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OBJECTIVE AMPK activator,act as exer-cise mimetics,effective in preventing or ameliorating met-abolic diseases,including obesity and diabetes.Systemic activating of AMPK represents an important therapeutic strategy to treat metabolic diseases.However,whether far-infrared(FIR)hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regu-lation,and its underling mechanisms remain unclear.METHODS The mice were subjected to hyperthermia in the FIR chamber(30±1)℃for 14 d.Exercise endurance was determined using a treadmill.Blood flow were mea-sured by the laser speckle contrast imaging.Combina-tion of microbiomic and metabolomic analysis,diversity of microbiota and metabolic profiling in muscle were detected.The microbiota disorder model via treatment with different cocktails of antibiotics(ABX).RESULTS The material characterization shows that the graphene synthesized by chemical vapour deposition(CVD)is dif-ferent from carbon fi ber,with single-layer structure and high electrothermal transform efficiency.The emission spectra generated by graphene-FIR device would maxi-mize matching those adsorbed by tissues(≈8.0 μm).Gra-phene-FIR improves core and epidermal temperature,and increases blood flow in femoral muscle and abdo-men.The diversity of gut microbiota was increased by graphene-FIR exposure.Graphene-FIR reduced the bac-teroidetes/firmicutes(B/F)ratio and increased the abun-dance of short-chain fatty acids(SCFA)-producing bac-teria,including Allobaculum,Blautia and Anaerostipes.Additionally,graphene-FIR stimulated the expression of SCFAs-sensing receptor(GPR 43),p-AMPK Thr172 and GLUT4,and increased the AMP/ATP ratio,thus enhanc-ing muscle glucose uptake.Metabolomic analyses revealed the significant changes in 25 metabolites,with twenty increased(eg.creatinine and phosphate)and five decreased(eg.lactic acid),and the marked impact of five metabolic pathways,including galactose metabo-lism,glycolysis,gluconeogenesis,fatty acid biosynthesis,butanoate metabolism,pyruvate metabolism.Further-more,a microbiota disorder model also demonstrates that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4.CON-CLUSION Our results provide convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis.These novel insights into graphene-FIR therapy suggest a potential as an exercise mimetic for the treatment of metabolic disease in clinical.
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OBJECTIVE Insomnia is the most fre-quent sleep disorder worldwide and the clinical applica-tion of therapeutic drugs has various adverse effects.In recent years,drugs developed from natural herbs have become potential alternative therapies for insomnia.Nuciferine,one of the main bioactive components obtained from the lotus leaves,has been reported to possess extensive pharmacological activities.However,its hypnotic and sleep regulatory effects have rarely been reported.Hence,this study was intended to investigate the pharma-cological effects of nuciferine and its mechanisms of action in insomnia.METHODS The hypnotic and seda-tive effects of nuciferine were investigated using the eval-uation of locomotor activity test and pentobarbital-induced sleep test in normal and serotonin(5-HT)depletion-induced insomniac mice.Furthermore,the sleep regulatory effects,including sleep time,sleep architecture,and δ-wave power spectral density,were explored using elec-troencephalography/electromyogram(EEG/EMG)-based sleep profiling in normal rats.Finally,the mechanisms of the hypnotic and sedative effects of nuciferine were explored usingin vivoand in silico experiments.RESULTS Nuciferine reduced locomotor activity and prolonged pen-tobarbital-induced sleep time in a dose-dependent man-ner in normal and insomniac model mice.Nuciferine sig-nificantly increased the total sleep time and non-rapid eye movement(NREM)sleep time,inhibited NREM sleep fragmentation,and improved delta power between 0.5 Hz and 1 Hz in normal rats.The results of molecular experiments showed that nuciferine could increase the 5-HT content and 5-HT1A receptor level in the hypothala-mus of insomnia model mice.CONCLUSION This study combined network pharmacological prediction and experi-mental pharmacological techniques to discover the seda-tive-hypnotic effect of nuciferine for the first time Nucif-erine can ameliorate sleep disorder in mice with insom-nia,possibly via serotonergic system.Nuciferine may rep-resent a novel treatment that alleviate the insomnia-like symptoms by modulating 5-HT system.
