems. Sorafenib-loaded nanocomposites showed a potent in vitro antiproliferative effect on MDA-MB-231 breast cancer cells. CONCLUSION: The multifunctional nanocomposite herein presented exhibits great potential as a chemotherapeutic nanoplatform.
RESUMEN
Bioresponsive cytosolic nanobased multidelivery has been emerging as an enormously challenging novel concept due to the intrinsic protective barriers of the cells and hardly controllable performances of nanomaterials. Here, we present a new paradigm to advance nano-in-nano integration technology amenable to create multifunctional nanovehicles showing considerable promise to overcome restrictions of intracellular delivery, solve impediments of endosomal localization and aid effectual tracking of nanoparticles. A redox responsive intercalator chemistry comprised of cystine and 9-aminoacridine is designed as a cross-linker to cap carboxylated porous silicon nanoparticles with DNA. These intelligent nanocarriers are then encapsulated within novel one-pot electrostatically complexed nano-networks made of a zwitterionic amino acid (cysteine), an anionic bioadhesive polymer (poly(methyl vinyl ether-alt-maleic acid)) and a cationic endosomolytic polymer (polyethyleneimine). This combined nanocomposite is successfully tested for the co-delivery of hydrophobic (sorafenib) or hydrophilic (calcein) molecules loaded within the porous core, and an imaging agent covalently integrated into the polyplex shell by click chemistry. High loading capacity, low cyto- and hemo-toxicity, glutathione responsive on-command drug release, and superior cytosolic delivery are shown as achievable key features of the proposed formulation. Overall, formulating drug molecules, DNA and imaging agents, without any interference, in a physico-chemically optimized carrier may open a path towards broad applicability of these cost-effective multivalent nanocomposites for treating different diseases.
Asunto(s)
ADN/química , Preparaciones de Acción Retardada/química , Anhídridos Maleicos/química , Nanopartículas/química , Polietileneimina/química , Polivinilos/química , Silicio/química , Antineoplásicos/administración & dosificación , Línea Celular , Química Clic , Reactivos de Enlaces Cruzados/química , Liberación de Fármacos , Fluoresceínas/administración & dosificación , Colorantes Fluorescentes/administración & dosificación , Humanos , Nanocompuestos/química , Nanocompuestos/ultraestructura , Nanopartículas/ultraestructura , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Oxidación-Reducción , Compuestos de Fenilurea/administración & dosificación , Porosidad , SorafenibRESUMEN
Chronic heart failure, predominantly developed after myocardial infarction, is a leading cause of high mortality worldwide. As existing therapies have still limited success, natural and/or synthetic nanomaterials are emerging alternatives for the therapy of heart diseases. Therefore, we aimed to functionalize undecylenic acid thermally hydrocarbonized porous silicon nanoparticles (NPs) with different targeting peptides to improve the NP's accumulation in different cardiac cells (primary cardiomyocytes, non-myocytes, and H9c2 cardiomyoblasts), additionally to investigate the behavior of the heart-targeted NPs in vivo. The toxicity profiles of the NPs evaluated in the three heart-type cells showed low toxicity at concentrations up to 50 µg/mL. Qualitative and quantitative cellular uptake revealed a significant increase in the accumulation of atrial natriuretic peptide (ANP)-modified NPs in primary cardiomyocytes, non-myocytes and H9c2 cells, and in hypoxic primary cardiomyocytes and non-myocytes. Competitive uptake studies in primary cardiomyocytes showed the internalization of ANP-modified NPs takes place via the guanylate cyclase-A receptor. When a myocardial infarction rat model was induced by isoprenaline and the peptide-modified [(111)In]NPs administered intravenously, the targeting peptides, particularly peptide 2, improved the NPs' accumulation in the heart up to 3.0-fold, at 10 min. This study highlights the potential of these peptide-modified nanosystems for future applications in heart diseases.
Asunto(s)
Corazón/fisiología , Nanopartículas/química , Silicio/química , Adsorción , Animales , Factor Natriurético Atrial/metabolismo , Proteínas Sanguíneas/metabolismo , Supervivencia Celular , Coloides , Humanos , Masculino , Miocitos Cardíacos/metabolismo , Nanopartículas/ultraestructura , Péptidos/química , Porosidad , Ratas Wistar , Temperatura , Tomografía Computarizada de Emisión de Fotón Único , Ácidos Undecilénicos/químicaRESUMEN
The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.
