Input: Upregulation of T - cell factor - 4 isoform - responsive target genes in hepatocellular carcinoma . BACKGROUND : The Wnt / beta - catenin signalling pathway regulates genes involved in cell proliferation , survival , migration and invasion through regulation by T - cell factor ( TCF ) - 4 transcription factor proteins . However , the role of TCF - 4 isoforms generated by alternative splicing events in hepatocellular carcinoma ( HCC ) is unknown . AIM : Here , we investigated TCF - 4 isoforms ( TCF - 4J and K ) - responsive target genes that are important in hepatic oncogenesis and tumour development . METHODS : Gene expression microarray was performed on HCC cells overexpressing TCF - 4J and K isoforms . Expression level of selected target genes was evaluated and correlations were made between their expression level and that of TCF - 4 isoform in 47 pairs of human HCC tumours . RESULTS : Comparison by gene expression microarray revealed that 447 genes were upregulated and 343 downregulated more than 2 . 0 - fold in TCF - 4J compared with TCF - 4K expressing cells . We validated expression of 18 selected target genes involved in Wnt / beta - catenin , insulin / IGF - 1 / IRS1 and Notch signalling pathways in 47 pairs of human HCCs and adjacent uninvolved liver tissues . It was observed that 13 genes ( CLDN2 , STK17B , SPP1 , AXIN2 , WISP2 , MMP7 , IRS1 , ANXA1 , CAMK2N1 , ASPH , GPR56 , CD24 and JAG1 ) activated by TCF - 4J isoform in HCC cells , were also upregulated in HCC tumours compared with adjacent peritumour tissue ; more importantly , 10 genes exhibited a significant correlation with the TCF - 4J expression level in tumour . CONCLUSION : TCF - 4 isoforms ( TCF - 4J and K ) activated different downstream target genes in HCC . The biological consequence of TCF - 4J isoform expression was upregulation of genes associated with tripartite Wnt / beta - catenin , insulin / IGF - 1 / IRS1 and Notch signal transduction pathway activation , which contribute to the pathogenesis of HCC .

T - cell factor - 4

Wnt

beta - catenin

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

Wnt

beta - catenin

insulin

IGF - 1

Notch

ASPH

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

Wnt

beta - catenin

insulin

IGF - 1

Notch

hepatocellular carcinoma

hepatocellular carcinoma

HCC

hepatic oncogenesis

tumour

HCC

HCC tumours

HCCs

HCC

HCC tumours

tumour

HCC

HCC

human

human

hepatocellular carcinoma

hepatocellular carcinoma

HCC

hepatic oncogenesis

HCC

HCC tumours

HCCs

HCC

HCC tumours

HCC

HCC

hepatocellular carcinoma

hepatocellular carcinoma

HCC

hepatic oncogenesis

HCC

HCC tumours

HCCs

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HCC

HCC

hepatocellular carcinoma

hepatocellular carcinoma

HCC

hepatic oncogenesis

HCC

HCC tumours

HCCs

HCC

HCC tumours

HCC

HCC

ASPH

hepatocellular carcinoma

ASPH

hepatocellular carcinoma

ASPH

HCC

ASPH

hepatic oncogenesis

ASPH

HCC

ASPH

HCC tumours

ASPH

HCCs

ASPH

HCC

ASPH

HCC tumours

ASPH

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ASPH

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hepatocellular carcinoma

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HCC

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HCC

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HCC tumours

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hepatocellular carcinoma

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HCC

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HCC

HCC tumours

HCCs

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HCC tumours

HCC

HCC

hepatocellular carcinoma

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HCC

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HCC

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hepatocellular carcinoma

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HCC

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hepatocellular carcinoma

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HCC

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T - cell factor - 4

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T - cell factor ( TCF ) - 4 transcription factor

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T - cell factor ( TCF ) - 4 transcription factor

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TCF - 4

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T - cell factor - 4

HCC

T - cell factor - 4

HCC tumours

T - cell factor - 4

HCC

T - cell factor - 4

HCC

T - cell factor ( TCF ) - 4 transcription factor

hepatocellular carcinoma

T - cell factor ( TCF ) - 4 transcription factor

hepatocellular carcinoma

T - cell factor ( TCF ) - 4 transcription factor

HCC

T - cell factor ( TCF ) - 4 transcription factor

hepatic oncogenesis

T - cell factor ( TCF ) - 4 transcription factor

HCC

T - cell factor ( TCF ) - 4 transcription factor

HCC tumours

T - cell factor ( TCF ) - 4 transcription factor

HCCs

T - cell factor ( TCF ) - 4 transcription factor

HCC

T - cell factor ( TCF ) - 4 transcription factor

HCC tumours

T - cell factor ( TCF ) - 4 transcription factor

HCC

T - cell factor ( TCF ) - 4 transcription factor

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

HCC

TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

HCC

TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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HCCs