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Objective To explore the effects of high-frequency electromagnetic radiation exposure on the mood-cognitive behaviors of mice, and to provide an experimental basis for the study on radiation damage mechanism and protection. Methods The electromagnetic reverberation chamber can produce continuous and uniform high-frequency electromagnetic waves. Different groups of ICR mice were exposed to high-frequency electromagnetic radiation in this chamber for 1 d, 3 d and 7 d, and then series of behavioral tests were conducted to observe the changes in locomotor activities,depressive-like and anxiety-like behaviors, and cognitive function of the mice. Results After exposed to the high-frequency electromagnetic radiation(3 GHz,SAR 4 W/kg)4 h/d for 7 d,there was no obvious change in locomotor activity(times of grid crossing and standing up in the open field test)of the mice,while the times of entering the central region(P< 0.05)and the time duration(P< 0.05)were significantly decreased. Compared with the unexposed group, the percentage of the times of entering the open arm in the elevated-plus maze(P< 0.05)and the time duration in the open arm(P< 0.01)of the mice in the radiation group were significantly decreased. Meanwhile, the immobility time in the forced-swimming test(P< 0.01)and the tail suspension test(P < 0.05)of the mice exposed to electromagnetic radiation was significantly increased, and the discrimination index of new objects in the new object recognition test was significantly reduced(P < 0.001). Conclusions Continual exposure to high-frequency electromagnetic radiation(3 GHz,SAR 4 W/kg)can lead to anxious-depression behaviors and cognitive impairment of mice in a time-dependent manner,which provides an experimental basis for the relevant study of prevention and therapy techniques.
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Objective To observe the protective effect and mechanism of 2,3,5,4 '-tetrahydroxystilbene-2-O-beta-D-glucoside ( THSG) on atherosclerosis in ApoE konck-out mice. Methods A total of 24 ApoE knock-out mice were randomly divided into normal control group (n=8), model control group (HFD, high-fat diet, n=8) and treated group (THSG, 20 mg· kg-1, i. g. , n=8). The atherosclerosic plaque of aorta wall and aorta root were measured by oil red O staining;The expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in human umbilical vein endothelial cells (HUVEC) through C-reaction protein ( CRP) was studied by Western blotting. Results The atherosclerosis plaque in normal control group was not observed. The lipid accumulation decreased in the aorta and the plaque areas in the aortic sinus in THSG treated-group compared with model control group. Moreover, THSG down-regulated CRP-induced LOX-1 expression in HUVEC. Conclusion The atheroscletosis plaque in ApoE knock-out mice was decreased by THSG. The mechanism might be related to the inhibition of the expression of LOX-1 protein.
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OBJECTIVE To explore the antidepressant effect and the underlying mechanisms of schisandrin (SCH), a component of the fruits of Schizandra chinesis. METHODS The forced swimming test (FST) and tail suspension test (TST) in mice were used to evaluate the antidepressant activity of SCH (5, 10, and 30 mg · kg-1) following single administration intragastrically, and the locomotor activity was investigated to exclude its neural excitatory effects. Effects of SCH on neural monoamine systems were studied in two pharmacological models, including reserpine induced monoamine depletion test and yohimbine toxicity potentiation test. RESULTS In behavioral despair models, SCH (30 mg·kg-1) signif?icantly decreased the immobility time in the TST and FST (P<0.05) compared with normal control group. Results of the locomotor activity experiment showed that SCH had no excitatory or inhibitory actions on the central nervous system. In the reserpine reversal experiment, SCH (30 mg · kg-1) antagonized thepalpebral ptosis and akinesia symptoms caused by reserpine(2.5 mg · kg-1) treatment (P<0.05) compared with model group, but had little effect on the drop of the anal temperature. Moreover, SCH did not increase the lethality caused by subcutaneous injection of yohimbine (30 mg · kg-1)at the threshold lethal dosage. CONCLUSION SCH exerts potential antidepressant-like effect in mice.