Asunto(s)
Biopolímeros/química , Portadores de Fármacos/química , Silicio/química , Cicatrización de Heridas/efectos de los fármacos , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Línea Celular , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Liberación de Fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Humanos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Porosidad , Especies Reactivas de Oxígeno/metabolismo , Resveratrol , Espectroscopía Infrarroja por Transformada de Fourier , Estilbenos/administración & dosificación , Estilbenos/uso terapéutico , Vancomicina/administración & dosificación , Vancomicina/uso terapéuticoRESUMEN
Active targeting of nanoparticles to receptor-overexpressing cancer cells has great potential for enhancing the cellular uptake of nanoparticles and for reducing fast clearance of the nanoparticles from the body. Herein, we present a preparation method of a porous silicon (PSi)-based nanodelivery system for breast cancer targeting, by covalently conjugating a synthesized amide-modified hyaluronic acid (HA(+)) derived polymer on the surface of undecylenic acid-modified thermally hydrocarbonized PSi (UnTHCPSi) nanoparticles. The resulting UnTHCPSi-HA(+) nanoparticles showed relatively small size, reduced polydispersibility, high biocompatibility, improved colloidal and human plasma stability, as well as enhanced cellular interactions and internalization. Moreover, we demonstrated that the enhanced cellular association of UnTHCPSi-HA(+) relies on the capability of the conjugated HA(+) to bind and consequently target CD44 receptors expressed on the surface of breast cancer cells, thus making the HA(+)-functionalized UnTHCPSi nanoparticles a suitable and promising nanoplatform for the targeting of CD44-overexpressing breast tumors and for drug delivery.
Asunto(s)
Aminas Biogénicas/farmacocinética , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Ácido Hialurónico/química , Nanocápsulas/química , Silicio/química , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Aminas Biogénicas/química , Neoplasias de la Mama/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Difusión , Composición de Medicamentos/métodos , Humanos , Ensayo de Materiales , Nanocápsulas/administración & dosificación , Nanoconjugados , Nanoporos/ultraestructura , Tamaño de la Partícula , Porosidad , Resultado del TratamientoRESUMEN
The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.
Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/metabolismo , Endosomas/metabolismo , Maleatos/metabolismo , Metotrexato/administración & dosificación , Nanopartículas/metabolismo , Polietileneimina/metabolismo , Polietilenos/metabolismo , Antimetabolitos Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Preparaciones de Acción Retardada/química , Femenino , Humanos , Iones/química , Iones/metabolismo , Células MCF-7 , Maleatos/química , Metotrexato/farmacología , Nanopartículas/química , Nanopartículas/ultraestructura , Polietileneimina/química , Polietilenos/química , Polímeros , Porosidad , Silicio , Propiedades de SuperficieRESUMEN
Currently, developing a stable nanocarrier with high cellular internalization and low toxicity is a key bottleneck in nanomedicine. Here, we have developed a successful method to covalently conjugate poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of (3-aminopropyl)triethoxysilane-functionalized thermally carbonized porous silicon nanoparticles (APSTCPSi NPs), forming a surface negatively charged nanovehicle with unique properties. This polymer conjugated NPs could modify surface smoothness, charge, and hydrophilicity of the developed NPs, leading to considerable improvement in the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the polymer-conjugated NPs, the cellular internalization was increased in both MDA-MB-231 and MCF-7 breast cancer cells. These results provide a proof-of-concept evidence that such polymer-based PSi nanocomposite can be extensively used as a promising candidate for intracellular drug delivery.
Asunto(s)
Células/citología , Nanopartículas/química , Polímeros/química , Silicio/química , Adhesión Celular , Línea Celular Tumoral , Supervivencia Celular , Humanos , PorosidadRESUMEN
BACKGROUND: Insecticide-treated bed nets (ITN) reduce malaria morbidity and mortality consistently in Africa, but their benefits have been less consistent in Asia. This study's objective was to evaluate the malaria protective efficacy of village-wide usage of ITN in Western Myanmar and estimate the cost-effectiveness of ITN compared with extending early diagnosis and treatment services. METHODS: A cluster-randomized controlled trial was conducted in Rakhine State to assess the efficacy of ITNs in preventing malaria and anaemia in children and their secondary effects on nutrition and development. The data were aggregated for each village to obtain cluster-level infection rates. In total 8,175 children under 10 years of age were followed up for 10 months, which included the main malaria transmission period. The incidence and prevalence of Plasmodium falciparum and Plasmodium vivax infections, and the biting behaviour of Anopheles mosquitoes in the area were studied concurrently. The trial data along with costs for current recommended treatment practices were modelled to estimate the cost-effectiveness of ITNs compared with, or in addition to extending the coverage of early diagnosis and treatment services. RESULTS: In aggregate, malaria infections, spleen rates, haemoglobin concentrations, and weight for height, did not differ significantly during the study period between villages with and without ITNs, with a weighted mean difference of -2.6 P. falciparum episodes per 1,000 weeks at risk (95% Confidence Interval -7 to 1.8). In areas with a higher incidence of malaria there was some evidence ITN protective efficacy. The economic analysis indicated that, despite the uncertainty and variability in their protective efficacy in the different study sites, ITN could still be cost-effective, but not if they displaced funding for early diagnosis and effective treatment which is substantially more cost-effective. CONCLUSION: In Western Myanmar deployment of ITNs did not provide consistent protection against malaria in children living in malaria endemic villages. Early diagnosis and effective treatment is a more cost effective malaria control strategy than deployment of ITNs in this area where the main vector bites early in the evening, often before people are protected by an ITN.
