Structure-activity relationship of pyrazol-4-yl-pyridine derivatives and identification of a radiofluorinated probe for imaging the muscarinic acetylcholine receptor M4

There is an accumulating body of evidence implicating the muscarinic acetylcholine receptor 4 (M4) in schizophrenia and dementia with Lewy bodies, however, a clinically validated M4 positron emission tomography (PET) radioligand is currently lacking. As such, the aim of this study was to develop a suitable M4 PET ligand that allows the non-invasive visualization of M4 in the brain. Structure-activity relationship studies of pyrazol-4-yl-pyridine derivates led to the discovery of target compound 12 - a subtype-selective positive allosteric modulator (PAM). The radiofluorinated analogue, [18F] 12, was synthesized in 28 ± 10% radiochemical yield, >37 GBq/μmol and an excellent radiochemical purity >99%. Initial in vitro autoradiograms on rodent brain sections were performed in the absence of carbachol and showed moderate specificity as well as a low selectivity of [18F] 12 for the M4-rich striatum. However, in the presence of carbachol, a significant increase in tracer binding was observed in the rat striatum, which was reduced by >60% under blocking conditions, thus indicating that orthosteric ligand interaction is required for efficient binding of [18F] 12 to the allosteric site. Remarkably, however, the presence of carbachol was not required for high specific binding in the non-human primate (NHP) and human striatum, and did not further improve the specificity and selectivity of [18F] 12 in higher species. These results pointed towards significant species-differences and paved the way for a preliminary PET study in NHP, where peak brain uptake of [18F] 12 was found in the putamen and temporal cortex. In conclusion, we report on the identification and preclinical development of the first radiofluorinated M4 PET radioligand with promising attributes. The availability of a clinically validated M4 PET radioligand harbors potential to facilitate drug development and provide a useful diagnostic tool for non-invasive imaging.

Simultaneous Determination of Liquiritin and Glycyrrhizic Acid in Wuwei Shaji Granules by HPLC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of liquiritin and glycyrrhizic acid in Wuwei shaji granules.METHODS:HPLC method was adopted.The determination was performed on Thermo scientific ODS-2 Hypersil column with mobile phase consisted of acetonitrile-0.5％ phosphoric acid (gradient elution) with flow rate of 1.0 mL/min.The detection wavelength was set at 237 nm,and column temperature was 25 ℃.The sample size was 20 μL.RESULTS:The linear ranges of liquiritin and glycyrrhizic acid were 48-480 μg(r=0.999 9) and 90-900 μg(r=0.999 9),respectively.The limits of quantitation were 0.55,2.10 μg/mL,and the limits of detection were 0.16,0.62 μg/mL.RSDs of precision,stability and reproducibility tests were all lower than 2.0％.The recoveries were 95.08％-97.58％ (RSD=0.93％,n=6)and 95.86％-99.89％ (RSD=1.67％,n=6),respectively.CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for the content determination of liquiritin and glycyrrhizic acid in Wuwei shaji granules.

Simultaneous Determination of Liquiritin and Glycyrrhizic Acid in Wuwei Shaji Granules by HPLC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of liquiritin and glycyrrhizic acid in Wuwei shaji granules.METHODS:HPLC method was adopted.The determination was performed on Thermo scientific ODS-2 Hypersil column with mobile phase consisted of acetonitrile-0.5％ phosphoric acid (gradient elution) with flow rate of 1.0 mL/min.The detection wavelength was set at 237 nm,and column temperature was 25 ℃.The sample size was 20 μL.RESULTS:The linear ranges of liquiritin and glycyrrhizic acid were 48-480 μg(r=0.999 9) and 90-900 μg(r=0.999 9),respectively.The limits of quantitation were 0.55,2.10 μg/mL,and the limits of detection were 0.16,0.62 μg/mL.RSDs of precision,stability and reproducibility tests were all lower than 2.0％.The recoveries were 95.08％-97.58％ (RSD=0.93％,n=6)and 95.86％-99.89％ (RSD=1.67％,n=6),respectively.CONCLUSIONS:The method is simple,accurate and reproducible,and can be used for the content determination of liquiritin and glycyrrhizic acid in Wuwei shaji granules.

Clinical application of different implant materials in total hip arthroplasty / 中国组织工程研究

BACKGROUND:Early clinical application of non-biological materials (bone cement) for treatment of hip joint is ineffective, due to the large fixed range, long fixation time, as wel as aging and rupture of bone cement interface causing complications such as prosthetic loosening. Thus, postoperative range of motion of the hip joint can be affected to some degree. OBJECTIVE:To investigate the methods and progress of biological and non-biological materials for total hip replacement and to assess the features and clinical application of different hip prostheses. METHODS:A computer-based search of PubMed and CNKI was performed by the first author to retrieve articles related to biological materials and tissue-engineered hip joint using the keywords of“carpal bone, fracture ununited”in the title and abstract. The keywords were limited to Chinese and English. RESULTS AND CONCLUSION:Biological materials for internal fixation have good wear resistance, corrosion resistance and biocompatibility. Currently, the combination of metal joint head and polyethylene acetabulum with ultrahigh molecular weight is the most commonly used in hip replacement. However, the metal joint head exhibits an elastic modulus far from the human skeleton, resulting in stress shielding effects which are easy to cause prosthetic loosening and instability. Bio-inert ceramics has high in vivo stability and good mechanical strength;and bioactive ceramics has bone conduction characteristics and performance of the living bone integration. Composite prosthesis, because of adjustable elastic modulus and sufficient mechanical strength, shows the mechanical properties close to the human bone and has been gradual y noticed. However, there is a lack of ideal prostheses with good biocompatibility and biomechanics. Therefore, hip design and manufacturing processes should be improved to elevate wear resistance and mechanical properties, to enhance the binding between prosthesis and the host bone, and to reduce stress shielding in order to improve the biocompatibility of the implant with the host, and extend the prosthetic life.

