Carboxymethylation of the polysaccharide from the fermentation broth of Marasmius androsaceus and its antidepressant mechanisms

To investigate the structure-activity relationship of polysaccharide and obtain a better antidepressant polysaccharide,the antidepressant-like activity of a carboxymethyl polysaccharide(C-MEPS2)subjected to submerged fermentation was systematically studied.PC12-H cell and Kunming mice were used to investigate the differences and their mechanism in the antidepressant effects of C-MEPS2 and MEPS2.Cell experiments have showed that C-MEPS2 has a better antidepressant effect than MEPS2.C-MEPS2 could exert antidepressant effects related to catecholamine synthesis with specifi c sites of TH,D2DR,and P-CAMKII.In addition,C-MEPS2 could repair the Res-induced damage in PC12-H cell,stabilize the mitochondrial membrane potential and regulate intracellular Ca^(2+) concentration,thus reducing cell apoptosis caused by RES.Antagonists common dosing experiments on animals further proved that CMEPS2 could signifi cantly improve the antidepressant effect of derivatives without affecting the antidepressant mechanism of MEPS2.It is speculated that it may be related to carboxymethylated modifi cation.

Preparation Process,Pharmacological Activity and Molecular Mechanism of Valepotriate

In recent years,with the continuous development of the medicinal value of valepotriate and the great attention of scholars.The traditional extraction and purification process can no longer meet the current market standards and needs.The modern technology of valepotriate is of great significance to its application and development.This paper reviews the extraction and purification process,molding process and pharmacological activity of valepotriate,providing a theoretical basis for the research and application of valepotriate.

Discontinuation of antidepressant therapy among patients with major depressive disorder

Objective: Patients with major depressive disorder (MDD) often discontinue antidepressant therapy pre- maturely risking relapse, despite United Kingdom (UK) guidelines recommending therapy for up to at least six months after remission. More information is needed on the patterns of antidepressant discontinuation in UK primary care. Objectives of the study were to assess the patterns, incidence and predictors of therapy discontinuation among MDD patients initiating treatment with selective serotonin reuptake inhibitors (SSRIs). Methods: This was a retrospective cohort study using general practices registered with the General Practice Research Database (GPRD). 15,274 patients with MDD receiving a first ever prescription (index) for an SSRI between 2006-2008 were identified in GPRD. Discontinuation (including temporary gaps) and cessation of antidepressant therapy were examined over follow-up. Predictors of incidence of discontinuation in the six months after index were assessed. Results: Incidence of discontinuation of antidepressant therapy over follow-up was 80.05 per 100 person years (95% CI 78.94 - 81.17). At six months after index 42% of patients had discontinued and 33% had ceased therapy altogether. Lower discontinuation of index SSRI therapy in the first six months after initiation was associated with higher age, higher body mass index (BMI), and comorbid irritable bowel syndrome. Higher discontinuation was associated with paroxetine or fluoxetine at index, and a more recent index calendar year. Conclusions: There is a significant risk of discontinuation of antidepressant therapy in the 6 months after initiation of treatment for MDD. This finding requires awareness by the general practitioner (GP) to ensure implementation of optimal treatment regimens, and minimization of therapy non-compliance among MDD patients.

Effective treatment of depression improves post-myocardial infarction survival

AIM: To examine the contribution of treatment resistant depression(TRD) to mortality in depressed postmyocardial infarction(MI) patients independent of biological and social predictors.METHODS: This secondary analysis study utilizes the Enhancing Recovery in Coronary Heart Disease(ENRICHD) clinical trial data.From 1834 depressed patients in the ENRICHD study,there were 770 depressed post-MI patients who were treated for depression.In this study,TRD is defined as having a less than 50% reduction in Hamilton Depression(HAM-D) score from baseline and a HAM-D score of greater than 10 in 6 mo after depression treatment began.Cox regression analysis was used to examine the independent contributions of TRD to mortality after controlling for the biological and social predictors.RESULTS: TRD occurred in 13.4%(n = 103) of the 770 patients treated for depression.Patients with TRD were significantly younger in age(P = 0.04)(mean = 57.0 years,SD = 11.7) than those without TRD(mean = 59.2 years,SD = 12.0).There was a significantly higher percentage of females with TRD(57.3%) compared to females without TRD(47.4%) [χ2(1) = 4.65,P = 0.031].There were significantly more current smokers with TRD(44.7%) than without TRD(33.0%) [χ2(1) = 7.34,P = 0.007].There were no significant differences in diabetes(P = 0.120),history of heart failure(P = 0.258),prior MI(P = 0.524),and prior stroke(P = 0.180) between patients with TRD and those without TRD.Mortality was 13%(n = 13) in patients with TRD and 7%(n = 49) in patients without TRD,with a mean follow-up of 29 mo(18 mo minimum and maximum of 4.5 years).TRD was a significant independent predictor of mortality(HR =1.995; 95%CI: 1.011-3.938,P = 0.046) after controlling for age(HR = 1.036; 95%CI: 1.011-1.061,P = 0.004),diabetes(HR = 2.912; 95%CI: 1.638-5.180,P < 0.001),heart failure(HR = 2.736; 95%CI: 1.551-4.827,P = 0.001),and smoking(HR = 0.502; 95%CI: 0.228-1.105,P = 0.087).CONCLUSION: The analysis of TRD in the ENRICHD study shows that the effective treatment of depression reduced mortality in depressed post-MI patients.It is important to monitor the effectiveness of depression treatment and change treatments if necessary to reduce depression and improve cardiac outcomes in depressed post-MI patients.

Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide （YLSPS; 150, 300 and 600 mg/kg） for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS （300 and 600 mg/kg）, monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

Mechanisms of repetitive transcranial magnetic stimulation for antidepression: Evidence from preclinical studies

This review summarizes the anti-depressant mechanisms of repetitive transcranial magnetic stimulation in preclinical studies,including anti-inflammatory effects mediated by activation of nuclear factor-E2-related factor 2 signaling pathway,anti-oxidative stress effects,enhancement of synaptic plasticity and neurogenesis via activation of the endocannabinoid system and brain derived neurotrophic factor signaling pathway,increasing the content of monoamine neurotransmitters via inhibition of Sirtuin 1/monoamine oxidase A signaling pathway,and reducing the activity of the hypothalamic-pituitary-adrenocortical axis.We also discuss the shortcomings of transcranial magnetic stimulation in preclinical studies such as inaccurate positioning,shallow depth of stimulation,and difficulty in elucidating the neural circuit mechanism up-and down-stream of the stimulation target brain region.

Antidepressant and cognitive activities of intranasal piperine-encapsulated liposomes

Antidepressant and cognitive effects of piperine -encapsulated liposomes (PL) were investigated in male Wistar rats. Oral piperine (5 mg/kg body weight/day) and intranasal PL (7.2 μg/day) were randomly assigned to daily administer for 14 days to rats which were subjected to forced swimming, Mor-ris water maze and spontaneous motor behavior tests. PL significantly exhibited anti-depression like activity and cognitive enhancing effects, in comparison to the control groups after the first dose (p < 0.01) and the effects could be maintained throughout the period of study. Quantitative analysis of the brain homogenates by HPLC indicated that piperine, delivered either orally or nasally, distributed to the hippocampus at a higher extent than the cortex and that the time to peak concentration of nasal PL was shorter than for the oral piperine. Intranasal PL was, thus, potential in delivery of piperine, at a low dose, to exert its an-tidepressant and cognitive enhancing activities.

A review of studies on the therapeutic effect of vagus nerve stimulation

BACKGROUND： Vagus nerve widely innervates in the human body, and it has diverse physiological functions. Many new physiological functions are gradually found. Studies on its action mechanism have been gradually deepened. Vagus nerve stimulation （VNS） has been used for treatment of epilepsy and depression in clinic. OBJECTIVE： To retrospectively investigate the therapeutic effects and mechanism of VNS. RETRIEVE STRATEGY： A computer-based online research in Pubmed with the key words of ＂vagus nerve stimulation＂ published between February 1990 and October 2006 in English were systemically reviewed. Totally 583 articles were collected and primarily selected. Inclusive criteria： the mechanism of therapeutic effects of VNS-related literatures. Exclusive criteria： repetitive study. LITERATURE EVALUATION： According to inclusive criteria, of the 57 articles, which met the inclusive criteria, 42 were associated with the therapeutic function of VNS, and 15 with the mechanism of these related functions. DATA SYNTHESIS： Vagus nerve has special nerve innervation and wide projection with extensive physiological effects. Till now, VNS has been used in the therapy of epilepsy and depression, and exact clinical effects have been obtained. Further studies have discovered other functions of VNS, such as the effect on the memory power, cognition, and perception to pain. Thus, the studies about VNS become diverse. Just because of the special physiological functions of vagus nerve, VNS can bring some adverse reactions such as foreign body sensation, hoarseness, trigeminal neuralgia, etc. The mechanism of therapeutic function of VNS is still under exploration. CONCLUSION： As a mature surgical technique, VNS has been widely used in the therapy of epilepsy, depression, inflammation, analgesia, relieving itching, etc. Although the mechanism is still unclear, it brings obvious clinical effects.

Research Progress on Pharmacological Action of 5-O-methylvisammioside

5-O-methylvisammioside is a chemical derived from the dry root of Saposhnikovia divaricata,which has the functions of expelling pathogenic wind from body surface,removing dampness to relieve pain,and relieving convulsion.Recent studies have found that 5-O-methylvisammioside can play a variety of pharmacological effects such as anti-tumor,anti-inflammation,anti-virus and anti-depression through a variety of ways.The paper reviews the pharmacological action and mechanism of 5-O-methylvisammioside in recent years.

