Alzheimer′s disease(AD)is one of the most common causes of cognitive impairment.“Aβhypothesis”and“tau protein aggregation hypothesis”are two representative hypotheses in relation to AD pathology. But recently,therapeutic strategy target?ing on reducing Aβdeposition failed in clinical trials. On the other hand,as the phosphorylation of tau protein is regulated by multiple upstream kinases,inhibition of a single kinase usually cannot effectively suppress the aggregation of the tau. While blocking multiple kinases at the same time will produce serious side effects. Currently,targeting on Aβand tau protein get into awkward situations. In view of this,researchers are looking for new drug targets for improving cognitive function. Phosphodiesterase 4(PDE4 4)is an enzyme responsible for the hydrolysis of cAMP in the body. There are four subtypes for PDE4,and PDE4A,B and D are highly expressed in the central nervous system. Inhibition of PDE4 causes activation of cAMP/PKA/CREB/BDNF signal pathway,which is beneficial for the strengthening and consolidation of learning and memory. This review will focus on the most recent evidence regarding the role of PDE4 in learning and memory.

Cell adhesion molecules (CAMs) are involved in glycoproteins expressed on cell surfaces which play an essential role in clinical disorders. At present, there are several groups of anti inflammatory drugs interfere with the expression of CAMs either directly or indirectly. This paper reviews the study of recent finding pharmacological agents associated with CAMs.

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by cognition impairment and behavioral abnormalities.While the mechanisms involved in AD remain unclear,various hypotheses have been proposed regarding pathogenesis of AD,among which the oxidative stress hypothesis has attracted more and more attention.In the present article,the relationship between oxidative stress and AD is reviewed,including sources of neuronal oxygen radical generation,the link of oxidative stress to pathogenesis of AD,preclinical and clinical studies of AD,therapeutic effects of antioxidants and phosphodiesterase inhibitors on AD.

Objective To investigate the effect of bevacizumab on apoptosis of drug resistant nasopharyngeal carcinoma(NPC) cells in vitro.Methods The human nasopharyngeal carcinoma(NPC) cell line CNE2 and its cisplatin-resistant CNE2/DDP cells were treated with bevacizumab and DDP in various concentrations.The lethal effects of the both drugs and the apoptosis rates on CNE2/DDP cells were then measured separately with MTT assay and flow cytometry,the mRNA expressions of Bcl-2 and Bax in CNE2,CNE2/DDP and CNE2/DDP/Bev cells were detected with semi-quantitative RT-PCR.Results The killing rate in 10?g/ml bevacizumab group was similar to that of blank group(0.0?4.1% vs.5.2?4.3%,P=0.180),while the rates of combination of 10?g/ml bevacizumab and DDP(0.1?g/ml and 0.2?g/ml,separately) were higher than that of using DDP only(42.3?6.5% vs.34.4?5.4%,P=0.041;62.6?5.5% vs.50.0?5.9%,P=0.009).The apoptotic rate of CNE2/DDP,which was caused by combining 0.1?g/ml DDP and 10?g/ml bevacizumab,was much higher than what was produced by DDP alone(87.29?3.38% vs.50.58?8.83%,P=0.049).By means of semi-quantitative RT-PCR assay,the expressions of Bcl-2 mRNA in CNE2,CNE2/DDP and CNE2/DDP/Bev cells were 0.613,0.952 and 0.135,respectively.Meanwhile,the expressions of Bax mRNA were 0.665,0.387 and 1.751,separately.Conclusion Bevacizumab can greatly increase the drug sensitivity of CNE2/DDP cells to DDP;apoptosis is inhibited in MDR cells,but it can be promoted by bevacizumab.

Aim Pharmacological intervention is one of important strategies to deal with spinal cord injury.The effect of Pharmacological intervention has highly differentiated features because of complex physiopathology mechanisms in SCI.Moreover contraindications,complications having different features,it is constantly the focal point in the selection of pharmacological intervention to protect spinal cord,attenuate secondary injury and promote injuried neuron regeneration.At present only several of those have been applied in clinic and the majority are still being carried out in clinic trial stage,even preclinical animal experiment stage.This paper made a particular review of the current situation in pharmacological intervention for spinal cord injury.

This paper described the progress in therapeutics of drug dependence by opioids, involved in usages of opiate receptor agitations, non-opiate receptor agitations, non-drug treatment, and immunosuppressive therapy.

AIM: To explore the effects of Compound Yi-Zhi (YZC) on learning and memory capacity and free radical metabolism in D-galactose induced mice dementia model. METHODS: The mice dementia model was induced by a daily D-galactose 0.15 g?kg -1 sc for 45 d and after 5 d D-galactose injection, the mice were treated with three doses of YZC once a day for 40 d. In order to find out the influence of YZC on the models learning and memory capability and free radical metabolism system, Y-maze test was introduced for the former and superoxide dismutase (SOD) and malondialdehyde (MDA) tests for the latter. RESULTS: Compared with the D-galactose model group, three doses of YZC administration ( 0.108, 0.217, 0.433 g?kg -1) were all shown to significantly reduced the times of learning/memory in Y-maze test from 31.35? 8.97/ 17.12? 5.57 to 19.67? 8.07/ 11.27? 6.65, to 14.00? 6.84/ 8.29? 5.95, and to 11.41? 5.99/ 6.24? 4.97, respectively. For SOD, the administrations of 0.108 and 0.433 g?kg -1 YZC could increase the activity of SOD from 17.69? 3.14 to 26.94? 4.46, and to 21.33? 3.63 nU?mg -1 pro. While for MDA, all the three doses of YZC could decrease the level of MDA from 4.08? 0.88 to 2.82? 0.75, to 2.10? 0.42, and to 2.35? 0.39 nmol?mg -1 pro in the mice brain tissue, respectively. CONCLUSION: YZC can improve the D-galactose induced learning and memory dysfunction, and the action may be related to the improvement of antioxidase activity in the model mice brains.

