Prostaglandin (PG) D_2 is one of unsaturated fatty acids with 20 carbon atoms, which is synthesized by PGD synthase (PGDS) in the brain. PGD_2 has been identified to be a sleep-inducing substance that becomes bound to the DP receptor (DPR) exclusively localized on the surface of the basal forebrain, leading to an increase in extracellular adenosine levels there. Through A_ 2A receptors (A_ 2A R), the adenosine activates neurons in the ventrolateral preoptic area (VLPO), a putative sleep center, and inhibits neurons in the histaminergic tuberomammillary nucleus (TMN), a putative wake center, via GABA to induce sleep. Studying the effect and the molecular mechanisms of sleep-induced by PGD_2 would be helpful in the development of novel sleeping drugs for more rational treatment of sleep disorders.

AIM: To investigate the effect of prostanoid DP receptors (DPR) on sleep-wake regulation in mice. METHODS: Under pentobarbital anesthesia, mice were chronically implanted with electroencephalogram (EEG) and electromyogram (EMG) electrodes for polysomnographic recordings. The spontaneous sleep-wake cycles were monitored continuously by EEG/EMG recording system for 24 h beginning at 800 p.m. and analyzed by SLEEPSIGN software in DPR knock out (KO) and wild type (WT) mice. RESULTS: DPR-KO mice exhibited a similar circadian rhythm of sleep-wake cycles to WT mice. The amounts of rapid eye movement (REM) sleep or non-REM (NREM) sleep during both the light and dark periods were identical between the DPR-KO and WT mice. Whereas, an increase in the episode number of wakefulness and a shortage in the duration of NREM sleep were found in DPR-KO mice during the light period compared with WT mice. Moreover, DPR-KO mice showed lower activity in delta-wave component in NREM sleep and higher activity in theta-wave component in REM sleep than WT mice. CONCLUSION: DPR plays a crucial role in mediating the prostaglandin D2-induced sleep. Deficiency of DPR results in the low intensity and fragmented diurnal NREM sleep and the high vigilance REM sleep, with the normal circadian rhythm of sleep in mice.

This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream signal molecules in the hippocampus of Alzheimer's disease (AD) rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid(1-42) (Abeta(1-42)) and divided randomly into 3 groups: AD model group, peoniflorin low-dose (15 mg x kg(-1)) group and peoniflorin high-dose (30 mg x kg(-1)) group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered (ip) once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthethase (gamma-GCS) mRNA by reverse transcription PCR, determining the contents of glutathione (GSH), malondialdehyde (MDA) and carbonyl protein (CP) using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein (NAIP) and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and gamma-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Abeta(1-42)-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.

The paper aims to explore the studying method for the pharmacokinetics of drugs in target organs, the pharmacokinetic process of tramadol hydrochloride in the extracellular fluid of frontal cortex (FrCx) of mice was investigated. Six male mice (Kunming strain) were anaesthetized (urethane, 1.8 g x kg(-1), ip) and secured on a stereotaxic frame. A microdialysis probe was implanted into the FrCx and perfused with artificial cerebrospinal fluid at a flow rate of 2 microL x min(-1). One hour later, mice were administrated (ip) with tramadol hydrochloride (50 mg x kg(-1)) and dialysates were collected continuously at 12-min intervals (24 microL each) for 6 h. The tramadol concentration in dialysates was determined by HPLC-Ultraviolet detection method, and the concentration-time curve and pharmacokinetic parameters of tramadol were calculated with DAS software. The results showed that the pharmacokinetic process of tramadol in the FrCx extracellular fluid of mice was fitted to a two-compartment open model, and the main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-infinity) were (0.27 +/- 0.05) h, (2.72 +/- 0.24) h, (0.50 +/- 0.10) h, (2 110.37 +/- 291.22) microg x L(-1) and (4 474.51 +/- 441.79) microg x L(-1) x h, respectively. In conclusion, a studying method for pharmacokinetics of drugs in the target organ is established, which is simple and feasible. Tramadol hydrochloride shows a two-compartment model in the extracellular fluid of the mouse FrCx, and the distribution- and elimination half-life are 0.5 h and 2.7 h, respectively.