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TCF - 4J

hepatocellular carcinoma

TCF - 4J

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HCC tumours

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HCC

TCF - 4J

hepatocellular carcinoma

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TCF - 4J

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TCF - 4J

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TCF - 4

hepatocellular carcinoma

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TCF - 4

HCC

TCF - 4

hepatic oncogenesis

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HCC

TCF - 4

HCC tumours

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HCCs

TCF - 4

HCC

TCF - 4

HCC tumours

TCF - 4

HCC

TCF - 4

HCC

TCF - 4J and K

hepatocellular carcinoma

TCF - 4J and K

hepatocellular carcinoma

TCF - 4J and K

HCC

TCF - 4J and K

hepatic oncogenesis

TCF - 4J and K

HCC

TCF - 4J and K

HCC tumours

TCF - 4J and K

HCCs

TCF - 4J and K

HCC

TCF - 4J and K

HCC tumours

TCF - 4J and K

HCC

TCF - 4J and K

HCC

TCF - 4J

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TCF - 4J

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TCF - 4J

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HCC

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HCC

Notch

hepatocellular carcinoma

Notch

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Notch

HCC

Notch

hepatic oncogenesis

Notch

HCC

Notch

HCC tumours

Notch

HCCs

Notch

HCC

Notch

HCC tumours

Notch

HCC

Notch

HCC

Notch

hepatocellular carcinoma

Notch

hepatocellular carcinoma

Notch

HCC

Notch

hepatic oncogenesis

Notch

HCC

Notch

HCC tumours

Notch

HCCs

Notch

HCC

Notch

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Notch

HCC

Notch

HCC

hepatocellular carcinoma

hepatocellular carcinoma

HCC

hepatic oncogenesis

HCC

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HCCs

HCC

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HCC

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hepatocellular carcinoma

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HCC

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HCC

HCC

hepatocellular carcinoma

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HCC

hepatic oncogenesis

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HCC tumours

HCCs

HCC

HCC tumours

HCC

HCC

IGF - 1

IGF - 1

IGF - 1

IGF - 1

IGF - 1

IGF - 1

IGF - 1

hepatocellular carcinoma

IGF - 1

hepatocellular carcinoma

IGF - 1

HCC

IGF - 1

hepatic oncogenesis

IGF - 1

HCC

IGF - 1

HCC tumours

IGF - 1

HCCs

IGF - 1

HCC

IGF - 1

HCC tumours

IGF - 1

HCC

IGF - 1

HCC

IGF - 1

hepatocellular carcinoma

IGF - 1

hepatocellular carcinoma

IGF - 1

HCC

IGF - 1

hepatic oncogenesis

IGF - 1

HCC

IGF - 1

HCC tumours

IGF - 1

HCCs

IGF - 1

HCC

IGF - 1

HCC tumours

IGF - 1

HCC

IGF - 1

HCC

insulin

insulin

insulin

insulin

insulin

insulin

insulin

IGF - 1

insulin

IGF - 1

insulin

IGF - 1

insulin

IGF - 1

insulin

hepatocellular carcinoma

insulin

hepatocellular carcinoma

insulin

HCC

insulin

hepatic oncogenesis

insulin

HCC

insulin

HCC tumours

insulin

HCCs

insulin

HCC

insulin

HCC tumours

insulin

HCC

insulin

HCC

insulin

hepatocellular carcinoma

insulin

hepatocellular carcinoma

insulin

HCC

insulin

hepatic oncogenesis

insulin

HCC

insulin

HCC tumours

insulin

HCCs

insulin

HCC

insulin

HCC tumours

insulin

HCC

insulin

HCC

beta - catenin

hepatocellular carcinoma

beta - catenin

hepatocellular carcinoma

beta - catenin

HCC

beta - catenin

hepatic oncogenesis

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCCs

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCC

beta - catenin

HCC

beta - catenin

hepatocellular carcinoma

beta - catenin

hepatocellular carcinoma

beta - catenin

HCC

beta - catenin

hepatic oncogenesis

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCCs

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCC

beta - catenin

HCC

beta - catenin

hepatocellular carcinoma

beta - catenin

hepatocellular carcinoma

beta - catenin

HCC

beta - catenin

hepatic oncogenesis

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCCs

beta - catenin

HCC

beta - catenin

HCC tumours

beta - catenin

HCC

beta - catenin

HCC

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

beta - catenin

Wnt

hepatocellular carcinoma

Wnt

hepatocellular carcinoma

Wnt

HCC

Wnt

hepatic oncogenesis

Wnt

HCC

Wnt

HCC tumours

Wnt

HCCs

Wnt

HCC

Wnt

HCC tumours

Wnt

HCC

Wnt

HCC

Wnt

hepatocellular carcinoma

Wnt

hepatocellular carcinoma

Wnt

HCC

Wnt

hepatic oncogenesis

Wnt

HCC

Wnt

HCC tumours

Wnt

HCCs

Wnt

HCC

Wnt

HCC tumours

Wnt

HCC

Wnt

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Wnt

hepatocellular carcinoma

Wnt

hepatocellular carcinoma

Wnt

HCC

Wnt

hepatic oncogenesis

Wnt

HCC

Wnt

HCC tumours

Wnt

HCCs

Wnt

HCC

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HCC tumours

Wnt

HCC

Wnt

HCC

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

ASPH

T - cell factor ( TCF ) - 4 transcription factor

ASPH

TCF - 4

ASPH

TCF - 4

ASPH

TCF - 4J and K

ASPH

TCF - 4J and K

ASPH

TCF - 4

ASPH

TCF - 4J

ASPH

TCF - 4K

ASPH

TCF - 4J

ASPH

TCF - 4J

ASPH

TCF - 4

ASPH

TCF - 4J and K

ASPH

TCF - 4J

ASPH

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

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TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4

