Research progress in psychopharmacology based on approach-avoidance conflict behavior / 中国药理学与毒理学杂志

Approach-avoidance conflict(AAC)refers to the internal conflict that individuals experi-ence when faced with conflicting approach or avoidance thoughts.It reveals some characteristics of mental disorders,such as anxiety,depression,and addiction represented by excessive tendencies of approach or avoidance.The function of the cortico-limbic-striatal system influences behavioral choices at the neural level during the onset of AAC,and the development of related behavioral paradigms that can better represent AAC behaviors is critical to evaluating the efficacy of drugs and guiding the development of new drugs.This paper summarizes the neural mechanisms,behavioral paradigms,and applications in behavioral pharmacology related to AAC behaviors from the perspective of psychopharmacology with a view to providing new perspectives and methods for the diagnosis and treatment of related neuro-psychiatric disorders.

Effect of buspirone and mianserine on anxiety-and depression-like behaviors induced by Liang′s contextual-stress box in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of anxiolytics and antidepressants on anxiety-and/or depression-like behaviours induced by designing a Liang′s contextual-stress box, (Liang′s box) in mice . METHODS Liang′s box was composed of a central area and three peripheral arms. Buspirone (0.5 and 1.0 mg·kg-1) and mianserin (0.25 and 0.5 mg·kg-1) were injected to mice intraperitoneally and the following behavioral indexes were recorded: ① latency to the central area(CA), ② CA-time, ③ CA-distance,④distance traveled in the peripheral area (PA-distance)⑤number of the transitions, and ⑥global activity. RESULTS ①Buspirone 0.5 and 1.0 mg · kg-1 decreased the latency to CA by as much as 71.9%(P<0.05) and 77.9%(P<0.05), but dose-dependently increased the CA-time by 59.5% and 73.8%(P<0.05) respectively. Although buspirone 0.5 and 1.0 mg · kg-1 obviously reduced the shuttle number(P<0.05), it did not have significant pharmacological effects on the CA-and PA-distance or global activity.②Mianserin 0.25 and 0.5mg·kg-1 decreased the latency to CA by as much as 72.4%(P<0.05) and 82.3%(P<0.05), but dose-dependently increased the CA-time by 39.1%and 43.9%(P<0.05), respec?tively. Mianserin enhanced the shuttle number(P<0.05) and CA-distance(P<0.05) in a dose-dependent manner, but it had no obvious pharmacological effects on the PA-distance or global activity. CONCLUSION Anxiety-and/or depression-like behaviors can be stimulated by Liang′s box in mice, which may be used as a novel animal model of anxiety and depression comorbidity to study its pathophysiological mecha?nisms, screen and evaluate certain new anxiolytics and antidepressants.

Research progress on therapeutic agents for alcohol dependence syndrome / 中国药理学通报

Alcohol is widely abused in contemporary social life, which has become a serious medical and social problem because it hurts human health and endangers public safety. Recent re-search has developed several active substances that can effective-ly improve or treat this syndrome via affecting the mesolimbic do-pamine nervous pathway to dampen rewarding effectiveness in-duced by ethanol. This paper reviews the progress in near-term studies of alcoholism-intervening agents, aiming at providing ref-erences for related mechanism exploration and drug development.

Research progress of PDE4 in the central nervous system / 中国药理学通报

Phosphodiesterase-4 ( PDE4 ) has been one of the most popular drug targets during recent years due to its critical role in the control of intracellular cyclic adenosine monophos-phate ( cAMP ) concentration and downstream signal transduc-tion. PDE4 is widely distributed in the central nervous system ( CNS) with different expression levels of its four subtypes. Re-cent data indicate that altered PDE4 expression and/or activity is relevant to multiple CNS disorders, such as depression, memory deficiency, drug dependence, and neural lesion. Selective PDE4 inhibitors exhibit therapeutic effects on these disorders and might be a promising pharmacotherapy. The paper highlights recent re-search progress in the roles of PDE4 in CNS function, and dis-cusses the prospects of PDE4 as a novel therapeutic target for CNS disorders.

Tissue reaction and injury after nitinol artificial esophagus replacement / 中国组织工程研究

