This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Adenylyl Cyclases ; metabolism ; Adrenergic alpha-Antagonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Agmatine ; administration & dosage ; pharmacology ; Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Behavior, Animal ; drug effects ; Depression ; metabolism ; physiopathology ; Dose-Response Relationship, Drug ; Fenclonine ; pharmacology ; Idazoxan ; pharmacology ; Male ; Mice ; Pindolol ; pharmacology ; Random Allocation ; Rats ; Rats, Wistar ; Receptors, Biogenic Amine ; antagonists & inhibitors ; Serotonin 5-HT1 Receptor Antagonists ; Swimming ; Synapses ; enzymology ; Yohimbine ; pharmacology

OBJECTIVETo study the chemical constituents of Excoecaria agallocha L.

METHODThe constituents were isolated and purified by repeated column chromatography and their structures were elucidated by spectroscopic analysis.

RESULTSix triterpenoids including taraxerone (1), beta-amyrin acetate (2), 3beta-[(2E,4E)-6-oxo-decadienoyloxy]-olean-12-ene (3), taraxerol (4), acetylaleuritolic acid (5), and cycloart-22-ene-3beta, 25-diol (6), and three steroids including beta-sitostenone (7), (24R)-24-ethylcholesta-4,22-dien-3-one (8), and beta-sitosterol (9) were isolated and identified from the stems and twigs of the mangrove plant E. agallocha.

CONCLUSIONCompounds 5-8 were isolated from E. agallocha for the first time.

Euphorbiaceae ; chemistry ; Magnetic Resonance Spectroscopy ; Oleanolic Acid ; analogs & derivatives ; chemistry ; isolation & purification ; Sitosterols ; chemistry ; isolation & purification ; Steroids ; chemistry ; isolation & purification ; Triterpenes ; chemistry ; isolation & purification

OBJECTIVETo evaluate the clinical and laboratory features of pediatric inv(16) acute myeloid leukemia (AML) retrospectively.

METHODDual color fluorescence in situ hybridization (D-FISH) using a LSI CBFβ inv(16) break apart probe labeled by Spectrum red and Spectrum green was performed in 15 acute myeloid leukemia cases, including 13 cases with or without abnormal eosinophils but with positive core binding factor β (CBFβ)-MYH11 fusion transcript detected by RT-PCR, and 2 cases with trisomy 8 (+8). The results were compared with the morphology, immunophenotype, karyotype and RT-PCR.

RESULTMorphologically, 12 cases were diagnosed as M(4)EO, 2 as M(4), and 1 as M(2a). Immunophenotypically, all 13 AML cases with inv(16) showed positive expression of CD(13) and CD(33), but without the expression of any lymphoid lineage antigens. Karyotyping analysis with G-banding detected inv(16) in 10 AML cases, including 9 M(4)EO cases and 1 M(2a), but only 5 positive cases were detected using R-banding technique. Among them, 2 cases had simultaneous +8 and trisomy22 (+22), one had +22 only in addition to inv(16). D-FISH revealed a CBFβ-MYH11 rearrangement in 13 cases of AML with positive RT-PCR results, and the mean positive rate of cell detection was 55.15% (range 37.0% - 86.0%). The complete remission rate (CR) and median survival period in this series of inv(16) AML were 81.5%and 11 months, respectively, of whom, 8 cases were still in CR. Relapse and karyotypic evolution were seen in case 5 with +8, +22 in addition to inv(16).

CONCLUSIONAML with inv(16) is a special subtype. Most cases belong to M(4)EO. Its prognosis is good in general, but it seems to be an unfavorable feature for AML with inv(16) and +8, +22 simultaneously, especially with karyotypic evolution. For detection of inv(16), G-banding technique is evidently superior to R-banding technique. D-FISH combined with RT-PCR are more sensitive and reliable than chromosome banding analysis.

Adolescent ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosome Inversion ; Chromosomes, Human, Pair 16 ; genetics ; Eosinophilia ; pathology ; Female ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Infant ; Karyotyping ; Leukemia, Myeloid, Acute ; diagnosis ; genetics ; Male ; Prognosis ; Retrospective Studies ; Reverse Transcriptase Polymerase Chain Reaction

OBJECTIVE: To explore the expression pattern and clinical significance of Integral membrane protein 2A（ITM2A） in drug resistant patients with chronic myeloid leukemia (CML). METHODS: The expression of ITM2A in CML was evaluated by qRT-PCR, Western blot and immunocytochemistry. In order to understand the possible biological effects of ITM2A, apoptosis, cell cycle and myeloid differentiation antigen expression of CML cells were detected by flow cytometry after over-expression of ITM2A. The nuderlying molecular mechanism of its biological effect was explored. RESULTS: The expression of ITM2A in bone marrow of CML resistant patients was significantly lower than that of sensitive patients and healthy donors（P<0.05）. The CML resistant strain cell K562R was successfully constructed in vitro. The expression of ITM2A in the resistant strain was significantly lower than that in the sensitive strain(P<0.05). Overexpression of ITM2A in K562R cells increased the sensitivity of K562R cells to imatinib and blocked the cell cycle in G₂ phase(P<0.05), but did not affect myeloid differentiation. Mechanistically, up-regulation of ITM2A reduced phosphorylation in ERK signaling (P<0.05). CONCLUSION The expression of ITM2A was low in patients with drug resistance of CML, and the low expression of ITM2A may be the key factor of imatinib resistance in CML.
Humans ; Antineoplastic Agents/pharmacology* ; Apoptosis ; Drug Resistance, Neoplasm ; Imatinib Mesylate/therapeutic use* ; K562 Cells ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Signal Transduction