Agmatine ; administration & dosage ; pharmacology ; Analgesia ; methods ; Animals ; Injections, Spinal ; Male ; Morphine ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects

Human rhinoviruses (HRVs) are the causative pathogens in more than half of viral upper respiratory tract infections. Currently, no antiviral agents that are active against HRVs are available for clinical use. Because only higher primates are susceptible to HRVs, the screening of new drug is most commonly based on the cell line model. In this study, isolated rabbit airway smooth muscles (ASM) tissue model has been established, and the airway responsiveness with different treatment has been examined. Relative to control tissues, the maximal constrictor (Tmax) response to ACh increased significantly 150% in ASM inoculated with HRV, and relaxation to isoproterenol has been attenuated to 63%. And the abnormal responsiveness can be inhibited in presence of pretreatment with several new compounds which have been exhibited effective anti-HRV activity on cell lines. The results demonstrate that the established ASM model will be applied to screening the anti-HRVs drugs.
Acetylcholine ; pharmacology ; Animals ; Antiviral Agents ; pharmacology ; Cytopathogenic Effect, Viral ; drug effects ; HeLa Cells ; Humans ; Isoproterenol ; pharmacology ; Muscle Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Muscle, Smooth ; drug effects ; physiopathology ; virology ; Piperidines ; pharmacology ; Pyridazines ; pharmacology ; Rabbits ; Rhinovirus ; Trachea ; drug effects ; physiopathology ; virology

Thienorphine is a chemically-new opioid developed in Beijing Institute of Pharmacology and Toxicology. To elucidate the chemical basis for the unique pharmacological effects of thienorphine, 15 derivatives were synthesized according to combinatorial chemistry and the structure-activity relationships of these compounds were studied. It is demonstrated that thienorphine is a potent long-acting partial agonist. N-Cyclopropylmethyl is responsible for the antagonist effect of thienorphine. More importantly, thiophene at the end of side chain is most likely the pharmacophore accounts for the long-lasting effect of thienorphine. Change of the connection of thiophene and the side chain does not result in changes in the antinociceptive activity.
Animals ; Buprenorphine ; analogs & derivatives ; pharmacokinetics ; pharmacology ; Combinatorial Chemistry Techniques ; Dose-Response Relationship, Drug ; Female ; Male ; Mice ; Mice, Inbred Strains ; Morphine ; pharmacology ; Rats ; Rats, Wistar ; Receptors, Opioid ; agonists ; Structure-Activity Relationship

AIM:To compare the clinical effect of 23G and 25G+ vitrectomy for treatment of proliferative diabetic retinopathy (PDR).METHODS: A total of 128 PDR patients (195 eyes) requiring vitrectomy in our hospital from November 2013 to May 2016 were randomly divided into 25G+ group and 23G group, 64 cases (97 eyes) in 25G+ group and 64 cases (98 eyes) in 23G group.In 25G+ group, patients were treated by 25G+ vitrectomy.In 23G group, patients were treated by 23G vitrectomy.The visual acuity, as well as intraocular pressure (IOP), iatrogenic injury and complications in two groups were recorded before and 1d, 1wk, 1mo after treatment.The operation time was compared between two groups.RESULTS: The operation time in 25G+ group was lower than that in 23G group (P<0.05).The postoperative visual acuity at 1mo of two groups were improved compared with before surgery (P<0.01).However, visual acuity between two groups in the same period had no significant difference (P>0.05).IOP in 25G+ group before surgery had no significant difference compared with those after surgery at 1d,1wk, and 1mo(P>0.05), which it was the same in 23G group.IOP of two groups in the same period had no significant difference (P>0.05).The incidence rate of iatrogenic injury in 25G+ group was 4.1%, which was significant lower than that of 23G group (13.3%) (P<0.05).The incidence rate of complication in 25G+ group was 3.1%, which was significant lower than that of 23G group (11.2%) (P<0.05).CONCLUSION: Both 23G and 25G+ vitrectomy are safe and effective treatment for PDR.However, 25G+ vitrectomy is the better choice for PDR for the shorter operation time, lower incidence rate of iatrogenic injury and fewer surgical complications.