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OBJECTIVE To study the influence of glycogen synthase kinase3β (GSK3β) over expres?sion in the hippocampus on the antidepressant and anxiolytic effects of total flavoids from Xiaobuxin Tang (XBXT-2). METHODS Adeno-associated virus containing GSK3β(S9A) mutation was microinjected into the hippocampus. After three weeks of recovery, GSK3βand p-GSK3βwere detected by Western blotting, and open field test (OFT) was used to evaluate the locomotor activity. Then, AAV group and GSK3β over expression group were divided into administration group and solvent group, respectively. XBXT-2 (100 mg · kg-1) and solvent were ig administered chronically. After 14 d and 16 d of administra?tion, the tail suspension test (TST) and forced swimming test (FST) were used to investigate the influence of GSK3βover expression on the antidepressant effect of XBXT-2, respectively. After 18 d and 20 d of administration, the elevated plus maze test (EPMT) and staircase test (ST) were used to investigate the influence of GSK3β over expression on the anxiolytic effects of XBXT-2, respectively. RESULTS Western blotting analysis showed that the protein level of GSK3βincreased significantly in GSK3βover expression group (P<0.01) compared with AAV group, but there was no significant difference in p-GSK3β. In OFT, the number of crossings and rearings showed no difference between AAV group and GSK3β over expression group. The results of TST and FST showed that compared with AAV group, the immobility time was significantly reduced in AAV+XBXT-2 group (P<0.05, P<0.01), but compared with GSK3β over expression group, the immobility time showed no difference in GSK3β over expression+XBXT-2 group. In EPMT, compared with AAV group, the percentage of entrances and time into open arms in AAV+XBXT-2 group was significantly increased (P<0.01, P<0.05), but compared with GSK3βover expression group, these indexes showed no difference in GSK3βover expression+XBXT-2 group. In ST, compared with AAV group, the number of rearings was significantly reduced in AAV+XBXT-2 group (P<0.05), but there was no difference between GSK3β over expression+XBXT-2 group and GSK3βover expression group. CONCLUSION GSK3βover expression in the hippocampus can reverse the antidepressant effects of XBXT-2 in the TST and FST, and the anxiolytic effects in the EPM and ST.
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OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.
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OBJECTIVE To study the antidepressant effects of ammoxetine(AMX)and the underlying mechanisms. METHODS Two behavioral despair models,the tail suspension test (TST) and the forced swimming test(FST),were used to evaluate the antidepressant-like effects of AMX 2.5-20 mg · kg-1 following oral administration. Monoamine neurotransmitter p-chloro-phenylalanine(p-CPA)andα-methyl-p-tyrosine(AMPT) depletion models in mice were used to investigate the effects of AMX on levels of 5-serotomin(5-HT)and norepinephrine(NE)in the brain. RESULLTS The results of behavioral study showed that compared with normal control group,AMX(10 and 20 mg · kg-1)reduced the immobility time of mice by 51.4% and 80.7% in the TST(P<0.05,P<0.01) or by 48.0% and 66.2% in the FST (P<0.05),respectively. Locomotion activity test indicated that AMX did not increase or decrease the movement distance of mice,demonstrating that AMX had no excitatory or inhibitory actions on the central nervous system. Moreover,AMX(5,10 and 20 mg·kg-1)exerted antidepressant effects in the p-CPA induced 5-HT depletion model and AMPT induced NE depletion model,as evidenced by the significantly reduced immobility time,ie,63.9%,93.4%,90.5% and 61.9%,77.2%,100% reduction in the TST (P<0.01),respectively,and AMX at the dose of 20 mg·kg-1 significantly increased the concentrations of 5-HT and NE by 144.7% and 57.2% in the mouse brain(P<0.05) ,respectively. CONCLUSION AMX has strong antidepressant-like effects in behavioral despair models and monoamine neurotransmitter depletion models in mice,which is involved in the increased levels of 5-HT and NE in the brain.
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Objective To investigate the role of transcriptional-coactivator with PDZ-binding motif( TAZ) in genistein-induced osteoblastogenic differentiation of mouse bone marrow-derived mesenchymal stem cells ( BMSCs) .Methods Mouse BMSCs were cultured in phenol red-freeα-MEM containing osteogenic supplements for inducing osteogenic differentiation.BMSCs were transfected with siRNA-TAZ and treated with genistein.The temporal sequence of osteoblastic differentiation in BMSCs cultures was assayed by measuring alkaline phosphatase activity (ALP) and calcium deposition.The mRNA expression of bone sialoprotein ( BSP) and osteocalcin ( OC) were detected by reverse transcription-polymerase chain reaction(RT-PCR).The binding interaction between TAZ and cbfa1 was identified by co-immunoprecipitation.Results TAZ expression was detected during the induction of osteogenic differentiation, the ALP activity and calcium deposition were significantly decreased in BMSCs which were transfected with siRNA-TAZ.Genistein(0.01-1 μmol/L) exhibited a dose-dependent effect on TAZ expression in mouse BMSCs cultures.Treatment with genistein ( 1 μmol/L ) resulted in increased ALP avtivity and calcium deposition of BMSC cultures as function of time.Genistein(1μmol/L) also promoted the nuclear localization of TAZ and augmented the interaction between TAZ and cbfa1, and by which upregulated cbfa1-mediated gene expression such as BSP and OC.However, the ALP avtivity and calcium deposition, as well as the expression of BSP and OC were not promoted by genistein in BMSCs transfected with siRNA-TAZ.Conclusion These data suggest that the TAZ plays an important role in genistein-induced osteoblastic differentiation of mouse BMSCs cultures.