TCF - 4J

TCF - 4K

TCF - 4J

TCF - 4J

TCF - 4

TCF - 4J and K

TCF - 4J

T - cell factor - 4

Notch

T - cell factor - 4

Notch

T - cell factor ( TCF ) - 4 transcription factor

Notch

T - cell factor ( TCF ) - 4 transcription factor

Notch

TCF - 4

Notch

TCF - 4

Notch

TCF - 4

Notch

TCF - 4

Notch

TCF - 4J and K

Notch

TCF - 4J and K

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TCF - 4J and K

Notch

TCF - 4J and K

Notch

TCF - 4

Notch

TCF - 4

Notch

TCF - 4J

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TCF - 4J

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TCF - 4K

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TCF - 4K

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TCF - 4J

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TCF - 4

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TCF - 4

Notch

TCF - 4J and K

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TCF - 4J and K

Notch

TCF - 4J

Notch

TCF - 4J

Notch

T - cell factor - 4

T - cell factor - 4

T - cell factor - 4

T - cell factor ( TCF ) - 4 transcription factor

T - cell factor ( TCF ) - 4 transcription factor

T - cell factor ( TCF ) - 4 transcription factor

TCF - 4

TCF - 4

TCF - 4

TCF - 4

TCF - 4

TCF - 4

TCF - 4J and K

TCF - 4J and K

TCF - 4J and K

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TCF - 4J and K

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T - cell factor - 4

IGF - 1

T - cell factor - 4

IGF - 1

T - cell factor ( TCF ) - 4 transcription factor

IGF - 1

T - cell factor ( TCF ) - 4 transcription factor

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IGF - 1

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IGF - 1

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IGF - 1

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IGF - 1

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IGF - 1

TCF - 4J

IGF - 1

TCF - 4

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TCF - 4J and K

IGF - 1

TCF - 4J and K

IGF - 1

TCF - 4J

IGF - 1

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IGF - 1

T - cell factor - 4

insulin

T - cell factor - 4

insulin

T - cell factor ( TCF ) - 4 transcription factor

insulin

T - cell factor ( TCF ) - 4 transcription factor

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TCF - 4

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TCF - 4

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TCF - 4

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TCF - 4

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4J and K

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TCF - 4

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TCF - 4

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TCF - 4J

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TCF - 4J

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TCF - 4J

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TCF - 4

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TCF - 4J and K

insulin

TCF - 4J and K

insulin

TCF - 4J

insulin

TCF - 4J

insulin

T - cell factor - 4

beta - catenin

T - cell factor - 4

beta - catenin

T - cell factor - 4

beta - catenin

T - cell factor ( TCF ) - 4 transcription factor

beta - catenin

T - cell factor ( TCF ) - 4 transcription factor

beta - catenin

T - cell factor ( TCF ) - 4 transcription factor

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4K

beta - catenin

TCF - 4K

beta - catenin

TCF - 4K

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J and K

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

TCF - 4J

beta - catenin

T - cell factor - 4

Wnt

T - cell factor - 4

Wnt

T - cell factor - 4

Wnt

T - cell factor ( TCF ) - 4 transcription factor

Wnt

T - cell factor ( TCF ) - 4 transcription factor

Wnt

T - cell factor ( TCF ) - 4 transcription factor

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4K

Wnt

TCF - 4K

Wnt

TCF - 4K

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J and K

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt

TCF - 4J

Wnt


Input: Nicotine antagonizes caffeine - but not pentylenetetrazole - induced anxiogenic effect in mice . RATIONALE : Nicotine and caffeine are widely consumed licit psychoactive drugs worldwide . Epidemiological studies showed that they were generally used concurrently . Although some studies in experimental animals indicate clear pharmacological interactions between them , no studies have shown a specific interaction on anxiety responses . OBJECTIVES : The present study investigates the effects of nicotine on anxiety induced by caffeine and another anxiogenic drug , pentylenetetrazole , in mice . The elevated plus - maze ( EPM ) test was used to evaluate the effects of drugs on anxiety . METHODS : Adult male Swiss Webster mice ( 25 - 32 g ) were given nicotine ( 0 . 05 - 0 . 25 mg / kg s . c . ) or saline 10 min before caffeine ( 70 mg / kg i . p . ) or pentylenetetrazole ( 15 and 30 mg / kg i . p . ) injections . After 15 min , mice were evaluated for their open - and closed - arm time and entries on the EPM for a 10 - min session . Locomotor activity was recorded for individual groups by using the same treatment protocol with the EPM test . RESULTS : Nicotine ( 0 . 05 - 0 . 25 mg / kg ) itself did not produce any significant effect in the EPM test , whereas caffeine ( 70 mg / kg ) and pentylenetetrazole ( 30 mg / kg ) produced an anxiogenic effect , apparent with decreases in open - arm time and entry . Nicotine ( 0 . 25 mg / kg ) pretreatment blocked the caffeine - but not pentylenetetrazole - induced anxiety . Administration of each drug and their combinations did not produce any effect on locomotor activity . CONCLUSIONS : Our results suggest that the antagonistic effect of nicotine on caffeine - induced anxiety is specific to caffeine , instead of a non - specific anxiolytic effect . Thus , it may extend the current findings on the interaction between nicotine and caffeine .

Nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

psychoactive drugs

nicotine

caffeine

anxiogenic drug

pentylenetetrazole

nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

pentylenetetrazole

Nicotine

caffeine

pentylenetetrazole

nicotine

caffeine

caffeine

nicotine

caffeine

anxiogenic effect

anxiety

anxiety

anxiety

anxiogenic effect

anxiety

anxiety

mice

mice

mice

mice

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

pentylenetetrazole

anxiogenic effect

pentylenetetrazole

anxiety

pentylenetetrazole

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

caffeine

anxiety

caffeine

anxiogenic effect

caffeine

anxiety

caffeine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiety

Nicotine

anxiogenic effect

Nicotine

anxiety

Nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

nicotine

anxiety

nicotine

anxiogenic effect

nicotine

anxiety

nicotine

anxiety

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

Nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine

nicotine

caffeine


Input: The influence of the time interval between monoHER and doxorubicin administration on the protection against doxorubicin - induced cardiotoxicity in mice . PURPOSE : Despite its well - known cardiotoxicity , the anthracyclin doxorubicin ( DOX ) continues to be an effective and widely used chemotherapeutic agent . DOX - induced cardiac damage presumably results from the formation of free radicals by DOX . Reactive oxygen species particularly affect the cardiac myocytes because these cells seem to have a relatively poor antioxidant defense system . The semisynthetic flavonoid monohydroxyethylrutoside ( monoHER ) showed cardioprotection against DOX - induced cardiotoxicity through its radical scavenging and iron chelating properties . Because of the relatively short final half - life of monoHER ( about 30 min ) , it is expected that the time interval between monoHER and DOX might be of influence on the cardioprotective effect of monoHER . Therefore , the aim of the present study was to investigate this possible effect . METHODS : Six groups of 6 BALB / c mice were treated with saline , DOX alone or DOX ( 4 mg / kg i . v . ) preceded by monoHER ( 500 mg / kg i . p . ) with an interval of 10 , 30 , 60 or 120 min . After a 6 - week treatment period and additional observation for 2 weeks , the mice were sacrificed . Their cardiac tissues were processed for light microscopy , after which cardiomyocyte damage was evaluated according to Billingham ( in Cancer Treat Rep 62 ( 6 ) : 865 - 872 , 1978 ) . Microscopic evaluation revealed that treatment with DOX alone induced significant cardiac damage in comparison to the saline control group ( P < 0 . 001 ) . RESULTS : The number of damaged cardiomyocytes was 9 . 6 - fold ( 95 % CI 4 . 4 - 21 . 0 ) higher in mice treated with DOX alone than that in animals of the control group . The ratio of aberrant cardiomyocytes in mice treated with DOX preceded by monoHER and those in mice treated with saline ranged from 1 . 6 to 2 . 8 ( mean 2 . 2 , 95 % CI 1 . 2 - 4 . 1 , P = 0 . 019 ) . The mean protective effect by adding monoHER before DOX led to a significant 4 . 4 - fold reduction ( P < 0 . 001 , 95 % CI 2 . 3 - 8 . 2 ) of abnormal cardiomyocytes . This protective effect did not depend on the time interval between monoHER and DOX administration ( P = 0 . 345 ) . CONCLUSION : The results indicate that in an outpatient clinical setting monoHER may be administered shortly before DOX .