Schizophrenia, described as the worst disease affecting mankind, is a severe and disabling mental disorder. Schizophrenia is characterized by complicated symptoms and still lacks a diagnostic neuropathology, so developing schizophrenia animal models which have quantifiable measures tested in a similar fashion in both humans and animals will play a key role in new therapeutic approaches. According to the symptoms of cognitive impairment and emotional disorder, the N-methyl-d-aspartate (NMDA)-receptor antagonist MK-801 was applied to induce schizophrenia-like behavior in mice. Locomotor activity and prepulse inhibition (PPI) were selected as indices and the effect of clozapine was also investigated in this model. The results showed that compared with the normal group, MK-801-treated mice exhibited significantly increased locomotor activity and impaired PPI, and pre-exposure to clozapine could ameliorate the abnormality and make it back to normal level. These findings suggest that the model we established could be a useful tool for antipsychotic drug screening.
Animals ; Antipsychotic Agents ; pharmacology ; Clozapine ; pharmacology ; Disease Models, Animal ; Dizocilpine Maleate ; Inhibition (Psychology) ; Male ; Mice ; Motor Activity ; drug effects ; Receptors, N-Methyl-D-Aspartate ; antagonists & inhibitors ; Schizophrenia ; chemically induced ; physiopathology

In order to investigate the role of spinal glutamate transporter 1 (GLT-1) in the neuropathic pain and morphine tolerance, rat chronic constriction injury (CCI) of sciatic nerve was performed, and the mechanical allodynia was evaluated by mechanical withdrawal threshold (MWT), the expression of GLT-1 was measured by real-time PCR and Western blotting analysis. The results showed that compared to sham group, the MWT of CCI group had decreased approximately 80%. Administration of morphine alone could develop tolerance rapidly in initial two days, and then had no significant difference with CCI group, the expression of GLT-1 was down-regulated. Ceftriaxone sodium alone could improve mechanical allodynia. Co-administration of ceftriaxone sodium with morphine attenuated morphine tolerance and up-regulated GLT-1 expression, and the MWT remained at high level after 6 days. In conclusion, change of spinal GLT-1 expression and function has close correlation with the development of neuropathic pain and morphine tolerance.
Animals ; Drug Tolerance ; Excitatory Amino Acid Transporter 2 ; metabolism ; pharmacology ; Female ; Male ; Morphine ; pharmacology ; Radiculopathy ; metabolism ; pathology ; Rats ; Rats, Wistar ; Sciatic Nerve ; pathology ; Sciatic Neuropathy ; metabolism ; pathology ; Spinal Cord ; drug effects ; metabolism

OBJECTIVETo investigate the use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy.

METHODSFrom April 2008 to March 2010, anterior cervical discectomy and fusion with self-locking cages were performed on 45 patients who suffered from multi-segmental cervical myelopathy, among of them there were 23 male and 22 female, aged from 32 to 67 years (average 53 years). Recording the Japanese Orthopedic Association (JOA) scores and SF-36 scores in the protocol time point, in order to investigate the clinical outcome, meanwhile, accumulating the pre-operation and postoperation X-ray films of cervical spine for measuring the height of intervertebral space, whole curvature of cervical spine and the rate of fusion by repeated measures analysis of variance.

RESULTSThe mean follow-up time was 28.4 months (24 - 35 months). JOA scores ascended from preoperative 6.5 ± 3.1 to postoperative 13.4 ± 1.7 (F = 17.84, P = 0.001), the 7 scores of SF-36 improved significantly after operation (t = 1.151 - 12.207, P < 0.05), but mental health not. The fineness rate was 91.1%. Height of disc space ascended from preoperative (5.5 ± 1.8) mm to postoperative (8.3 ± 0.8) mm (F = 11.71, P = 0.043), globle curvature of cervical spine ascended from preoperative 5° ± 7° to postoperative 10° ± 14° (F = 234.53, P = 0.000), the change of the two index was significantly, respectively. Fat necrosis in one case and hematoma in another case at the bone donor-site were found, both of the two cases were cured by physiotherapy. All of the 45 cases (111 segments) achieved bone fusion.

CONCLUSIONThe use of anterior cervical discectomy and fusion with self-locking cages to treat multi-segmental cervical myelopathy possess many advantages as follows: satisfactory clinical outcome, minimally invasive, higher fusion rate, higher orthopaedic ability.