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OBJECTIVE To investigate the relationship between the anti-post-traumatic stress disorder(PTSD)effect of sertraline and nitric oxide in fear conditioning rats. METHODS Conditioned fear stress was established by electric shock with a cue tone,and fear extinction training was carried out by giving the rats only tone signals the next day. The rats were treated with sertraline(15 mg · kg-1) intragastrically within 1 h before the experiment for 8 d. Freezing time was tested at the 1st,4th and 7th day after the extinction training in rats. The NO contents were detected by Griess method and the nNOS and iNOS level on amygdala was detected by Western blotting. RESULTS The behavior tests showed that compared with normal control group ,the freezing time was significantly increased in extinction control group and extinction training group(P<0.01),indicating that the conditioned fear model of rats was successfully established. At the 1st and 4th day after conditioned fear extinction training in the rats,freezing time in sertraline(15 mg·kg-1)group was decreased compared with extinction training group (P<0.05). At the 7th day,the freezing time was significantly decreased(P<0.01),indicating that ser?traline reversed the fear response. At the same time,the contents of NO,nNOS and iNOS on amygdala of rats in sertraline group were lower than that in extinction training group(P<0.01). CONCLUSION Sertraline can promote extinction of conditioned fear memory,suggesting that sertraline has anti-PTSD effects on the model of fear condition in rats. The underlying mechanisms may be connected with NO.
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Bipolar disorder(BD)is a serious mood disorder with high prevalence,morbidity and mortality rates. Glycogen synthase kinase-3β(GSK-3β) is a multifunctional serine/threonine protein kinase that is generally located in eukaryotic cells with such functions as the adjustment of the synthe?sis of glycogen metabolism,cell proliferation and differentiation and gene expression. It is involved in multiple signaling pathways and regulates cell signaling proteins,structural proteins and transcription factors through phosphorylation,affecting the survival of the neurons and plasticity. According to gene poly?morphism and clinical studies,GSK-3β may be associated with BD. As a GSK-3β inhibitor,lithium is an effective BD therapeutic drug,and the small molecule inhibitor targeting GSK-3βis also a hotspot of BD treatment. GSK-3βmay be a potential target in the treatment of BD.
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Aim To investigate the effect of the total flaconoids extracted from Xiaobuxin-Tan g ( XBXT-2 ) on the hyperactivity of hypothalamic-pituitary-adrenal axis in mouse learned helplessness model. Methods Learned helplessness was induced by inescapable foot shock stress over 1h session for 5 days. After screen-ing, we divided learned helplessness mice into five groups:IS, inescapable shock;Dlx, dulxetine(20 mg ·kg-1);XBXT-2(25,50 mg·kg-1). Latency to es-cape shocks and escape failure had been recorded. During the test, Dlx(20 mg·kg-1 ) and XBXT-2(25, 50 mg·kg-1 ) were administered intragastrically once daily for four days. Serum corticosterone level and ad-renocorticotropic hormone ( ACTH ) level were meas-ured by ELISA, and expression of glucocorticoids re-ceptor ( GR) α/β and brain-derived neurotrophic fac-tor ( BDNF ) in hippocampus was determined using Western blot method. Results XBXT-2 (25,50 mg· kg-1 ) or duloxetine treatment showed antidepressant effect in mouse learned helplessness model, as demon-strated by the decreased escape failure and escape la-tency. Our ELISA results showed that XBXT-2 or du-loxetine significantly decreased serum corticosterone level and its upstream stress hormone ACTH level in learned helplessness mice. Furthermore, Western blot result demonstrated XBXT-2 treatment increased GRs and BDNF expression in hippocampus. Conclusions XBXT-2 produces significant antidepressant effect on learned helplessness mice. In addition, the modulation of HPA axis produced by XBXT-2 may be important mechanism underlying its antidepressant-like effect in mouse learned helplessness model.