BACKGROUND:Previous experiment has confirmed that the nitinol artificial esophagus is an artificial succedaneum which can be used for replacing an esophagus resected and rebuilding esophageal tube. OBJECTIVE:To observe the tissue reaction of the neo-esophagus and the adjacent organs injury contacted with the nitinol artificial esophagus after replacement. METHODS:Eight miniature pigs were selected and modeled by resection of a 70 mm segment of the thoracic esophagus. After modeling, the nitinol artificial esophagus was inserted into the proximal and distal end of the thoracic esophagus at an insert distance of about 10 mm. After that, the nitinol artificial esophagus with polyester connecting ring was sewed into the thoracic esophagus in a manner of ful-thickness anastomosis. After operation, the pigs were subjected to feeding regulation measures to control the shedding time of the artificial esophagus. Two model pigs were sacrificed for anatomical observation at 1, 2, 3, 4 months postoperatively, respectively. The tissue reaction during the neo-esophagus formed procedure and adjacent organs injury contacted with the nitinol artificial esophagus were observed. RESULTS AND CONCLUSION:Al pigs survived without complications such as thoracic hemorrhage, pneumothorax, pyothorax, esophageal perforation and anastomotic leakage. The experimental animals with the nitinol artificial esophagus fixed in situ had no dysphagia for eating semisolids food (Bown’SⅡ). Autopsy findings showed that there was slight membrane-like adhesion between partial pleura and lung. No hydrothorax was found. The nitinol artificial esophagus was wrapped up by the neo-esophagus. There was slight membrane-like adhesion between the neo-esophagus and the adjacent organs such as the lung, aorta and esophageal mucosa. The esophageal mucosa covered the neo-esophageal entocoele from esophageal stumps to intermedius of neo-esophagus until completely covered. Histological findings of the neo-esophagus showed that in imbed cycle of the nitinol artificial esophagus the tissue reaction showed aseprtic inflammation reaction and foreign body reaction around the implant. These tissue reactions were most severe at 1 month after operation and thereafter relieved gradual y.

Application of artificial prosthesis constructed by titanium-nickel alloy and silicone in repairing esophageal defects / 中国组织工程研究

BACKGROUND: The stomach is usually used to substitute the diseased esophagus, which will change the physical digestive passage and results in some complications, such as back-streaming, poor food intake, and dyspepsia. If there is an artificial esophagus to replace the diseased esophagus, then the complications would be greatly reduced, and surgical procedures would be simplified. OBJECTIVE: To investigate the effects of artificial prosthesis of titanium-nickel alloy and silicone on repairing esophageal defect after part excision of esophagus. DESIGN, TIME AND SETTING: An in vivo observation experiment based on animals was performed at the animal laboratory of Second Affiliated Hospital of Guangzhou Medical College between May 1999 and May 2001. MATERIALS: Sixteen pigs of either gender, weighting 30 35 kg, were included. The artificial esophagus constructed by titanium-nickel alloy and silicone were provided by General Research Institute for Nonferrous Metals. Its length was 10 cm and its internal diameter was 20 mm. Its inner layer was made of silicone and its outer layer was titanium-nickel alloy net. METHODS: A segment of 7-cm thoracic esophagus was resected and was replaced by an artificial prosthesis constructed by titanium-nickel alloy and silicone. At 1, 2, 3, 4, 5, 6, 7, and 8 weeks, as well as 3, 4, 6, 8, 10, and 12 months after surgery, animals were sacrificed to take specimens. Sedal slices were stained by hematoxylin-eosin for pathological examination. MAIN OUTCOME MEASURES: Autopsy and histopathological findings of neo-esophagus. RESULTS: Of initial 16 pigs, 1 died owing to shock caused by hemorrhee, 1 died of excessive anesthesia, and the remaining 14 pigs survived a period from 7 days to 1 year. Following sacrifice, some vomicas containing yellow and white liquor purls on the chest wall of 4 pigs were observed, which were wrapped but did not communicate the thoracic cavity. One artificial esophagus was not in place but found in the stomach. One artificial esophagus was twisted and formed an esophagus diverticulum. The false passage around the prosthesis formed so long as the animals survived more than 1 week, which was called as neo-esophagus. The neo-esophagus was constructed primadly by granulation tissue within approximately 2 weeks, and then fibrous connective tissue replaced it. Four weeks later, esophageal epithelial cells covered the internal cavity of the "nee-esophagus". At this time, neonatal smooth muscle cells could be observed, but gland regeneration was not found. Following artificial esophagus displacement, the middle segment of "neo-esophagus" presented with stenosis to different degrees. The stenosis segment tended to stabilize with time (approximately 6 months later). CONCLUSION: Esophageal defect within a certain range of length can be repaired by an artificial esophagus constructed by titanium-nickel alloy and silicone.

Quantification of IL-10 gene expression in induced sputum of asthmatic patients by competitive PCR / 医学研究生学报

Objective: To investigate the role of anti-inflammatory cytokine IL-10 in the pathogenesis of asthma.Methods:IL-10 internal standards was constructed by restriction digest.The expression levels of IL-10 mRNA were determined in peripheral blood and induced sputum of 23 asthmatic patients by(RT-PCR) with this competitive internal standards. Results:There was no IL-10 mRNA expression in most of the asthmatics.IL-10 mRNA was detected in some catabatic patients.But IL-10 mRNA was readily detected in 29 normal subjects. Conclusion:Airway inflammation of asthma was related to the expression of IL-10 gene.Asthmatic patients may have difficulty in IL-10 synthesis with transcript.

Psychoactive substances and DNA methylation / 中国药理学通报

Psychoactive substances abusing may induce neuron-specific adaptation and lead to physical and psychological dependence.Moreover,psychoactive substances have toxicological actions to cause physical damages.It has been reported that DNA methylation,acting as an epigenetic modification,may be one of the mechanisms involved in these adaptive changes and physical damages.This review shows a general introduction to the molecular mechanism of DNA methylation,and expounds the pharmacological and toxicological effects of some psychoactive substances on DNA methylation,including ethanol,methamphetamine,morphine,and cocaine.