OBJECTIVE: Embryonic stem cells (ES cells) is a special kind of cell population with totipotency and uninhibited self-renewal property. Researches on induced differentiation of ES cells were received and summed up to provide reasonable and constructive suggestions for clinical application of ES cells.DATA SOURCE: Papers published in Highwire press and Medline database were retrieved with keywords "Embryonic stem cell, differentiation, and induce" from 2000 to 2004. Additionally, papers published in Wanfang database were also retrieved with keywords "Embryonic stem cell" in Chinese from 2000 to 2004.STUDY SELECTION: Data were analyzed firstly in order to select papers related to induced differentiation. The inclusion criteria were selection of the original works, but the summaries and Meta analysis were excluded.DATA EXTRACTION: A total of 369 papers were chosen according to correlation with keywords; among them, 364 papers were in foreign language. After reading through summaries of these papers, 15 papers thoroughly discussing induced differentiation of ES cells were chosen for further intensive reading. Papers discussed various kinds of differential models, neural cells, cardiac muscle cells, epithelial cells and hematopoietic cells.DATA SYNTHESIS: The induced differential models of neural cells, cardiac muscle cells, epithelial cells and hematopoietic cells from ES cells were introduced comprehensively in the seven literatures. Based on these references mentioned above and other references which introduced cell model separately, all data were generally studied, sorted out and summed up.CONCLUSION: ES cells can be induced to be various kinds of cell models such as neural cells, epithelial cells, cardiac muscle cells and hematopoietic cells, which may be used to clarify the mechanism of cellular development and differentiation to provide good respects for clinical cellular therapy and screening of medicines.

Histaminergic neurons solely originate from the tuberomammillary nucleus (TMN) in the posterior hypothalamus and send widespread projections to the whole brain. Experiments in rats show that histamine release in the central nervous system is positively correlated with wakefulness and the histamine released is 4 times higher during wake episodes than during sleep episodes. Endogeneous prostaglandin E2 and orexin activate histaminergic neurons in the TMN to release histamine and promote wakefulness. Conversely, prostaglandin D2 and adenosine inhibit histamine release by increasing GABA release in the TMN to induce sleep. This paper reviews the effects and mechanisms of action of the histaminergic system on sleep-wake regulation, and briefly discusses the possibility of developing novel sedative-hypnotics and wakefulness-promoting drugs related to the histaminergic system.

To guide the reasonable clinical application of modafinil (MOD), pharmacokinetics and pharmacodynamics of MOD in mice and the correlation between them were investigated. Male mice (Kunming strain) were given a single oral dose of MOD (120 mg x kg(-1)). The plasma concentration of MOD was measured by HPLC and the pharmacokinetic parameters were calculated with DAS 3.0 software. For another batch of male Kunming strain mice, their locomotor activities were recorded by an infrared ray passive sensor after a same oral dose of MOD, and the synchronization and correlation between the changes of MOD plasma concentration and the locomotor activity induced by MOD were compared and analyzed. The results showed that the plasma concentration-time curve of MOD was fitted to two-compartment open model with a first order absorption. The main pharmacokinetic parameters t1/2alpha, t1/2beta, t(max), C(max) and AUC(0-inifinity) were 0.42 h, 3.10 h, 1.00 h, 41.34 mg x L(-1) and 142.22 mg x L(-1) x h, respectively. MOD significantly increased locomotor activity and the effect lasted for about 4 h. The changes of MOD plasma concentration and the locomotor activity induced by MOD were synchronous. In conclusion, there is a significant correlation between the effect of MOD and its plasma concentration after administration of 120 mg x kg(-1) in mice.

AIM: To investigate the therapeutic effect of tea polyphenols (TP) on cationic bovine serum albumin (C BSA) glomerulonephritis. METHODS: C BSA glomerulonephritic model was induced in rabbits. TP in three different doses (30, 100 and 300 mg?kg -1 ) was administered (ig) once daily for 14 days. RESULTS: TP not only significantly reduced the urinary protein excretion, decreased blood urea nitrogen (BUN) and plasma creatinine (Cr) levels, but also significantly relieved gloermular lesions in the rabbits treated and there was a significant dose dependent relationship between high dosage (300 mg?kg -1 ) and low dosage ( 30 mg?kg -1 ). CONCLUSION: TP can reduce proteinuria, suppress the development of glomerular impairments, and ameliorate the kidney function of rabbits with C BSA glomerulonephritis.

Objective: To investigate the long-term effect of submandibular salivary gland transfer on xerostomia induced by radiation in patients with nasopharyngeal carcinoma (NPC). Methods: A total of 70 eligible patients with NPC were divided into the test group (36 cases) and the control group (34 cases). In the test group, the submandibular salivary glands were transferred to the submental space before conventional radiotherapy (XRT) and shielded during XRT. Submandibular gland function and salivary fluid before and after radiotherapy, questionnaire of xerostomia at 60 months after XRT, and 5-year survival rate were compared between the two groups. Results: At 5 years after XRT, the trapping and excretion function of submandibular glands were significantly better in the test group (P=0.000 and P=0.000, respectively). The mean weight of saliva after XRT was greater in the test group than in the control group (1.65gvs.0.73g, P=0.000). Incidence of moderate to severe degree of xerostomia was significantly lower in the test group than in the control group (12.9%vs.78.6%, P=0.000). No significant difference was found in 5 year survival rate between the two groups (86.1%vs.82.4%, P＞0.05). Conclusion: Submandibular gland transfer procedure is safe for NPC patients. It can prevent XRT induced xerostomia and improve the quality of life of NPC patients.