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1 | Pharmacopsychiatry 2000 Nov 33: 218-20 |
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PMID | 11147929 |
Title | Clozapine-induced agranulocytosis and hereditary polymorphisms of clozapine metabolizing enzymes: no association with myeloperoxidase and cytochrome P4502D6. |
Abstract | The pathomechanisms of most drug-induced agranulocytoses are unclear; however, there are some studies pointing to genetic determinants. Some drug-induced agranulocytoses such as clozapine-induced agranulocytosis (CA) may be regarded as an idiosyncratic drug reaction because of its preclinical and clinical characteristics. To study some aspects of the genetic background of CA further, polymorphisms of specific metabolizing enzyme systems of clozapine were examined. Thirty-one schizophrenic patients with CA and 77 schizophrenic comparison subjects without this adverse effect underwent genotyping of a recently discovered G(-463)A polymorphism of myeloperoxidase (MPO) gene and cytochrome P4502D6. Neither the MPO mutation nor specific genotypes of cytochrome P4502D6 were associated with CA. Both were equally distributed among CA patients and controls. Thus, our data suggest lack of evidence of an association of CA and genetically variable activity of these specific drug metabolizing enzymes; however, this may be due to statistical reasons only. Thus, further studies with greater CA samples are necessary to draw final conclusions about these genetically based hypotheses. |
SCZ Keywords | schizophrenia,schizophrenic |
2 | Bioorg. Med. Chem. 2013 Oct 21: 6053-62 |
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PMID | 23978358 |
Title | N-Methylanilide and N-methylbenzamide derivatives as phosphodiesterase 10A (PDE10A) inhibitors. |
Abstract | PDE10A is a recently identified phosphodiesterase with a quite remarkable localization since the protein is abundant only in brain tissue. Based on this unique localization, research has focused extensively on using PDE10A modulators as a novel therapeutic approach for dysfunction in the basal ganglia circuit including Parkinson's disease, Huntington's disease, schizophrenia, addiction and obsessive compulsive disorder. Medicinal chemistry efforts identified the N-methyl-N-[4-(quinolin-2-ylmethoxy)-phenyl]-isonicotinamide (8) as a nanomolar PDE10A inhibitor. A subsequent Lead-optimization program identified analogous N-methylanilides and their corresponding N-methylbenzamides (29) as potent PDE10A inhibitors, concurrently some interesting and unexpected binding modes were identified. |
SCZ Keywords | schizophrenia,schizophrenic |
3 | Schizophr Bull 2014 Jul 40: 769-76 |
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PMID | 23734059 |
Title | Methylation patterns in whole blood correlate with symptoms in schizophrenia patients. |
Abstract | DNA methylation, one of the main epigenetic mechanisms to regulate gene expression, appears to be involved in the development of schizophrenia (SZ). In this study, we investigated 7562 DNA methylation markers in blood from 98 SZ patients and 108 healthy controls. A linear regression model including age, gender, race, alcohol, nicotine and cannabis use status, and diagnosis was implemented to identify C-phosphate-G (CpG) sites significantly associated with diagnosis. These CpG sites were further validated using an independent data set. Sixteen CpG sites were identified with hyper- or hypomethylation in patients. A further verification of expression of the corresponding genes identified 7 genes whose expression levels were also significantly altered in patients. While such altered methylation patterns showed no correlation with disorganized symptoms and negative symptoms in patients, 11 CpG sites significantly correlated with reality distortion symptoms. The direction of the correlations indicates that methylation changes possibly play a protective mechanism to lessen delusion and hallucination symptoms in patients. Pathway analyses showed that the most significant biological function of the differentially methylated CpGs is inflammatory response with CD224, LAX1, TXK, PRF1, CD7, MPG, and MPO genes directly involved in activations of T cells, B cells, and natural killer cells or in cytotoxic reaction. Our results suggest that such methylation changes may modulate aspects of the immune response and hence protect against the neurobiological substrate of reality distortion symptoms in SZ patients. |
SCZ Keywords | schizophrenia,schizophrenic |
4 | |
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PMID | 26886746 |
Title | Effects of Electroconvulsive Therapy on Some Inflammatory Factors in Patients With Treatment-Resistant Schizophrenia. |
Abstract | Electroconvulsive therapy (ECT) is the most effective option for several psychiatric conditions, including treatment-resistant schizophrenia. However, little is known about the molecular mechanism of action of ECT. The link between inflammatory system and schizophrenia is the focus of recent studies. However, the impact of ECT on inflammatory functioning in this disorder remains elusive. Whether ECT could modulate inflammatory factors in patients with schizophrenia was examined. Plasma levels of interleukin-4 (IL-4), transforming growth factor-? (TGF-?), myeloperoxidase (MPO), and nuclear factor-?B (NF-?B) activation were analyzed in 20 schizophrenic patients, mainly with resistant to antipsychotic medication disorders, and in 20 sex- and age-matched healthy controls. Disease severity was evaluated using the Brief Psychiatric Rating Scale. All patients were followed with measurement of the inflammatory factors before and after ECT treatment and compared with the controls. Patients with schizophrenia had markedly raised NF-?B and but decreased TGF-? levels compared with healthy controls. On the other hand, no significant differences were found for the levels of IL-4 and MPO levels. The clinical improvement during repeated ECT was accompanied by a gradual and significant increase in IL-4 and TGF-? level, but MPO and NF-?B activation were left unaffected. Increases in TGF-? were negatively correlated with the change in Brief Psychiatric Rating Scale scores after ECT. It is shown that ECT, while increasing the anti-inflammatory response such as the levels of IL-4 and TGF-?, it did not affect the levels of MPO and NF-?B activation in this study. |
SCZ Keywords | schizophrenia,schizophrenic |
5 | |
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PMID | 26886746 |
Title | Effects of Electroconvulsive Therapy on Some Inflammatory Factors in Patients With Treatment-Resistant Schizophrenia. |
Abstract | Electroconvulsive therapy (ECT) is the most effective option for several psychiatric conditions, including treatment-resistant schizophrenia. However, little is known about the molecular mechanism of action of ECT. The link between inflammatory system and schizophrenia is the focus of recent studies. However, the impact of ECT on inflammatory functioning in this disorder remains elusive. Whether ECT could modulate inflammatory factors in patients with schizophrenia was examined. Plasma levels of interleukin-4 (IL-4), transforming growth factor-? (TGF-?), myeloperoxidase (MPO), and nuclear factor-?B (NF-?B) activation were analyzed in 20 schizophrenic patients, mainly with resistant to antipsychotic medication disorders, and in 20 sex- and age-matched healthy controls. Disease severity was evaluated using the Brief Psychiatric Rating Scale. All patients were followed with measurement of the inflammatory factors before and after ECT treatment and compared with the controls. Patients with schizophrenia had markedly raised NF-?B and but decreased TGF-? levels compared with healthy controls. On the other hand, no significant differences were found for the levels of IL-4 and MPO levels. The clinical improvement during repeated ECT was accompanied by a gradual and significant increase in IL-4 and TGF-? level, but MPO and NF-?B activation were left unaffected. Increases in TGF-? were negatively correlated with the change in Brief Psychiatric Rating Scale scores after ECT. It is shown that ECT, while increasing the anti-inflammatory response such as the levels of IL-4 and TGF-?, it did not affect the levels of MPO and NF-?B activation in this study. |
SCZ Keywords | schizophrenia,schizophrenic |