monoHER

doxorubicin

doxorubicin

anthracyclin

doxorubicin

DOX

DOX

DOX

oxygen

flavonoid

monohydroxyethylrutoside

monoHER

DOX

iron

monoHER

monoHER

DOX

monoHER

DOX

DOX

monoHER

DOX

DOX

DOX

monoHER

monoHER

DOX

monoHER

DOX

monoHER

DOX

cardiotoxicity

cardiotoxicity

cardiac damage

cardiotoxicity

cardiomyocyte damage

cardiac damage

mice

mice

mice

mice

mice

mice

outpatient

iron

cardiotoxicity

iron

cardiotoxicity

iron

cardiotoxicity

iron

doxorubicin

iron

doxorubicin

iron

doxorubicin

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

iron

DOX

monoHER

iron

monohydroxyethylrutoside

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

iron

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monohydroxyethylrutoside

cardiotoxicity

monohydroxyethylrutoside

cardiotoxicity

monohydroxyethylrutoside

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

cardiotoxicity

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monohydroxyethylrutoside

doxorubicin

monohydroxyethylrutoside

doxorubicin

monohydroxyethylrutoside

doxorubicin

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monohydroxyethylrutoside

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

doxorubicin

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

monoHER

DOX

flavonoid

cardiotoxicity

flavonoid

cardiotoxicity

flavonoid

cardiotoxicity

flavonoid

doxorubicin

flavonoid

doxorubicin

flavonoid

doxorubicin

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

flavonoid

DOX

doxorubicin

cardiac damage

doxorubicin

cardiac damage

doxorubicin

cardiac damage

doxorubicin

cardiac damage

doxorubicin

cardiac damage

doxorubicin

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

DOX

cardiac damage

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

doxorubicin

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity

DOX

cardiotoxicity


Input: Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl . OBJECTIVE : In vitro work has demonstrated that cinacalcet is a strong inhibitor of cytochrome P450 isoenzyme ( CYP ) 2D6 . The purpose of this study was to evaluate the effect of cinacalcet on CYP2D6 activity , using desipramine as a probe substrate , in healthy subjects . METHODS : Seventeen subjects who were genotyped as CYP2D6 extensive metabolizers were enrolled in this randomized , open - label , crossover study to receive a single oral dose of desipramine ( 50 mg ) on two separate occasions , once alone and once after multiple doses of cinacalcet ( 90 mg for 7 days ) . Blood samples were obtained predose and up to 72 h postdose . RESULTS : Fourteen subjects completed both treatment arms . Relative to desipramine alone , mean AUC and C ( max ) of desipramine increased 3 . 6 - and 1 . 8 - fold when coadministered with cinacalcet . The t ( 1 / 2 , z ) of desipramine was longer when desipramine was coadministered with cinacalcet ( 21 . 0 versus 43 . 3 hs ) . The t ( max ) was similar between the regimens . Fewer subjects reported adverse events following treatment with desipramine alone than when receiving desipramine with cinacalcet ( 33 versus 86 % ) , the most frequent of which ( nausea and headache ) have been reported for patients treated with either desipramine or cinacalcet . CONCLUSION : This study demonstrates that cinacalcet is a strong inhibitor of CYP2D6 . These data suggest that during concomitant treatment with cinacalcet , dose adjustment may be necessary for drugs that demonstrate a narrow therapeutic index and are metabolized by CYP2D6 .

desipramine HCl

cinacalcet HCl

cinacalcet

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

desipramine

cinacalcet

desipramine

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

nausea

headache

patients

cinacalcet HCl

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet

headache

cinacalcet HCl

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

cinacalcet

nausea

desipramine HCl

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine

headache

desipramine HCl

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

desipramine

nausea

cinacalcet HCl

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet HCl

cinacalcet HCl

cinacalcet HCl

cinacalcet HCl

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cinacalcet

cytochrome P450 isoenzyme ( CYP ) 2D6

cinacalcet

cinacalcet

cinacalcet

cinacalcet

desipramine HCl

cinacalcet HCl

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine HCl

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet HCl

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet

desipramine

cinacalcet


Input: Antipsychotic - like profile of thioperamide , a selective H3 - receptor antagonist in mice . Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia . The present study was designed to study the effect of histamine H ( 3 ) - receptor ligands on neuroleptic - induced catalepsy , apomorphine - induced climbing behavior and amphetamine - induced locomotor activities in mice . Catalepsy was induced by haloperidol ( 2 mg / kg p . o . ) , while apomorphine ( 1 . 5 mg / kg s . c . ) and amphetamine ( 2 mg / kg s . c . ) were used for studying climbing behavior and locomotor activities , respectively . ( R ) - alpha - methylhistamine ( RAMH ) ( 5 microg i . c . v . ) and thioperamide ( THP ) ( 15 mg / kg i . p . ) , per se did not cause catalepsy . Administration of THP ( 3 . 75 , 7 . 5 and 15 mg / kg i . p . ) 1 h prior to haloperidol resulted in a dose - dependent increase in the catalepsy times ( P < 0 . 05 ) . However , pretreatment with RAMH significantly reversed such an effect of THP ( 15 mg / kg i . p . ) . RAMH per se showed significant reduction in locomotor time , distance traveled and average speed but THP ( 15 mg / kg i . p . ) per se had no effect on these parameters . On amphetamine - induced hyperactivity , THP ( 3 . 75 and 7 . 5 mg / kg i . p . ) reduced locomotor time , distance traveled and average speed ( P < 0 . 05 ) . Pretreatment with RAMH ( 5 microg i . c . v . ) could partially reverse such effects of THP ( 3 . 75 mg / kg i . p . ) . Climbing behavior induced by apomorphine was reduced in animals treated with THP . Such an effect was , however , reversed in presence of RAMH . THP exhibited an antipsychotic - like profile by potentiating haloperidol - induced catalepsy , reducing amphetamine - induced hyperactivity and reducing apomorphine - induced climbing in mice . Such effects of THP were reversed by RAMH indicating the involvement of histamine H ( 3 ) - receptors . Findings suggest a potential for H ( 3 ) - receptor antagonists in improving the refractory cases of schizophrenia .