Role of behavioral sensitization animal model in evaluation of drug dependence / 中国药理学通报

Drug abuse and addiction are increasingly severe, which is both a serious social problem and an important medical research work. It is very significant to evaluate dependence potential of centrally acting drugs. Several lines of evidence have shown that there is a close relationship between drug sensitization and drug abuse and addiction. More attention has been directed to sensitization of abused drugs. We introduce the establishment of behavioral sensitization animal model, review neurobiological mechanisms underlying development and expression of behavioral sensitization, and further discuss the role of behavioral sensitization animal model in evaluation of drug dependence.

Effects of L-type calcium channel blockers on tramadol-induced analgesia in mice / 中国药理学通报

Aim To investigate the effects of L-type calcium channel blockers on tramadol-induced analgesia.Methods Hot-plate test and writhing test were used to measure the analgesia induced by tramadol. Verapamil, nimodipine or nifedipine was co-administrated with tramadol to determine its effects on tramadol analgesia.Results Tramadol (10, 20, 40 mg?kg -1 in hot-plate test or 2, 5,10 mg?kg -1 in writhing test) produced significantly analgesia in hot-plate test and writhing test. Co-administration of verapamil and tramadol prolonged the latency of pain response of mice in hot-plate test.In writhing test, verapamil, nimodipine and nifedipine could potentiate the analgesic effect of tramadol in a dose-dependent manner.Conclusion L-type calcium channel blockers can potentiate tramadol-induced analgesia. Calcium influx mediated by L-type calcium channels may be involved in tramadol-induced analgesia.

The investigation on the microvessel density and lymphonode micrometastasis as the supplement parameter of TNM stages in esophageal cancer / 中国医师杂志

0.05).Conclusion The MVD and micrometastasis of regional lymph nodes,which act as the supplement parameter of TNM stages of esophageal cancer for T and N factors,are the important prognosis factors for esophageal cancer.

Progress in brain-derived interleukins / 中国药理学通报

It is traditionally thought that interleukins are produced by immunocytes. However, abundant evidence indicates that neuron and neuroglia also produce and excrete interleukins. Brain derived interleukins have reciprocal action with multiple neurotransmitters, and influence animal's behavior, learning and memory. Moreover, brain derived interleukins are involved in Alzheimers disease, depression and so on. Further investigation on brain derived interleukins may improve in understanding the pathophysiology of some related diseases.

The progress in the mechanisms of methamphetamine neurotoxicity / 中国药理学通报

Research into methamphetamine-induced neurotoxicity has experienced a resurgence in recent years. This is due to an increased abuse of the substance internationally. The long-term abuse of methamphetamine will result in neurochemical, neuropathological and behavioral changes. Recent data implicate that dopamine oxidation, glutamate-induced excitotoxicity, disruption of mitochondria, and apoptosis are involved in the injury of methamphetamine to central nervous system. Further, Involvement of cell death-related genes in the neurotoxic effects of methamphetamine is also discussed.

Trifluoperazine attenuates naloxone-precipitated symptoms in morphine-dependent rats and mice / 中国药理学通报

AIM To investigate the effects of trifluoperazine on naloxone precipitated withdrawal symptoms in morphine dependent rats and mice, and its pharmacological mechanisms. METHODS\ Naloxone precipitated tests in morphine dependent rats and mice were used. RESULTS\ Trifluoperazine(2～20 mg?kg -1 ) dose dependently inhibited naloxone precipitated withdrawal jumping, wet dog shakes, paw tremor and weight loss in morphine dependent mice. With ip trifluoperazine (5～20 mg?kg -1 ), most of positive withdrawal symptoms, including jumping, wet dog shakes, defeacation, weight loss, teeth chattering, salivation, diarrhea, ptosis and irritating, induced by naloxone in morphine dependent rats were significantly reduced. Apomorphine (2～8 mg?kg -1 ), a mixed DA 1/DA 2 receptor agonist, did not affect inhibition of trifluoperazine on naloxone precipitated withdrawal symptoms in morphine dependent mice. However, nifedipine(5～20 mg?kg -1 ), a L type voltage sensitive calcium channel blocker, enhanced a pharmacological action of trifluoperazine against naloxone precipitated symptoms in morphine dependent mice. CONCLUSION\ Trifluoperazine attenuates naloxone precipitated withdrawal symptoms in morphine dependent rats and mice by inhibiting the activity of post receptor calmodulin, but it does not antagonizes DA 2 receptor, in central nervous system.

A lungs-specific liposomal delivery system for gene therapy / 中国免疫学杂志

Objective:To construct and evaluate a Salmeterol lungs-specific liposomal delivery system.Methods:①Liposome were prepared by the reverse-phase evaporation method and instilled into the tracheas of SD strain rats.The influence of Salmeterol on the uptakes of liposome was evaluated.②pEGFPC1(25 ?g/rodent) encapsulated in lungs-specific liposome were administered intravenously into Guinea pigs,GFP expression were observed by means of fluorescent microscopy 24h and 48h after administration.Results:①2,4,8,12,16 hours after instillation,lungs-specific liposome uptake were significantly higher than nonspecific liposome uptake(P