Enhancement of oligodendrocyte autophagy alleviates white matter injury and cognitive impairment induced by chronic cerebral hypoperfusion in rats

Cognitive impairment caused by chronic cerebral hypoperfusion (CCH) is associated with white matter injury (WMI), possibly through the alteration of autophagy. Here, the autophagy-lysosomal pathway (ALP) dysfunction in white matter (WM) and its relationship with cognitive impairment were investigated in rats subjected to two vessel occlusion (2VO). The results showed that cognitive impairment occurred by the 28th day after 2VO. Injury and autophagy activation of mature oligodendrocytes and neuronal axons sequentially occurred in WM by the 3rd day. By the 14th day, abnormal accumulation of autophagy substrate, lysosomal dysfunction, and the activation of mechanistic target of rapamycin (MTOR) pathway were observed in WM, paralleled with mature oligodendrocyte death. This indicates autophagy activation was followed by ALP dysfunction caused by autophagy inhibition or lysosomal dysfunction. To target the ALP dysfunction, enhanced autophagy by systemic rapamycin treatment or overexpression of Beclin1 (BECN1) in oligodendrocytes reduced mature oligodendrocyte death, and subsequently alleviated the WMI and cognitive impairment after CCH. These results reveal that early autophagy activation was followed by ALP dysfunction in WM after 2VO, which was associated with the aggravation of WMI and cognitive impairment. This study highlights that alleviating ALP dysfunction by enhancing oligodendrocyte autophagy has benefits for cognitive recovery after CCH.

Comparative study on efficacy and safety of different routesfor vinpocetine injection by intravenous or trans-angiographiccatheter on cerebral vasospasm following embolization of ruptured aneurysm / 中国药理学通报

Aim To evaluate the efficacy and safety of different routes for vinpocetine injection by intravenous or trans-angiographic catheter on cerebral vasospasm(CVS).Methods A total of 105 aneurysmal subarachnoid hemorrhage(aSAH)patients with CVS following intracranial aneurysm embolization were chosen and randomly divided into group C, B and A, with 35 cases in each group.Patients in group C were treated with 3H therapeutic regimen, while those in group B and A were with 3H therapeutic regimen plus vinpocetine by intravenous injection or trans-angiographic catheter, respectively.The index including middle cerebral artery(MCA) blood flow velocity, National Institutes of Health stroke scale(NIHSS) score, Glasgow outcome scale(GOS) grading, clinical efficacy, hypotension rate and rehaemorrhagia rate were detected and compared among three groups.Results After the 7 d and 14 d treatment, the MCA blood flow velocity of group A and B was observed to be significantly lower than that of group C(P0.05) observed in the hypotension rate between group A and C.Also, there was no statistical difference(P>0.05)found in the rehaemorrhagia rate among three groups.However, the GOS grading of group A and B was significantly better than that of group C(P<0.05), and the grading of group A was significantly better than that of group B(P<0.05)after 3 months treatment.Conclusions Using vinpocetine by intravascular injection or by trans-angiographic catheter could be the efficient treatment for the CVS after intracranial aneurysm embolization, and vinpocetine injection by trans-angiographic catheter is the better mode of administration with the consideration of efficacy and safety.

Comparative study of extracorporeal shock wave lithotripsy one day before percutaneous nephrolithotomy for complicated renal calculi / 中国内镜杂志

Objective To discuss whether preoperative extracorporeal shock wave lithotripsy (ESWL) could improve the efficacy of percutaneous nephrolithotomy (PCNL) for complicated renal calculi. Methods 160 cases of complicated renal calculi patients were divided into observation group (80) and control group (80) at random. Take conventional PCNL treatment for control group, and ESWL treatment one day before conventional PCNL treatment for observation group. Record the operation time, intraoperative blood loss, postoperative calculi clearance rate, complications, treatment costs, hospital stays of two groups of patients, then compare the curative effects between the two groups. Results Results are very different in the two groups, and the therapeutic effect of observation group is much better than control group (P < 0.05). Conclusions For complicated renal calculi, compared with conventional PCNL, in reducing the residual stone rate shorting the operation time, reducing the operation number, complications, treatment costs and the length of hospital stay, PCNL preoperative ESWL have obvious advantages. It is a kind of both economic and safe and effective treatment method.

The dynamic observation of plasma concentration of antimicrobial agents during balanced ultrafiltration in vitro / 中华胸心血管外科杂志