Antipsychotic

thioperamide

neuroleptic

apomorphine

amphetamine

haloperidol

apomorphine

amphetamine

( R ) - alpha - methylhistamine

RAMH

thioperamide

THP

THP

haloperidol

RAMH

THP

RAMH

THP

amphetamine

THP

RAMH

THP

apomorphine

THP

RAMH

THP

antipsychotic

haloperidol

amphetamine

apomorphine

THP

RAMH

H ( 3 ) - receptor antagonists

H3 - receptor

histamine H ( 3 ) - receptor

histamine H ( 3 ) - receptors

mice

mice

mice

schizophrenia

catalepsy

Catalepsy

catalepsy

catalepsy

hyperactivity

catalepsy

hyperactivity

schizophrenia

H ( 3 ) - receptor antagonists

schizophrenia

H ( 3 ) - receptor antagonists

schizophrenia

( R ) - alpha - methylhistamine

thioperamide

( R ) - alpha - methylhistamine

thioperamide

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

( R ) - alpha - methylhistamine

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

thioperamide

RAMH

thioperamide

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

RAMH

THP

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

thioperamide

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

THP

apomorphine

thioperamide

hyperactivity

thioperamide

hyperactivity

thioperamide

hyperactivity

thioperamide

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

THP

hyperactivity

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

thioperamide

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

THP

amphetamine

H3 - receptor

thioperamide

H3 - receptor

thioperamide

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

H3 - receptor

THP

histamine H ( 3 ) - receptor

thioperamide

histamine H ( 3 ) - receptor

thioperamide

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptor

THP

histamine H ( 3 ) - receptors

thioperamide

histamine H ( 3 ) - receptors

thioperamide

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

histamine H ( 3 ) - receptors

THP

Antipsychotic

catalepsy

Antipsychotic

Catalepsy

Antipsychotic

catalepsy

Antipsychotic

catalepsy

Antipsychotic

catalepsy

neuroleptic

catalepsy

neuroleptic

Catalepsy

neuroleptic

catalepsy

neuroleptic

catalepsy

neuroleptic

catalepsy

antipsychotic

catalepsy

antipsychotic

Catalepsy

antipsychotic

catalepsy

antipsychotic

catalepsy

antipsychotic

catalepsy

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

Catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

haloperidol

catalepsy

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

amphetamine

hyperactivity

thioperamide

catalepsy

thioperamide

Catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

Catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

thioperamide

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

THP

Catalepsy

THP

catalepsy

THP

catalepsy

THP

catalepsy

thioperamide

haloperidol

thioperamide

haloperidol

thioperamide

haloperidol

thioperamide

haloperidol

thioperamide

haloperidol

thioperamide

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

THP

haloperidol

( R ) - alpha - methylhistamine

H3 - receptor

( R ) - alpha - methylhistamine

histamine H ( 3 ) - receptor

( R ) - alpha - methylhistamine

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors

RAMH

H3 - receptor

RAMH

histamine H ( 3 ) - receptor

RAMH

histamine H ( 3 ) - receptors


Input: Placebo - level incidence of extrapyramidal symptoms ( EPS ) with quetiapine in controlled studies of patients with bipolar mania . OBJECTIVES : To evaluate extrapyramidal symptoms ( EPS ) , including akathisia , with quetiapine in patients with bipolar mania . METHODS : Data were analyzed from four similarly designed , randomized , double - blind , 3 - to 12 - week studies . Two studies evaluated quetiapine monotherapy ( up to 800 mg / day ) ( n = 209 ) versus placebo ( n = 198 ) , with lithium or haloperidol monotherapy as respective active controls . Two studies evaluated quetiapine ( up to 800 mg / day ) in combination with a mood stabilizer ( lithium or divalproex , QTP + Li / DVP ) ( n = 196 ) compared to placebo and mood stabilizer ( PBO + Li / DVP ) ( n = 203 ) . Extrapyramidal symptoms were evaluated using the Simpson - Angus Scale ( SAS ) , the Barnes Akathisia Rating Scale ( BARS ) , adverse event reports and anticholinergic drug usage . RESULTS : The incidence of EPS - related adverse events , including akathisia , was no different with quetiapine monotherapy ( 12 . 9 % ) than with placebo ( 13 . 1 % ) . Similarly , EPS - related adverse events with QTP + Li / DVP ( 21 . 4 % ) were no different than with PBO + Li / DVP ( 19 . 2 % ) . Adverse events related to EPS occurred in 59 . 6 % of patients treated with haloperidol ( n = 99 ) monotherapy , whereas 26 . 5 % of patients treated with lithium ( n = 98 ) monotherapy experienced adverse events related to EPS . The incidence of akathisia was low and similar with quetiapine monotherapy ( 3 . 3 % ) and placebo ( 6 . 1 % ) , and with QTP + Li / DVP ( 3 . 6 % ) and PBO + Li / DVP ( 4 . 9 % ) . Lithium was associated with a significantly higher incidence ( p < 0 . 05 ) of tremor ( 18 . 4 % ) than quetiapine ( 5 . 6 % ) ; cerebellar tremor , which is a known adverse effect of lithium , may have contributed to the elevated rate of tremor in patients receiving lithium therapy . Haloperidol induced a significantly higher incidence ( p < 0 . 001 ) of akathisia ( 33 . 3 % versus 5 . 9 % ) , tremor ( 30 . 3 % versus 7 . 8 % ) , and extrapyramidal syndrome ( 35 . 4 % versus 5 . 9 % ) than quetiapine . No significant differences were observed between quetiapine and placebo on SAS and BARS scores . Anticholinergic use was low and similar with quetiapine or placebo . CONCLUSIONS : In bipolar mania , the incidence of EPS , including akathisia , with quetiapine therapy is similar to that with placebo .