Recent Advances in Ketamine Research: An Update

Ketamine is a sedative N-methyl-D-aspartate receptor antagonist, considered as a dissociative anesthetic medication. Ketamine inhibits the voltage-gated Na+ & K+ channels and serotonin and dopamine re-uptake and affects specific receptors, such as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and aminobutyric acid A receptors. It is commonly administered by a parenteral route. On administration, ketamine has particular properties that are potentially involved during anesthetic induction including the enhancement of descending inhibition and anti-inflammatory effects. Recent literature reviews report that ketamine possesses various clinically beneficial properties. Sub-dissociative dose/Lower dose of ketamine (LDK) has potential as well as safe effects in clinical practice for the management of acute and chronic pain in postoperative room as well as Emergency Department (ED), along with cognitive function and depression in Psychiatric Department. Moreover, pharmacology of ketamine includes bronchodilators, neuro-protective actions, anti-shock, anti-suicide, and anti-tumor action immune system disorder. The purpose of this review is to illustrate recent advances in mechanism of action, mode of administration and indication of clinical uses of ketamine. In this article various new uses of ketamine have been shown, mainly related to its NMDAR antagonism and the clinical implementation and significance of low dose/sub dissociative dose of ketamine. In future, beyond being used as the adjuvant general anesthesia, it also can be used as a rapid acting antidepressant and anti-suicidal agent for mental disorders, and adjuvant analgesia to avoid potential risk and side effects of opioids in emergency department and in post-operative care.

Paediatric amitriptyline overdose

We report a near fatal case of paediatric amitriptyline overdose including a series of ECGs demonstrating the effects of sodium bicarbonate therapy on cardio-toxicity. We briefly discuss the role of sodium to counteract the sodium channel blockade of tricyclic antidepressants and discuss the possible utility of lipid emulsion therapy in such cases.

Anti-depression effect of Kai Xin San and research of its compatibility

Kai Xin San (KXS) is a category of traditional complex prescription that wasfirst recorded in Bei Ji Qian Jin Yao Fang by SUN Si-miao in the Tang Dynasty and then also recordedin Tai Ping Hui Min He Ji Ju Fang, Qian Jin Yao Fang and Gu Jin Lu Yan in later generations. It wasmainly used by herbalist doctors to treat symptoms including desolation, moodiness, forgetfulnessetc. , which are similar to the neurosis such as depression, anxiety and difficulty in studying andmemory in the West medicine. The former recorded formulas were all composed of ginseng, polygala,hoelen and acori graminei with different proportion. But there are no systematic studies on theclinical adaptive symptom corresponding to different matching and the best anti-depressive matchingso far. In this study, the classical anti-depressive animal model, namely, ' force swimming model'and 'suspend tail model' were adopted to appraise the anti-depressive effect of the aforementionedformulas and the pharmacodynamical distinction between the whole formula decoction and the activecombination made up with each effective component from ginseng, polygala, hoelen and acori graminewere also investigated, which would provide scientific evidence for properly using KXS in clinic.

A distinct pattern of memory and attention deficiency in patients with depression

Background Depression related cognitive deficits are frequently considered as simple epiphenomena of the disorder. However, whether or not the depression might directly bring about cognitive deficits is still under investigation. This study was to investigate the distinctpattern of cognitive deficits in patients with depression by comparing the cognitive function before and after anti-depressive drug therapy. Me^ods Sixty cases of patients, first-time diagnosed with depression, were assessed by 17-item Hamilton Rating Scale for Depression （HAMD17scale）The memory ability was tested by quantitatively clinical memory scale, while the attention ability by modified Ruff 2＆7 Selective Attention Test. Forty-two healthy volunteers were recruited as controls. The depressive patients were treated with Venlafaxine （75-300 mg/d）, Fluoxetine （20-40 mg/d）, Paroxetine （20-40 rag/d）, and Sertraline （50-150 mg/d）. After 12 weeks treatment, patients were tested again by HAMD17scale, quantitatively clinical memory scale, and modified Ruff 2＆7 selective attention test to assess the effect of anti-depressive drugs on cognitive deficits. Results The memory quotient （MQ） was significantly lowered in depressive patients. The selection speed was also significantly decreased and the number of missing and error hits increased in the depression group as compared to control. However, there was no significant difference in clinical memory scale and Ruff 2＆7 selective attention test between mild-to-moderate and severe depression group. Importantly, after anti-depressive drug therapy, the HAMD17 scale scores in depressive patients were significantly decreased, but the MQ, directional memory （DM）, free recall （FR）, associative learning （AL）, and face recognition were comparable with those before the treatment. Furthermore, the selection speed and the number of missing and error hits were also not significantly different after anti-depressive drugs treatment. Conclusions Depressive patients suffer from short-term memory deficits, and attention extent, stability and rearrangement deficiency. Even though anti-depressive drugs sufficiently relieve the cardinal presentation of depression, they could not successfully alleviate the accompanying cognitive deficits. This might indicate a distinct pattern of cognitive deficits in patients with depression.