Adult ; Aged ; Cervical Vertebrae ; surgery ; Decompression, Surgical ; methods ; Diskectomy ; methods ; Female ; Follow-Up Studies ; Humans ; Internal Fixators ; Male ; Middle Aged ; Spinal Cord Diseases ; surgery ; Spinal Fusion ; instrumentation ; methods ; Treatment Outcome

Objective:To observe the effects of electroacupuncture (EA) of three different frequencies (2 Hz,80 Hz and 2 Hz/80 Hz) on the free radicals in hippocampus of vascular dementia (VD) model mice.Methods:A total of 100 Kunming mice were randomly divided into a sham operation group,a model group,a 2 Hz EA group,an 80 Hz EA group and a 2 Hz/80 Hz EA group,with 20 mice in each group.The ischemia-reperfusion VD model was established by repeated blockade of bilateral common carotid arteries.Mice in EA groups began EA treatment on the 4th day after the operation.Baihui (GV 20),Dazhui (GV 14),Geshu (BL 17) and Zusanli (ST 36) were punctured and then connected to EA instrument,with different waves of 2 Hz,80 Hz or 2 Hz/80 Hz (10 min/time) applied accordingly,once a day.During the jumping stand experiment,the learning performance,memory performance and hippocampal calcitonin gene-related peptide (CGRP),nitric oxide synthase (NOS),malondialdehyde (MDA),changes in superoxide dismutase (SOD) and true choline esterase (TChE) were observed.In hippocampus,the CGRP level was determined by radioimmunoassay;the MDA level was determined by thiobarbituric acid colorimetric method;the activities of NOS and TChE were determined by spectrophotometry;the activity of SOD was determined by xanthine oxidase method.Results:Compared with the sham operation group,the performances of learning and memory decreased significantly in the model group (P＜0.01);in hippocampus,the CGRP level decreased,the MDA level increased,the activities of NOS and TChE increased,and the activity of SOD decreased in the model group.Compared with the model group,the learning and memory performances of the EA groups were significantly improved (P＜0.05 or P＜0.01);in hippocampus,the CGRP level increased,the MDA level decreased,the NOS and TChE activities decreased,and the SOD activity increased (P＜0.05 or P＜0.01).Among EA groups,the 2 Hz/80 Hz EA group was superior to the 2 Hz EA group and the 80 Hz EA group (P＜0.05 or P＜0.01).Conclusion:EA can improve the cognitive impairment of mice with ischemia-reperfusion VD.The mechanism may be related to the improvement of cerebral blood circulation,regulation of the central neurotransmitters,fighting lipid peroxidation and promoting nerve cell repair.The therapeutic effects of EA with different frequencies were different,and the intervention effect by EA at 2 Hz/80Hz is the most significant.

Death, Sudden ; epidemiology ; Emergency Service, Hospital ; statistics & numerical data ; Humans

OBJECTIVETo investigate the role of lung resistance-related protein (LRP) in intrinsic multidrug resistance (MDR) of bladder cancer and detect the relationship of LRP expression with the clinical pathologic parameters.

METHODS66 patients were studied with newly diagnosed primary bladder cancer (T(a) = 12, T(1) = 26, T(2) = 11, T(3) = 10, T(4) = 7; G(1) = 35, G(2) = 19, G(3) = 12). No patient was treated preoperatively with either radiation or chemotherapy. Reverse transcription-polymerase chain reaction (RT-PCR) was performed for measure of mRNA expression for LRP, multidrug-resistance gene 1 (MDR1), and multidrug resist nce-associated protein 1 (MRP1). Expressions of LRP, P53 and P63 proteins were examined by immunohistochemistry staining.

RESULTSLRP mRNA had the highest expression rate (64%, 42/66) among three MDR markers in primary bladder cancers without chemotherapy and its level was significantly higher in normal bladder tissue than in TCC of bladder (t = 2.82, P < 0.01), in low grade than in high grade cancers (t = 4.14, P < 0.01), and in superficial than in invasive cancers (t = 3.58, P < 0.05). LRP mRNA expression showed no correlation with either MDR1 or MRP1, but close correlation with LRP protein level (r = 0.89, P < 0.01). LRP was associated with low-grade (r = 0.81, P < 0.01) and low-stage (r = 0.78, P < 0.05) cancers, but not with tumor suppressor P53 or P63 (P > 0.05).

CONCLUSIONSThe grade and stage-related expression pattern of LRP indicates that it may be a predictive index for intrinsic MDR in bladder cancer. Anti-cancer drugs out of the MDR spectrum of LRP may be more effective for patients with early bladder cancer.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adult ; Aged ; Carcinoma, Transitional Cell ; genetics ; metabolism ; pathology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Female ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; biosynthesis ; genetics ; Neoplasm Proteins ; biosynthesis ; genetics ; RNA, Messenger ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Urinary Bladder Neoplasms ; genetics ; metabolism ; pathology ; Vault Ribonucleoprotein Particles ; biosynthesis ; genetics