Objective Routine perioperative intravenous antimicrobial agents,was administered as surgical prophylaxis.However,whether balanced ultrafiltration during extracorporeal circulation can remove antimicrobial agent remains unclear.The concentrations of antimicrobial agent in plasma and ultrafiltrate samples were measured in this pseudo-extracorporeal circulation model.Methods Extracorporeal circulation consisted of cardiotomy reservoir (Ningbo Fly Medical Healthcare CO.,LTD.Ningbo,China),D902 Lilliput 2 membrane oxygenator (Sorin Group Asia Pte Ltd,Beijing,China) and Capiox (R) AF02 pediatric arterial line filter (Terumo Corporation,Beijing,China).HEMOCONCENTRATOR BC 20 plus (MAQUET Cardiopulmonary AG,Hirrlingen,Germany) was placed between arterial purge line and oxygenator venous reservoir.Fresh donor human whole blood was added into the circuit and mixed with Ringer's solution to obtain a final hematocrit of 24％-28 ％.After 30 minutes of extracorporeal circulation,zero-balanced ultrafiltration was initiated and arterial line pressure was maintained at approximately 100 mm Hg(1 mm Hg =0.133 kPa) with Hoffman clamp.The rate of ultrafiltration (12 ml/min) was controlled by ultrafiltrate outlet pressure.Identical volume of plasmaslyte A was dripped into the circuit to maintain stable hematocrit during 45 minutes of experiment.Plasma and ultrafiltrate samples were drawn every 5 minutes and concentrations of antimicrobial agent (including Cefmetasole and cefotiam) were measured with high performance liquid chromatography.Results All these two antimicrobial agents were detected in ultrafiltrate,demonstrating hemoconcentration may remove antimicrobial agent.The concentration of plasma antimicrobial agent decreased lineally with the increase of ultrafiltrate volume.At end of balanced ultrafiltration,the concentration of plasma cefotiam was (104.96 ± 44.36) μg/ml,which is about (44.38 ± 7.42) ％ of the initial concentration (238.95 ± 101.12) μg/ml; the concentration of plasma cefmetazole decreased linearly to (25.76 ± 14.78) μg/ml,which is about (49.69 ± 10.49) ％ of the initial concentration (51.49 ± 28.03) μg/ml.The total amount of cefotiam in ultrafiltrate is (27.16 ± 12.17)％ of the total dose administered,whereas cefmetasole in ultrafiltrate is (7.74 ±4.17)％.Conclusion Balanced ultrafiltration may remove antimicrobial agent from serum and has significant influence on plasma concentration of antimicrobial agent.The strategy of surgical prophylaxis should consider this unique technique during extracorporeal circulation.

Establishment and research progress of food pharmacy / 中国中药杂志

<p><b>OBJECTIVE</b>To introduce the establishment of food pharmacy research progress.</p><p><b>METHOD</b>To overview research situations of food pharmacy development according to edible product.</p><p><b>RESULT</b>Food pharmacy development in China has been set up preliminarily, and needs to be developed further.</p><p><b>CONCLUSION</b>The trend of the functional food will be safe, effective and its quality will be control.</p>

Effects of Saussurea Involucrata Culture on Mouse Immune Function / 中华中医药杂志

Objective:The tissue culture of Saussurea involucrata has been studied for the protection of immune function activities in animal models in our research.Methods: The tissue culture of S.involucrata at the doses of 75,150 and 300mg/kg were given to mice by intragastric administration,successive medication for 7 days,and then the effects of S.involucrata were investigated in mice by carbon clearance rate,DNCB induced delayed hypersensitivity and serum hemolysin formation.Results: The tissue culture of S.involucrata at the doses of 150mg/kg i.g.,for 7 days could inhibit the non-specificity of immune function in mice.At the doses of 300mg/kg i.g.,for 7 days it could have significantly inhibitory effect on delayed hypersensitivity in mice and increase the humoral immunity activity in mice.Conclusion: The tissue culture of S.involucrata had the protection effect on immune function activities.

Quantitative Evaluation on Adverse Drug Reaction Signal in FDA and Its Illumination / 中国药房

OBJECTIVE: To analyze and evaluate the quantitative evaluation of ADR signals in FDA and to provide a reference for ADR evaluation in China. METHODS: By means of literature review,contrasting analysis and data reduction,ADR signal evaluation in FDA was investigated. RESULTS&CONCLUSION: In USA MGPS method is used for the quantitative evaluation of ADR signal, which can earlier obtain ADR signal and effectively promote the risk warning ability of ADR information. This is practical in our country and we should learn from them. Combined with various data analyzing methods, we can set up a high-quality evaluation database for ADR signals. The importance of pharmacoepidemiology and statistics in ADR evaluation should be highly recognized and the methods for ADR signals evaluation should be gradually shifted from qualitative to quantitative evaluation.

Possible pharmacological mechanisms of endocannabinoids / 中国药理学通报

Endocannabinoids are endogenous brain ligands of cannabinoid receptors and have specific synthesizing,transporting,metabolizing ways in the body. Endocannabinoids can regulate release of some neurotransmitters such as glutamate or GABA. So elucidating the mechanism of endocannabinoids is not only helpful in understanding the mechanisms of cannabiod addicton but also useful in developing new useful drugs.

Effects of different kinds of opiate receptor on oxycodone-induced hyperlococomotor and analgesia in mice / 中国药理学通报

Aim To investage the effects of ?、?、?-receptor on hyperlocomotor and analgesia in mice.Methods Locomotor activity experiment and hot-plate pain experiment were measured.Results Oxycodone dose-dependently enhanced locomotor response in mice.Naloxone,a unselective opioid receptor antagonists and naltrindole(?-selective opioid receptor antagonist)could attenuate the increase of locomotor acitivity induced by oxycodone,but naloxonazine,a ?-receptor antagonist had no such effect.?-receptor antagonist nor-Binltorphimine increased hyperlocomotion induced by oxycodone.In antinociceptive experiment,naloxonazine and naltrindole could not attenuate the that of oxycodone,but nor-Binaltorphimine could attenuate the antinociceptive effects of oxycodone.Conclusion Oxycodone-hyperlocomotor is probably mediated by ? opioid receptor,and antinocieptive effects of oxycodone is probably mediated by ? opioid receptor.