Asunto(s)
Anopheles/fisiología , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Malaria Falciparum/epidemiología , Malaria Falciparum/prevención & control , Malaria Vivax/epidemiología , Malaria Vivax/prevención & control , Control de Mosquitos/métodos , Animales , Antimaláricos/uso terapéutico , Niño , Preescolar , Análisis Costo-Beneficio , Estudios Transversales , Diagnóstico Precoz , Conducta Alimentaria , Humanos , Incidencia , Lactante , Recién Nacido , Mosquiteros Tratados con Insecticida/economía , Masculino , Control de Mosquitos/economía , Mianmar/epidemiología , PrevalenciaRESUMEN
BACKGROUND: In a large cluster randomized control trial of insecticide-treated bed nets (ITN) in Western Myanmar the malaria protective effect of ITN was found to be highly variable and, in aggregate, the effect was not statistically significant. A coincident entomological investigation measured malaria vector abundance and biting behaviour and the human population sleeping habits, factors relevant to ITN effectiveness. METHODS: Entomological surveys were carried out using different catching methods to identify potential malaria vector species and characterise their biting habits. The salivary glands were dissected from all female anophelines caught to identify sporozoites by microscopy. FINDINGS: Between 1995 and 2000 a total of 4,824 female anopheline mosquitoes were caught with various catching methods. A total of 916 person nights yielded 3,009 female anopheline mosquitoes between 6 pm and 6 am. Except for Anopheles annularis, which showed no apparent preference (51% outdoor biting), all major species showed a strong preference for outdoor biting; Anopheles epiroticus (79%), Anopheles subpictus (72%), Anopheles maculatus (92%), Anopheles aconitus (85%) and Anopheles vagus (72%). Most human biting occurred in the early evening with the peak biting time between 6 pm and 7 pm (35%). Overall 51% (1447/2837) of all bites recorded were between 6 pm and 8 pm. A large proportion of children were not sleeping under an ITN during peak biting times. Only one An. annularis mosquito (0.02%) had malaria sporozoites identified in the salivary glands. CONCLUSIONS: Peak vector biting occurred early in the evening and mainly occurred outdoors. The limited efficacy of ITN in this area of Western Myanmar may be explained by the biting behaviour of the prevalent Anopheles mosquito vectors in this area.
Asunto(s)
Anopheles/fisiología , Mosquiteros Tratados con Insecticida/estadística & datos numéricos , Malaria/prevención & control , Control de Mosquitos/métodos , Animales , Anopheles/parasitología , Niño , Preescolar , Conducta Alimentaria , Femenino , Humanos , Lactante , Recién Nacido , Malaria/epidemiología , Masculino , Microscopía , Mianmar/epidemiología , Plasmodium/aislamiento & purificación , Glándulas Salivales/parasitologíaRESUMEN
Despite steadily increasing insights on the biocompatibility of PSi nanoparticles (NPs), an extensive biosafety study on the immune and red blood cells (RBCs) is still lacking. Herein, we evaluated the impact of the PSi NPs' surface chemistry on immune cells and human RBCs both in vitro and in vivo. Negatively charged hydrophilic and hydrophobic PSi NPs caused less ATP depletion and genotoxicity than the positively charged amine modified hydrophilic PSi NPs, demonstrating the main role of PSi NPs' surface charge on the immunocompatibility profile. Furthermore, cells with lower metabolic activity, longer doubling time, and shorter half-life were more sensitive to the concentration- and time-dependent toxicity in the following order: T-cells ≈ monocytes > macrophages ≈ B-cells. RBC hemolysis and imaging assay revealed a significant correlation between the surface chemistry, the amount of the PSi NPs adsorbed on the cell surface and the extent of morphological changes. The in vivo results showed that despite mild renal steatosis, glomerular degeneration, hepatic central vein dilation and white pulp shrinkage in spleen, no notable changes were observed in the serum level of biochemical and hematological factors. This study is a comprehensive demonstration of the mechanistic direct and indirect genotoxicity effects of PSi NPs, elucidating the most influencing properties for the PSi NPs' design.
