44 research outputs found
Can a systems approach produce a better understanding of mood disorders?
Background: One in twenty-five people suffer from a mood disorder. Current treatments are sub-optimal with poor patient response and uncertain modes-of-action. There is thus a need to better understand underlying mechanisms that determine mood, and how these go wrong in affective disorders. Systems biology approaches have yielded important biological discoveries for other complex diseases such as cancer, and their potential in affective disorders will be reviewed. Scope of review: This review will provide a general background to affective disorders, plus an outline of experimental and computational systems biology. The current application of these approaches in understanding affective disorders will be considered, and future recommendations made. Major conclusions: Experimental systems biology has been applied to the study of affective disorders, especially at the genome and transcriptomic levels. However, data generation has been slowed by a lack of human tissue or suitable animal models. At present, computational systems biology has only be applied to understanding affective disorders on a few occasions. These studies provide sufficient novel biological insight to motivate further use of computational biology in this field. General significance: In common with many complex diseases much time and money has been spent on the generation of large-scale experimental datasets. The next step is to use the emerging computational approaches, predominantly developed in the field of oncology, to leverage the most biological insight from these datasets. This will lead to the critical breakthroughs required for more effective diagnosis, stratification and treatment of affective disorders
Identification and characterization of forced degradation products of paliperidone using LC鈥揂PCI鈥揑on Trap鈥揗S
ANHIDRASA CARB脫NICA DE Plasmodium falciparum: UN BLANCO 脷TIL PARA EL DISE脩O DE MEDICAMENTOS ANTIMAL脕RICOS Y COMPUESTOS BLOQUEADORES DE LA TRANSMISI脫N DE MALARIA CARBONIC ANHYDRASE IN Plasmodium falciparum: A USEFUL TARGET FOR ANTIMALARIAL DRUG DESIGNING AND MALARIA BLOCKING TRANSMISSION COMPOUNDS
La anhidrasa carb贸nica es una metaloenzima que cataliza la conversi贸n reversible del CO2 a bicarbonato, un componente metab贸lico indispensable para la s铆ntesis de pirimidinas de novo por Plasmodium spp y los procesos de exflagelaci贸n llevados a cabo por el par谩sito al interior del mosquito vector. La enzima participa adem谩s en el transporte del bicarbonato dentro y fuera de las c茅lulas para evitar un desequilibrio en el sistema CO2/HCO3- y la alteraci贸n del pH al interior de las c茅lulas y en el espacio intercelular. Por lo tanto, al inhibir la enzima, ya sea en el par谩sito o en el insecto vector, se podr铆a conducir a una disminuci贸n de la replicaci贸n y al detrimento y/o muerte del par谩sito. De esta forma, los inhibidores de anhidrasa carb贸nica constituyen una alternativa, tanto terap茅utica como de bloqueo de la transmisi贸n, para el control de la malaria. La actividad anti-Plasmodium in vitro de algunos compuestos inhibidores de anhidrasa carb贸nica ya se ha determinado. Sin embargo, la eficacia in vivo y el mecanismo por el cual los inhibidores son capaces de afectar el desarrollo del par谩sito en los mosquitos vectores permanecen a煤n por evaluarse. En el marco del proyecto de investigaci贸n "Evaluaci贸n de inhibidores de anhidrasa carb贸nica como medidas terap茅uticas y de bloqueo de la transmisi贸n de malaria" este art铆culo presenta una revisi贸n del estado del arte sobre el papel de la anhidrasa carb贸nica de Plasmodium spp y el uso de inhibidores espec铆ficos de esta enzima como una estrategia para el tratamiento de la malaria y el bloqueo de la transmisi贸n de la enfermedad. Se incluyeron art铆culos publicados en los 煤ltimos 59 a帽os, identificados a partir de la bases de datos bibliogr谩ficos PubMed y ScienceDirect, cruzando las palabras claves, al igual que art铆culos recopilados por los autores y se analizan e integran los resultados de investigaciones publicadas alrededor del tema.Carbonic anhydrase is a metalloenzyme that catalyzes the reversible conversion of CO2 to bicarbonate, an essential metabolic component used by the malaria parasites for de novo synthesis of pyrimidines and the exflagelation of gametocytes inside the mosquito vector. Carbonic anhydrase is involved in the transport of bicarbonate. This enzyme participates in transport of bicarbonate inside and outside the cells to avoid an imbalance in the system CO2/HCO3- and alteration of pH in the interior of the cell as well as in the intercellular space. Therefore, inhibition of this enzyme either in the parasite or the insect vector, could lead to a decrease in replication and to the detriment and/or death of the parasite. Given the importance of carbonic anhydrase in the metabolism, development and survival of Plasmodium, it could be postulated that carbonic anhydrase inhibitors are both a therapeutic and a blocking transmission alternative. Previous studies have demonstrated the in vitro anti-Plasmodium activity of some inhibitors. However, it is necessary to determine their effectiveness to confirm its usefulness in the treatment or blocking malaria transmission and the mechanism by which these inhibitors are able to affect the development of the parasite in the mosquito vector. In this paper we present a review about the role of carbonic anhydrase in Plasmodium spp and using some specific inhibitors as a strategy for malaria treatment and transmission blocking strategy. Articles published in the past 59 years identified from bibliographic database (PubMed and ScienceDirect) and papers collected by the authors were included
Risperidone reverses the spatial object recognition impairment and hippocampal BDNF-TrkB signalling system alterations induced by acute MK-801 treatment
An Improved and Efficient Process for the Production of Highly Pure Paliperidone, a Psychotropic Agent, via DBU Catalyzed N
New model of action for mood stabilizers: phosphoproteome from rat pre-frontal cortex synaptoneurosomal preparations.
BACKGROUND: Mitochondrial short and long-range movements are necessary to generate the energy needed for synaptic signaling and plasticity. Therefore, an effective mechanism to transport and anchor mitochondria to pre- and post-synaptic terminals is as important as functional mitochondria in neuronal firing. Mitochondrial movement range is regulated by phosphorylation of cytoskeletal and motor proteins in addition to changes in mitochondrial membrane potential. Movement direction is regulated by serotonin and dopamine levels. However, data on mitochondrial movement defects and their involvement in defective signaling and neuroplasticity in relationship with mood disorders is scarce. We have previously reported the effects of lithium, valproate and a new antipsychotic, paliperidone on protein expression levels at the synaptic level. HYPOTHESIS: Mitochondrial function defects have recently been implicated in schizophrenia and bipolar disorder. We postulate that mood stabilizer treatment has a profound effect on mitochondrial function, synaptic plasticity, mitochondrial migration and direction of movement. METHODS: Synaptoneurosomal preparations from rat pre-frontal cortex were obtained after 28 daily intraperitoneal injections of lithium, valproate and paliperidone. Phosphorylated proteins were identified using 2D-DIGE and nano LC-ESI tandem mass spectrometry. RESULTS: Lithium, valproate and paliperidone had a substantial and common effect on the phosphorylation state of specific actin, tubulin and myosin isoforms as well as other proteins associated with neurofilaments. Furthermore, different subunits from complex III and V of the electron transfer chain were heavily phosphorylated by treatment with these drugs indicating selective phosphorylation. CONCLUSIONS: Mood stabilizers have an effect on mitochondrial function, mitochondrial movement and the direction of this movement. The implications of these findings will contribute to novel insights regarding clinical treatment and the mode of action of these drugs