Monitoring of Adverse Drug Reaction in Netherlands and Quantitative Evaluation on ADR Signal / 中国药房

OBJECTIVE:To provide reference for ADR evaluation in China.METHODS:The ADR signal evaluation method adopted by the pharmacovigilance center in Netherlands was analyzed by means of literature review,contrasting analysis and data reduction etc.RESULTS & CONCLUSION:We should draw experience from the pharmacovigilance center in Netherlands about the evaluation method on ADR signal and establish ADR evaluation databases of high quality;furthermore, we should attach great importance to the application of pharmacoepidemiology and statistics in ADR evaluation and gradually replace the qualitative evaluation with quantitative one for ADR signal.

Reviewing the Efficiency of Pharmacy Administration from the Perspective of Rational Use of Drugs / 中国药房

OBJECTIVE:To seek an effective starting point for the improvement of pharmacy administration efficiency(PAE)in China.METHODS:Level of PAE in China,the existing problems and their root causes were analyzed using a systematic methodology.RESULTS&CONCLUSIONS:Level of PAE in China is far from perfect,which may be attributed to the narrowly defined boundary of pharmacy administrating system,the lack of systematic understanding and command of relevant factors and the unscientific,non-integrated objective of pharmacy administration.It is advisable to enlarge system boundary,adjust the objective of pharmacy administration,and adopt a systematic point of view and methodology in the practice of pharmacy administration.

Analysis on Project Management in the New Drug Research&Development Process / 中国药房

OBJECTIVE:To probe into the practical importance of project management in the new drug Research&De-velopment.METHODS:The foreign project management in the new drug Research&Development was reviewed,the dif-ferences of which in the development of innovative drugs and the imitated drugs were analyzed.RESULTS&CONCLUSION:A complete,detailed and practical project program must be work out to enhance project management in the new drug Research&Development of China,an working group that of clear position&responsibility and high efficiency should be established,and a rigorous project monitoring should be carried out.

Effects of Resina Draconis on the Levels of Plasma Glucose, Insulin and Lipids in Rats / 中药新药与临床药理

Objective:To investigate the effects of Resina Draconis on the levels of plasma glucose,insulin and lipids in normal and diabetic rats. Methods: Hyperglycemia rat models were induced by glucose or adrenaline and rat models with diabetes mellitus were induced by alloxan.The levels of plasma glucose, insulin and lipids (triglyceride, total cholesterol and HDL-C) were determined. Results: Resina Draconis had no obvious effects in decreasing the plasma sugar level in normal fasted rats but could decrease the plasma sugar level and improve the glucose-resistance in glucose-induced or adrenaline-induced hyperglycemic rats and alloxan-induced fasted diabetic rats and increase insulin secretion in both normal and diabetic rats. It could also decrease the plasma lipid level in alloxan-induced diabetic rats. Conclusion: Resina Draconise exerts a good therapeutic effect on hyperglycemia in diabetic rats and its mechanism may be related to the increase of the secretion of insulin.

Effect of Tangmoning on nerve conduction velocity and RBC sorbitol level in diabetic rats / 中成药

AIM: To investigate the effects of Tangmoning (TMN) Granule on nerve conduction velocity, red blood cell sorbitol (RBC S) level in diabetic rats and probe the mechanism of prevention and treatment of diabetic peripheral neuropathy. METHODS: The model of diabetic rat was induced by strepotozotocin. The animals were randomly divided into six groups:TMN minimal dose group, TMN mild moderate dose group, TMN maximal dose group, methycobal group, model group and normal control group. All TMN groups were treated with TMN Granule through tube feeding (2.95 g/kg、5.90g/kg、11.80g/kg). Methycobal group was treated with methycobal tablets through tube feeding (0.14mg/kg). The duration of treatment was 3 weeks. The caudal nerve conduction velocity, RBC S content were investigated before and after treatment. RESULTS: It showed that TMN Granule could increase the caudal nerve conduction velocity significantly in the maximal dose group and the mild moderate dose gorup ( P

Research advances on signal transduction pathways as therapy targets in gastric cancer / 中国药理学通报

During the last forty years, although cytotoxic chemotherapy for gastric cancer patients has improved to some extent, its therapeutic effect is limited. Simultaneously, great progression of oncobiology to increase our understanding of the molecular basis of gastric cancer has been made. Currently the cancer cell has been characterized by several genetic changes that lead to altered cellular functions. In addition, multiple cancer-cell environment factors affect the tumor cell via various receptors and subsequent signaling pathways. The increasing knowledge of cellular signaling offers the opportunity to develop novel substances that target specific pathway molecules.