Functional analysis of gene expression in risperidone treated cells provide new insights in molecular mechanism and new candidate genes for pharmacogenetic studies

Risperidone is a potent antagonist of both dopamine and serotonin receptors. However, little is known about the underlying molecular mechanism by which risperidone acts. Although a number of genetic variants have been observed to correlate with treatment response there are no definitive predictors of response. We performed a genome-wide gene expression analysis (Human Genome U219 Array Plate) of a human neuroblastoma cell line (SK-N-SH) exposed to risperidone to identify molecular mechanisms involved in the cellular response to risperidone and thus identify candidate genes for pharmacogenetic studies. Our results revealed that cellular risperidone treatment is associated with a range of gene expression changes, which are time (6–48 h) and dose related (0.1–10 μM). We found that functional clusters of these changes correspond to Gene Ontology categories related to neural cell development functions, and synaptic structure and functions. We also identified Canonical Pathways related to these functional categories: neurogenesis and axon guidance; synaptic vesicle; and neurotransmitter signaling (dopamine, serotonin and glutamate). Finally, we identified candidate genes for pharmacogenetic studies related to the main risperidone secondary effects: motor disorders, cardiovascular disorders and metabolic disorders. Our results suggest that risperidone treatment affects the neurogenesis and neurotransmission of neuroblastoma cells, which is in agreement with the “initiation and adaptation” model to explain the mechanism of action of psychotropic drugs.     

A New Method to Detect Directly in Culture Cell Surface Membrane Immunoglobulins

Abstract

An ELISA assay is described for the measurement of the smIgG. The method is based on the detection of cell-smIgG directly on the same microplate used for the culture. The cells, preincubated at 37°C for one hour, were cultured in the presence of S-ConA and serum-free medium for two days. Using this strategy, the background noise due to non specific adsorbtion of IgG to plastic wells and cytophilic antibodies was eliminated. The cells in the presence of S-ConA and serum-free medium adhered to the plastic wells, and the cell-smIgG were detected using an anti-human IgG covalently linked to alkaline phosphatase or its F(ab')₂ fragment. The possibility of measuring the modulation of the expression of the cell-smIgG without any additional manipulation is stressed.     

Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial

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Preliminary Evaluation of the Safety and Efficacy of Standard Intravenous Immunoglobulins in Pregnant Women with Primary Cytomegalovirus Infection

Hyperimmune globulins were reported to prevent and treat fetal cytomegalovirus (CMV) infection during pregnancy. Here, we report that infusions of standard human intravenous immunoglobulin significantly increase CMV IgG titers and avidity indexes in pregnant women, paving the way to their use for passive transfer of maternal CMV humoral immunity to fetuses. Preliminary data on perinatal outcomes of the first 67 newborns are encouraging.     

Comments on potential efficacy of monthly administrations of spot-on moxidectin 2.5 %/imidacloprid 10 % in the simultaneous prevention of major canine filarioses

Information on the efficacy of pharmaceutical protocols for the prevention of the major canine filarioses (i.e., Dirofilaria immitis, Dirofilaria repens, and Acanthocheilonema reconditum) under natural conditions is scant. Chemoprophylaxis for canine filarioses under field conditions deserves to be studied more fully and information about vector biology, ecology, and seasonality has to be well appreciated to correctly set control protocols. It is advisable that researchers planning field trials to assess the efficacy of any product for the prevention of canine vector-borne diseases should consider different eco-epidemiological aspects of diseases, including their dynamics of transmission, which are driven by complex interactions between animals, pathogens, and vectors.