OBJECTIVE: To observe the effects of ginkgolide (GL) on the cerebral blood flow in dogs. METHODS: Dogs anesthetized with sodium pentobarbital were randomly divided into 5 groups, with 4 dogs in each group. Ginkgolide of 4.86, 14.6 and 43.7 mg/kg and Xingling Granule of 0.22 g/kg were administered by gavage to the dogs in each of 4 groups. The dogs in the other group were administered with edible oil (1 ml/kg) as control group. The cerebral blood flow, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure and electro-cardiogram of the dogs were measured at different times after the administration. RESULTS: Ginkgolide of 4.86, 14.6 and 43.7 mg/kg had no obvious effects on the blood pressure and the heart rate. Ginkgolide of 14.6 and 43.7 mg/kg increased the cerebral blood flow 90 minutes after administration, and ginkgolide of 43.7 mg/kg obviously decreased the cerebral vascular resistance 150 minutes after administration. CONCLUSION: Ginkgolide can increase the cerebral blood flow and decrease the cerebral vascular resistance, and it has no obvious effects on blood pressure and heart rate in dogs.

BACKGROUND: The upward attack of drug-heat is a special type of syndromes of coexistence of cold and heat, it influence the treatment and conversion of the primary disease.OBJECTIVE: To investigate the pathophysiological basis of upward attack of drug-heat.DESIGN: A randomized and controlled observation. SETTING: Department of Traditional Chinese Medicine (TCM) of the People' s Central Hospital of Huizhou City.PARTICIPANTS: Totally 427 patients with cold syndrome, visiting on Department of TCM of the People's Central Hospital of Huizhou City from January 1996 to December 2001, were given warm-heat remedy. Among them 66 cases, 30 males and 36 females, got upward attack of drug-heat during the process of treatment were enrolled. All these subjects, according to their visiting order, at a ratio of 2:1, were chosen as treatment group (44 cases) and control group (22 cases).METHODS: For the patients in treatment group: Rhubarb 6 g was added boiling water 100 mL and soaked for 8 minutes, then the soaking solution was given to the patients, once a day, for 3 days successively. For patients in control group: Table salt 6 g was added boiling water 100 mL for soaking for 8 minutes, after the salt was completely dissolved, the solution was given to the patients, once a day for 3 days successively. The patients of the two groups were at the same time given remedy to treat cold syndrome. The changes of free triiodothyronine (FT3), free thyronine (FT4), high sensitizing thyroid-stimulating hormone (HS-TSH) and cortisol of the patients were detected before and after administration of warm-heat remedy, before and after medication with rhubarb. MAIN OUTCOME MEASURES: ① The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of warm-heat remedy. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after ad ministration of rhubarb. ③ Comparison of the therapeutic effects in the two groups.RESULTS: All 66 patients involved entered the final result analysis. ①The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of warm-heat remedy: FT3 and FT4 were decreased as compared with those before treatment [(2.51±1.20),(6.50±2.30); (10.01±3.21), (15.50±6.31) pmol/L], but HS-TSH and cortisol were increased as compared with those before treatment [(8.25 ±3.75),(4.11±1.75) mU/L; (0.56±0.17), (0.43±0.10) μmol/L]. ② The changes of the relevant hormones of the patients with upward attack of drug-heat before and after administration of rhubarb: FT3 and FT4 ywere increased as compared with those before treatment[(4.71 ±1.56), (2.45±1.25); (14.21 ±4.61),(10.21±3.52) pmol/L], but HS-TSH and cortisol were decreased as compared with those before treatment [(6.24±2.25), (8.35±3.51) mU/L; (0.48±0.10),(0.60±0.17) μmol/L]. ③ Comparison of the therapeutic effects in the two groups: The rate of excellenly effect in treatment group was obviously higher than that in control group (33%, 5%).CONCLUSION: The pathophysiological basis of upward attack of drug heat is stress state of the body, the secretions of the pituitary-thyroid axis play a role of physiological protection, the adrenocortical function is hyperactive, and rhubarb can control this stress state through inhibiting the metabolism of the body.

Objective To investigate the clonal origin of malignant cells in multifocal urothelial carcinoma. Methods p53 protein expressions were detected by immunohistochemistry in 22 pieces of tumor tissues from 10 patients with urothelial neoplasms.Mutation in p53 was inferred on the basis of immuno staining . Results The p53 protein expression of various tumors in the same patient completely matched, reflecting that the gene status of the multifocal tumor being the same. Conclusions The results strongly support the view that multifocal urothelial tumors are derived from the monoclonal cell.