extrapyramidal symptoms

EPS

bipolar mania

extrapyramidal symptoms

EPS

akathisia

bipolar mania

Extrapyramidal symptoms

EPS

akathisia

EPS

EPS

EPS

akathisia

tremor

tremor

tremor

akathisia

tremor

extrapyramidal syndrome

bipolar mania

EPS

akathisia

quetiapine

quetiapine

quetiapine

lithium

haloperidol

quetiapine

lithium

divalproex

QTP

Li

DVP

Li

DVP

anticholinergic drug

quetiapine

QTP

Li

DVP

Li

DVP

haloperidol

lithium

quetiapine

QTP

Li

DVP

Li

DVP

Lithium

quetiapine

lithium

lithium

Haloperidol

quetiapine

quetiapine

Anticholinergic

quetiapine

quetiapine

patients

patients

patients

patients

patients

tremor

lithium

tremor

lithium

tremor

Li

tremor

Li

tremor

Li

tremor

Li

tremor

lithium

tremor

Li

tremor

Li

tremor

Lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

Li

tremor

Li

tremor

Li

tremor

Li

tremor

lithium

tremor

Li

tremor

Li

tremor

Lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

Li

tremor

Li

tremor

Li

tremor

Li

tremor

lithium

tremor

Li

tremor

Li

tremor

Lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

lithium

tremor

Li

tremor

Li

tremor

Li

tremor

Li

tremor

lithium

tremor

Li

tremor

Li

tremor

Lithium

tremor

lithium

tremor

lithium

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

haloperidol

akathisia

Haloperidol

akathisia

Haloperidol

akathisia

Haloperidol

akathisia

Haloperidol

akathisia

Haloperidol

akathisia

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

haloperidol

tremor

Haloperidol

tremor

Haloperidol

tremor

Haloperidol

tremor

Haloperidol

tremor

extrapyramidal symptoms

lithium

extrapyramidal symptoms

lithium

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

lithium

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Lithium

extrapyramidal symptoms

lithium

extrapyramidal symptoms

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

extrapyramidal symptoms

lithium

extrapyramidal symptoms

lithium

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

lithium

extrapyramidal symptoms

Li

extrapyramidal symptoms

Li

extrapyramidal symptoms

Lithium

extrapyramidal symptoms

lithium

extrapyramidal symptoms

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

Extrapyramidal symptoms

lithium

Extrapyramidal symptoms

lithium

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

lithium

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

Li

Extrapyramidal symptoms

Lithium

Extrapyramidal symptoms

lithium

Extrapyramidal symptoms

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

extrapyramidal syndrome

lithium

extrapyramidal syndrome

lithium

extrapyramidal syndrome

Li

extrapyramidal syndrome

Li

extrapyramidal syndrome

Li

extrapyramidal syndrome

Li

extrapyramidal syndrome

lithium

extrapyramidal syndrome

Li

extrapyramidal syndrome

Li

extrapyramidal syndrome

Lithium

extrapyramidal syndrome

lithium

extrapyramidal syndrome

lithium

EPS

lithium

EPS

lithium

EPS

Li

EPS

Li

EPS

Li

EPS

Li

EPS

lithium

EPS

Li

EPS

Li

EPS

Lithium

EPS

lithium

EPS

lithium

extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

haloperidol

extrapyramidal symptoms

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

Extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

haloperidol

Extrapyramidal symptoms

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol

extrapyramidal syndrome

haloperidol

extrapyramidal syndrome

haloperidol

extrapyramidal syndrome

Haloperidol

EPS

haloperidol

EPS

haloperidol

EPS

Haloperidol


Input: Randomized comparison of olanzapine versus risperidone for the treatment of first - episode schizophrenia : 4 - month outcomes . OBJECTIVE : The authors compared 4 - month treatment outcomes for olanzapine versus risperidone in patients with first - episode schizophrenia spectrum disorders . METHOD : One hundred twelve subjects ( 70 % male ; mean age = 23 . 3 years [ SD = 5 . 1 ] ) with first - episode schizophrenia ( 75 % ) , schizophreniform disorder ( 17 % ) , or schizoaffective disorder ( 8 % ) were randomly assigned to treatment with olanzapine ( 2 . 5 - 20 mg / day ) or risperidone ( 1 - 6 mg / day ) . RESULTS : Response rates did not significantly differ between olanzapine ( 43 . 7 % , 95 % CI = 28 . 8 % - 58 . 6 % ) and risperidone ( 54 . 3 % , 95 % CI = 39 . 9 % - 68 . 7 % ) . Among those responding to treatment , more subjects in the olanzapine group ( 40 . 9 % , 95 % CI = 16 . 8 % - 65 . 0 % ) than in the risperidone group ( 18 . 9 % , 95 % CI = 0 % - 39 . 2 % ) had subsequent ratings not meeting response criteria . Negative symptom outcomes and measures of parkinsonism and akathisia did not differ between medications . Extrapyramidal symptom severity scores were 1 . 4 ( 95 % CI = 1 . 2 - 1 . 6 ) with risperidone and 1 . 2 ( 95 % CI = 1 . 0 - 1 . 4 ) with olanzapine . Significantly more weight gain occurred with olanzapine than with risperidone : the increase in weight at 4 months relative to baseline weight was 17 . 3 % ( 95 % CI = 14 . 2 % - 20 . 5 % ) with olanzapine and 11 . 3 % ( 95 % CI = 8 . 4 % - 14 . 3 % ) with risperidone . Body mass index at baseline and at 4 months was 24 . 3 ( 95 % CI = 22 . 8 - 25 . 7 ) versus 28 . 2 ( 95 % CI = 26 . 7 - 29 . 7 ) with olanzapine and 23 . 9 ( 95 % CI = 22 . 5 - 25 . 3 ) versus 26 . 7 ( 95 % CI = 25 . 2 - 28 . 2 ) with risperidone . CONCLUSIONS : Clinical outcomes with risperidone were equal to those with olanzapine , and response may be more stable . Olanzapine may have an advantage for motor side effects . Both medications caused substantial rapid weight gain , but weight gain was greater with olanzapine .