Asunto(s)
Eritrocitos/efectos de los fármacos , Nanopartículas/efectos adversos , Nanopartículas/química , Silicio/química , Animales , Linfocitos B/citología , Linfocitos B/efectos de los fármacos , Linfocitos B/ultraestructura , Línea Celular , Eritrocitos/citología , Eritrocitos/ultraestructura , Hemólisis/efectos de los fármacos , Humanos , Masculino , Ratones , Microscopía Electroquímica de Rastreo , Nanopartículas/ultraestructura , Ratas , Ratas Sprague-DawleyRESUMEN
O artigo busca desenvolver reflexões sobre a questão do delírio de influência na esquizofrenia a partir de casos clássicos da história da psicanálise - apresentados sobretudo por Victor Tausk, assim como por S. Freud e Margaret Mahler - colocando em evidência a relação da máquina ao corpo do psicótico, tentando assim tecer considerações a partir da teoria lacaniana para realizar uma leitura atualizada destes casos: uma vez que a compensação imaginária não opera mais para esses sujeitos, tem-se então psicóticos sobre influência, seja por máquinas, seja por um semelhante - consequência direta sobre o corpo e seus orgãos da foraclusão da significação fálica.(AU)
The article seeks to develop some reflections on the question of the delirium of influence in schizophrenia cases from the history of classical psychoanalysis presented by Victor Tausk, S. Freud and Margaret Mahler - bringing to the light the relationship of the machine to the body of psychotic, trying to develop some considerations from the lacanian theory to perform an updated reading of these cases, since the compensation does not any more operate for these subjects, we have an psychotic under influence either by machines or by a similar - direct consequence on the body and its organs of forclusion of phallic signification.(AU)
El artículo tiene por objeto desarrollar las reflexiones sobre la cuestión del delirio de la influencia en los casos de esquizofrenia de la historia del psicoanálisis clásico, en especial presentado por Victor Tausk, y S. Freud y Margaret Mahler - sacando a la luz la relación de la máquina para el cuerpo de psicóticos, tratando de desarrollar algunas consideraciones de la teoría lacaniana para realizar une lectura actualizada de estos casos, ya que la compensación no opera más de imaginar en estos sujetos, hemos para psicóticos sobre la influencia, ya sea por máquinas o por une similar - consecuencia directa sobre el cuerpo y sus órganos de ejecución de une forclusion de la significación fálica.(AU)
Asunto(s)
Esquizofrenia/patología , Esquizofrenia/terapia , Delirio/psicología , Teoría Psicoanalítica , Teoría FreudianaRESUMEN
O artigo busca desenvolver reflexões sobre a questão do delírio de influência na esquizofrenia a partir de casos clássicos da história da psicanálise - apresentados sobretudo por Victor Tausk, assim como por S. Freud e Margaret Mahler - colocando em evidência a relação da máquina ao corpo do psicótico, tentando assim tecer considerações a partir da teoria lacaniana para realizar uma leitura atualizada destes casos: uma vez que a compensação imaginária não opera mais para esses sujeitos, tem-se então psicóticos sobre influência, seja por máquinas, seja por um semelhante - consequência direta sobre o corpo e seus orgãos da foraclusão da significação fálica.
The article seeks to develop some reflections on the question of the delirium of influence in schizophrenia cases from the history of classical psychoanalysis presented by Victor Tausk, S. Freud and Margaret Mahler - bringing to the light the relationship of the machine to the body of psychotic, trying to develop some considerations from the lacanian theory to perform an updated reading of these cases, since the compensation does not any more operate for these subjects, we have an psychotic under influence either by machines or by a similar - direct consequence on the body and its organs of forclusion of phallic signification.
El artículo tiene por objeto desarrollar las reflexiones sobre la cuestión del delirio de la influencia en los casos de esquizofrenia de la historia del psicoanálisis clásico, en especial presentado por Victor Tausk, y S. Freud y Margaret Mahler - sacando a la luz la relación de la máquina para el cuerpo de psicóticos, tratando de desarrollar algunas consideraciones de la teoría lacaniana para realizar une lectura actualizada de estos casos, ya que la compensación no opera más de imaginar en estos sujetos, hemos para psicóticos sobre la influencia, ya sea por máquinas o por une similar - consecuencia directa sobre el cuerpo y sus órganos de ejecución de une forclusion de la significación fálica.