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Depression is a serious mental disorder characterized by lasting anhedonia and anorexia .The pathophysiology of depression is complicated , which is related to many neuroendocrine disturbances .Increased levels of glucocorticoid hor-mones and hyperactivity of the hypothalamus pituitary adrenal ( HPA) axis are the most consistent and typical pathophysio-logical alternations in patients with major depression , which are possibly caused by altered functions of the receptor of glu-cocorticoid hormones , the glucocorticoid receptor ( GR) .Promoting the expression and function of GR and restoring the im-paired feedback inhibition of the HPA axis seem to be particularly important for the therapeutic efficacy of antidepressants . In this review, the role of GR in the development and resolution of depression is discussed .
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OBJECTIVE Toexploretheantidepressanteffectsofalbiflorinandtheinvolvementof hypothalamic-pituitary-adrenocortical (HPA) axis function in its antidepressant potency.METHODS Two weeks after the olfactory bulbectomized (OB)surgery,albiflorin (2.5 ,5.0 ,10.0 mg·kg -1 ,ig) and imipramine 5.0 mg·kg -1 (ig)were given to rats twice a day for 14 d.The open-field test was con-ducted to evaluate the move ment distance,move ment ti me and velocity of olfactory bulbecto mized rats and sham-operated rats.The serum levels of corticosterone(CORT)and adrenocorticotropic hormone (ACTH)in rats were measured by the enzyme linked immunosorbent assay.The expression levels of glucocorticoids receptor (GR)in the hippocampus of the rats were analyzed using Western blot proce-dures.RESULTS Comparedwithsham-operatedrats,movementdistance,movementtimeandveloci-ty of the OB rats were significantly increased (P<0.01 ).Albiflorin 1 0.0 mg·kg -1 significantly reduced the movement distance,movement time and velocity of OB rats (P<0.05)after being given for 7 d. The movement properties were significantly reduced by albiflorin 5.0 and 10.0 mg·kg -1 when given for 14 d (P<0.05).The OB rats demonstrated significantly increased levels of serum CORT and ACTH (P<0.01 )and decreased GR expression in the hippocampus (P<0.01 ).Albiflorin 2.5,5.0 and 10.0 mg·kg -1 significantly reduced the serum CORT and ACTH levels (P<0.05),while albiflorin 5.0 and10.0mg·kg-1increasedtheexpressionofhippocampalGR(P<0.05).CONCLUSION Albiflorin may have re markable behavioral antidepressant effects on olfactory rats and one of the related mecha-nis ms may be its regulation of the hyperactivity of HPA axis function.
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An on-line solid phase extraction ( SPE ) coupled with HPLC-MS/MS method was developed to determine S-ammuxetine and R-ammuxetine in rat plasma. The sample preparation consisted of the following steps:A protein precipitation extraction used methanol and acetonitrile ( 50:50 , V/V ); an on-line SPE treatment to remove most matrixes in plasma;an enrichment and separation step used a C18 analytical column. S-and R-ammuxetine were determined by tandem mass spectrometry. The SPE column was a Retain PEP Javelin (10 mm × 2. 1 mm × 5 μm), while the chromatographic separation was achieved using a ZORBAX SB-C18 (50 mm × 2. 1 mm × 3. 5 μm) analytical column with an isocratic mobile phase composed of acetonitrile-water-formic acid (40:60:0. 1, V/V/V, 0. 3 mL/min). The selected reaction monitoring mode of the positive ion was performed and the precursor to the product ion transitions of m/z 292 . 1/154 . 0 and m/z 260. 4/116. 2 were used to measure S-ammuxetine, R-ammuxetine and internal standard (propranolol). The method was linear over a concentration range from 0 . 2 to 1000 μg/L with the correlation coefficients of 0 . 9903 and 0 . 9951 . The average intra-day precision values were 1 . 2% -12 . 0% for S-ammuxetine and 0. 4%-11. 2% for R-ammuxetine, respectively. The average recoveries were 94. 2%-101. 6% for S-ammuxetine and 94. 3% -109. 4% for R-ammuxetine. Compared to the literature, the sensitivity of this method increased dramatically. The present method has been successfully applied to the preclinical rat research of ammuxetine isomers following intragastric administration.