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

risperidone

olanzapine

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

risperidone

olanzapine

Olanzapine

olanzapine

schizophrenia

schizophrenia

schizophrenia

schizophreniform disorder

schizoaffective disorder

parkinsonism

akathisia

Extrapyramidal symptom

weight gain

weight gain

weight gain

patients

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

olanzapine

weight gain

Olanzapine

weight gain

olanzapine

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

risperidone

weight gain

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

risperidone

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

olanzapine

Extrapyramidal symptom

Olanzapine

Extrapyramidal symptom

olanzapine

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizophreniform disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizoaffective disorder

risperidone

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

olanzapine

schizophreniform disorder

Olanzapine

schizophreniform disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

olanzapine

schizoaffective disorder

Olanzapine

schizoaffective disorder

olanzapine

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

risperidone

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

Olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

Olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

olanzapine

schizophrenia

Olanzapine

schizophrenia

olanzapine

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

Olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone

olanzapine

risperidone


Input: Risks and benefits of COX - 2 inhibitors vs non - selective NSAIDs : does their cardiovascular risk exceed their gastrointestinal benefit ? A retrospective cohort study . OBJECTIVES : The risk of acute myocardial infarction ( AMI ) with COX - 2 inhibitors may offset their gastrointestinal ( GI ) benefit compared with non - selective ( NS ) non - steroidal anti - inflammatory drugs ( NSAIDs ) . We aimed to compare the risks of hospitalization for AMI and GI bleeding among elderly patients using COX - 2 inhibitors , NS - NSAIDs and acetaminophen . METHODS : We conducted a retrospective cohort study using administrative data of patients > or = 65 years of age who filled a prescription for NSAID or acetaminophen during 1999 - 2002 . Outcomes were compared using Cox regression models with time - dependent exposures . RESULTS : Person - years of exposure among non - users of aspirin were : 75 , 761 to acetaminophen , 42 , 671 to rofecoxib 65 , 860 to celecoxib , and 37 , 495 to NS - NSAIDs . Among users of aspirin , they were : 14 , 671 to rofecoxib , 22 , 875 to celecoxib , 9 , 832 to NS - NSAIDs and 38 , 048 to acetaminophen . Among non - users of aspirin , the adjusted hazard ratios ( 95 % confidence interval ) of hospitalization for AMI / GI vs the acetaminophen ( with no aspirin ) group were : rofecoxib 1 . 27 ( 1 . 13 , 1 . 42 ) , celecoxib 0 . 93 ( 0 . 83 , 1 . 03 ) , naproxen 1 . 59 ( 1 . 31 , 1 . 93 ) , diclofenac 1 . 17 ( 0 . 99 , 1 . 38 ) and ibuprofen 1 . 05 ( 0 . 74 , 1 . 51 ) . Among users of aspirin , they were : rofecoxib 1 . 73 ( 1 . 52 , 1 . 98 ) , celecoxib 1 . 34 ( 1 . 19 , 1 . 52 ) , ibuprofen 1 . 51 ( 0 . 95 , 2 . 41 ) , diclofenac 1 . 69 ( 1 . 35 , 2 . 10 ) , naproxen 1 . 35 ( 0 . 97 , 1 . 88 ) and acetaminophen 1 . 29 ( 1 . 17 , 1 . 42 ) . CONCLUSION : Among non - users of aspirin , naproxen seemed to carry the highest risk for AMI / GI bleeding . The AMI / GI toxicity of celecoxib was similar to that of acetaminophen and seemed to be better than those of rofecoxib and NS - NSAIDs . Among users of aspirin , both celecoxib and naproxen seemed to be the least toxic .

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

non - steroidal anti - inflammatory drugs

NSAIDs

COX - 2 inhibitors

NSAIDs

acetaminophen

NSAID

acetaminophen

aspirin

acetaminophen

rofecoxib

celecoxib

NSAIDs

aspirin

rofecoxib

celecoxib

NSAIDs

acetaminophen

aspirin

acetaminophen

aspirin

rofecoxib

celecoxib

naproxen

diclofenac

ibuprofen

aspirin

rofecoxib

celecoxib

ibuprofen

diclofenac

naproxen

acetaminophen

aspirin

naproxen

celecoxib

acetaminophen

rofecoxib

NSAIDs

aspirin

celecoxib

naproxen

acute myocardial infarction

AMI

AMI

GI bleeding

AMI

AMI

GI bleeding

AMI

GI toxicity

patients

patients

GI toxicity

celecoxib

GI toxicity

celecoxib

GI toxicity

celecoxib

GI toxicity

celecoxib

GI toxicity

celecoxib

GI toxicity

celecoxib

GI toxicity

rofecoxib

GI toxicity

rofecoxib

GI toxicity

rofecoxib

GI toxicity

rofecoxib

GI toxicity

rofecoxib

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

acetaminophen

GI toxicity

NSAIDs

GI toxicity

non - steroidal anti - inflammatory drugs

GI toxicity

NSAIDs

GI toxicity

NSAIDs

GI toxicity

NSAID

GI toxicity

NSAIDs

GI toxicity

NSAIDs

GI toxicity

NSAIDs

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

GI bleeding

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

acute myocardial infarction

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

celecoxib

AMI

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

GI bleeding

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

acute myocardial infarction

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

rofecoxib

AMI

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

GI bleeding

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

acute myocardial infarction

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

acetaminophen

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

non - steroidal anti - inflammatory drugs

acute myocardial infarction

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

non - steroidal anti - inflammatory drugs

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAID

acute myocardial infarction

NSAID

AMI

NSAID

AMI

NSAID

AMI

NSAID

AMI

NSAID

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

acute myocardial infarction

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

NSAIDs

AMI

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

GI bleeding

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

acute myocardial infarction

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

naproxen

AMI

acute myocardial infarction

COX - 2 inhibitors

acute myocardial infarction

COX - 2 inhibitors

acute myocardial infarction

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

AMI

COX - 2 inhibitors

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

celecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

rofecoxib

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

acetaminophen

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

non - steroidal anti - inflammatory drugs

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAID

aspirin

NSAIDs

aspirin

NSAIDs

aspirin

NSAIDs

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

non - steroidal anti - inflammatory drugs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAID

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

NSAIDs

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

acetaminophen

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

non - steroidal anti - inflammatory drugs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAID

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

non - steroidal anti - inflammatory drugs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAID

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

non - steroidal anti - inflammatory drugs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAID

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs

COX - 2 inhibitors

NSAIDs


Input: Quinine - induced arrhythmia in a patient with severe malaria . It was reported that there was a case of severe malaria patient with jaundice who presented with arrhythmia ( premature ventricular contraction ) while getting quinine infusion was reported . A man , 25 years old , was admitted to hospital with high fever , chill , vomiting , jaundice . The patient was fully conscious , blood pressure 120 / 80 mmHg , pulse rate 100 x / minute , regular . On admission , laboratory examination showed Plasmodium falciparum ( + + + + ) , total bilirubin 8 . 25 mg / dL , conjugated bilirubin 4 . 36 mg / dL , unconjugated bilirubin 3 . 89 mg / dL , potassium 3 . 52 meq / L Patient was diagnosed as severe malaria with jaundice and got quinine infusion in dextrose 5 % 500 mg / 8 hour . On the second day the patient had vomitus , diarrhea , tinnitus , loss of hearing . After 30 hours of quinine infusion the patient felt palpitation and electrocardiography ( ECG ) recording showed premature ventricular contraction ( PVC ) > 5 x / minute , trigemini , constant type - - sinoatrial block , positive U wave . He was treated with lidocaine 50 mg intravenously followed by infusion 1500 mg in dextrose 5 % / 24 hour and potassium aspartate tablet . Quinine infusion was discontinued and changed with sulfate quinine tablets . Three hours later the patient felt better , the frequency of PVC reduced to 4 - 5 x / minute and on the third day ECG was normal , potassium level was 3 . 34 meq / L . He was discharged on 7th day in good condition . Quinine , like quinidine , is a chincona alkaloid that has anti - arrhythmic property , although it also pro - arrhythmic that can cause various arrhythmias , including severe arrhythmia such as multiple PVC . Administration of parenteral quinine must be done carefully and with good observation because of its pro - arrhythmic effect , especially in older patients who have heart diseases or patients with electrolyte disorder ( hypokalemia ) which frequently occurs due to vomiting and or diarrhea in malaria cases .

Quinine

quinine

bilirubin

bilirubin

bilirubin

potassium

quinine

dextrose

quinine

lidocaine

dextrose

potassium aspartate

Quinine

quinine

potassium

Quinine

quinidine

chincona alkaloid

quinine

arrhythmia

severe malaria

severe malaria

jaundice

arrhythmia

premature ventricular contraction

fever

chill

vomiting

jaundice

severe malaria

jaundice

vomitus

diarrhea

tinnitus

loss of hearing

palpitation

premature ventricular contraction

PVC

sinoatrial block

PVC

arrhythmic

arrhythmic

arrhythmias

arrhythmia

PVC

arrhythmic

heart diseases

electrolyte disorder

hypokalemia

vomiting

diarrhea

malaria

patient

patient

man

patient

Plasmodium falciparum

Patient

patient

patient

patient

patients

patients

premature ventricular contraction

potassium aspartate

premature ventricular contraction

potassium aspartate

PVC

potassium aspartate

PVC

potassium aspartate

PVC

potassium aspartate

premature ventricular contraction

lidocaine

premature ventricular contraction

lidocaine

PVC

lidocaine

PVC

lidocaine

PVC

lidocaine

jaundice

Quinine

jaundice

quinine

jaundice

quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

jaundice

Quinine

jaundice

quinine

Quinine

severe malaria

Quinine

severe malaria

Quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

Quinine

severe malaria

Quinine

severe malaria

Quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

Quinine

severe malaria

Quinine

severe malaria

Quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

quinine

severe malaria

Quinine

sinoatrial block

quinine

sinoatrial block

quinine

sinoatrial block

quinine

sinoatrial block

Quinine

sinoatrial block

quinine

sinoatrial block

Quinine

sinoatrial block

quinine

sinoatrial block

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

Quinine

premature ventricular contraction

Quinine

premature ventricular contraction

Quinine

PVC

Quinine

PVC

Quinine

PVC

quinine

premature ventricular contraction

quinine

premature ventricular contraction

quinine

PVC

quinine

PVC

quinine

PVC

Quinine

palpitation

Quinine

heart diseases

quinine

palpitation

quinine

heart diseases

quinine

palpitation

quinine

heart diseases

quinine

palpitation

quinine

heart diseases

Quinine

palpitation

Quinine

heart diseases

quinine

palpitation

quinine

heart diseases

Quinine

palpitation

Quinine

heart diseases

quinine

palpitation

quinine

heart diseases

Quinine

arrhythmia

Quinine

arrhythmia

Quinine

arrhythmic

Quinine

arrhythmic

Quinine

arrhythmias

Quinine

arrhythmia

Quinine

arrhythmic

quinine

arrhythmia

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmic

quinine

arrhythmias

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmia

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmic

quinine

arrhythmias

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmia

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmic

quinine

arrhythmias

quinine

arrhythmia

quinine

arrhythmic

Quinine

arrhythmia

Quinine

arrhythmia

Quinine

arrhythmic

Quinine

arrhythmic

Quinine

arrhythmias

Quinine

arrhythmia

Quinine

arrhythmic

quinine

arrhythmia

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmic

quinine

arrhythmias

quinine

arrhythmia

quinine

arrhythmic

Quinine

arrhythmia

Quinine

arrhythmia

Quinine

arrhythmic

Quinine

arrhythmic

Quinine

arrhythmias

Quinine

arrhythmia

Quinine

arrhythmic

quinine

arrhythmia

quinine

arrhythmia

quinine

arrhythmic

quinine

arrhythmic

quinine

arrhythmias

quinine

arrhythmia

quinine

arrhythmic