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In this paper, duloxetine was chosen as the lead compound. The pharmacophores with 5-HT(1A) antagonism activity were used to replace the naphthyl of duloxetine. A series of duloxetine derivatives had been designed and synthesized and whose structures were confirmed with elemental analysis, MS and H NMR. All synthesized compounds were tested by tail suspension test and forced swimming test in vivo. The test results revealed that most of the compounds have shown better activity than duloxetine at the same dosage. Some of them are worth to be studied further.
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AIM Xiaobuxin-Tang (XBXT) is a traditional Chinese herbal decoction which is composed of Haematitum, Flos Inulae, Folium Phyllostachydis Henonis and Semen Sojae Preparatum. The present study was to investigate if the total flavonoids extracted from XBXT (XBXT-2) had antidepressant effect. METHODS Forced swimming tests in mice and rats, and learned helplessness (LH) model of rats were adopted to affirm the antidepressant effect of XBXT-2 with the test on spontaneous motor activity. Plasma corticosterone level in the LH rats was measured with ELISA. RESULTS Single administraton of XBXT-2 at the doses of 50 and 100 mg·kg-1 (ig) significantly decreased the duration of immobility time in the forced swimming tests in mice and rats. Researches on LH model of rats indicated that XBXT-2 at doses of 50 and 25 mg·kg-1 markedly reduced the number of escape failure in shuttle box. Meanwhile, the plasma corticosterone level of the LH rats was significantly decreased. XBXT-2 50-200 mg·kg-1 had no effects on spontaneous motor activity in mice. CONCLUSION XBXT-2 possesses significant antidepressant-like effect. The mechanism may involve the inhibition of the hyperaction of the hypothalamic-pituitary-adrenal axis.
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Existing antidepressants exhibit delayed onset of action,which can decrease the compliance of the patients and enhance the risk of suicide.How to produce early-onset antidepressants with higher efficacy and lower adverse reactions has become a crucial point in the research of antidepressants.It has been demonstrated that selective 5-HT1Aantagonist,?2 antagonist and 5-HT2Aantagonist can accelerate the response of classic antidepressants.Furthermore,5-HT/NE dual reuptake inhibitor and 5-HT/NE/DA triple reuptake inhibitor can also produce early onset of action.Here,several reasons for the delayed onset of action and the progress in the development of early-onset antidepressants are reviewed.
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Objective To improve the recognization of the cavitating lung cancer in CT scans.Methods From May 1996 to June 2000,37 patients out of total 271 primary lung cancers were confirmed by transthoracic needle aspiration biopsy,operation and pathlogical examination.Results There were 5 pattens cavitaties in the CT manifestations.They were 15 cases cavities with thick irregular walls,14 cases round or ovoid growths with central or eccentric cavitation,4 cases solid lobes containing cavities,2 cases thin-walled cavities resembling cysts and 2 cases fissural cavities.There were 24 cases squamous-cell carcinomas,5 cases adenocarcinomas,2 cases small-cell carcinomas,2 cases alveolar-cell carcinomas.Conclusion The cavitating lung cancer is made misdiagnosis easilier.There is important clinical value in diagnosis with transthoracic needle aspiration biopsy(TNAB).
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AIM To explore possible action mechanism of antidepressants. METHODS Using flow cytometry, the cell proliferation was detected. The proliferation of hippocampal progenitor cells and level of brain derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS Treatment with N methyl D aspartate (NMDA) 600 ?mol?L -1 for 3 d significantly decreased the percentage of S phase in PC12 cells, while in the presence of classical antidepressants, desipramine (DIM) or fluoxetine (FLU) 1, 5 ?mol?L -1 , the percentage of S phase increased. Furthermore, the proliferation of hippocampal progenitor cells, as well as the BDNF level in dentate gyrus (subgranular zone) significantly decreased in chronically stressed mice for 24 d, while chronic administration with DIM or FLU 10 mg?kg -1 (ip) normalized it. Meanwhile, the BDNF level in dentate gyrus also elevated after DIM or FLU treatments. CONCLUSION Up regulation of the hippocampal neurogenesis is the common action mechanism for antidepressants, which may be closely related to the elevation of BDNF level at the same time.