The influence of autoblood cardioplegia on ATPase in neonatus / 中国综合临床

Objective To study the influence of autoblood cardioplegia on ATPase in neonatus myocardium with congenital heart disease and approach the mechanism of self-blood cardioplegia in protecting the myocardium in neonatus.Methods There were 30 cases of neonatus with congenital heart disease with body weight less than 8 kg,including 2 cases of ventricular septal defect(VSD),11 of VSD with severe pulmonary hypertension(PH),9 cases of USD with ASD,2 cases of atrial septal defect (ASD),6 of VSD and FPO.30 neonatus were divided into autoblood cardioplegic solution group(group A,n=10),allograft blood cardioplegic solution group (group B,n=10)and crystalloid cardioplegic solution group(group C,n=10).The biopsies were taken from right atrium just before arrested and after heart self-recovery to measure ATPase.Results Comparing with preoperative one,Na+-K+-ATPase creased obviously after operation in group A,B ,C (P＜0.05 ).There had no significant difference among the three groups before operation (P＞0.05).After operation,myocardial cell's Na+-K+-ATPase,Ca2+-ATPase and Ca2+Mg2+-ATPase in group A were decreased obviously as compared with that in group B and C (P＜0.05).Conclusion There is slight influence of autobloed cardioplegia on ATPase in neonatus with congenital heart disease,which can give a good protection to the myocardium in neonatus.

Establishment of Focal Cerebral Ischemia Model with Modified Suture-occluded Method in Period of Rehabilitation and Analysis for Death Cause / 中国康复理论与实践

@#Objective To compare the reliability of modificatory method and traditional method in preparing ischemic stroke rat model in rehabilitation period.Methods 173 female SD rats were divided into traditional method group(n=63),modificatory method group(n=109) and control group(n=37).In the traditional method group,the thread embolus was inserted through the left external carotid artery(ECA),and then left ECA and pterygopalatine artery(PPA) were ligated.In the modificatory method group,the thread embolus was inserted through the left internal carotid artery(ICA) and only left common carotid artery(CCA) was ligated.In the control group,the thread embolus was not inserted,only CCA was ligated.Results There was no significant difference in neurofunction score between the modificatory method group and the traditional method group(P>0.05).The operating time was significantly shortened(P<0.01) and the survival time was significantly prolonged in the modificatory method group compared with that of the traditional method group(P<0.01).The two-month survival rate was 54.13% in the modificatory method group and 31.75% in the traditional method group receptively,the former was significantly longer than the latter(P<0.01).Conclusion The ischemic stroke model established by modificatory methods is not only precisely and reliable but also save operating time and improve survival rate of the animals compared with the traditional method.The main death causes of animals are large-area cerebral edema and electrolyte imbalance after operation.

Rehabilitation for Complications and Secondary Disturbance of Traumatic Brain Injury / 中国康复理论与实践

@#The rehabilitation and nursing for the complication and secondary disturbance are the important partition of treatment for patients with traumatic brain injury(TBI).Understanding the category,mechanism,prevention and treatment of complications can efficaciously decrease the incidence rate of them,relieve the distress of patients,increase the ablity of ADL and the quality of life,improve the effect of rehabilitation,and reduce the economic burden of family and society.It also can promote patients back to family and society as earlier as possible.

Rehabilitation for Complications and Secondary Disturbance of Traumatic Brain Injury / 中国康复理论与实践

@#The rehabilitation and nursing for the complication and secondary disturbance are the important partition of treatment for patients with traumatic brain injury(TBI).Understanding the category,mechanism,prevention and treatment of complications can efficaciously decrease the incidence rate of them,relieve the distress of patients,increase the ablity of ADL and the quality of life,improve the effect of rehabilitation,and reduce the economic burden of family and society.It also can promote patients back to family and society as earlier as possible.

Mechanism and Issues of Balance Training During Rehabilitation Course of Cerebrovascular Disease (review) / 中国康复理论与实践

@# Balance function is one of injured functions needed rehabilitation after stroke. It is also the considerable signal of the restoration for motor function, which being thought highly in the field of rehabilitation. In some aspect, the restoration of balance function cannot be substituted by stance. The authors mainly discussed the mechanism and issues of balance training by which the balance function of stroke patients in chronic period improved, based on nerve compensative mechanism.

Effects of Constraint-induced Movement Training on Neurological Medullary Sheath in Rats after Middle Cerebral Artery Occlusion / 中国康复理论与实践

@#Objective To study the effects of constraint-induced movement train (CIMT) on the neurological medullary sheath in the rats after middle cerebral artery occlusion (MCAO). Methods 55 SD rats were randomly divided into CIMT group and nature recovery (NR) group after MCAO. The CIMT group were trained with balance beam and rolling cage everyday, with restrictting the movement of the intact upper limbs. The NR group lived in the same condition. The rats in CIMT group were assessed with ethology 5 d, 10 d, 15 d, 30 d and 60 d after operation respectively. At last, 5 rats of each group were checked with MRI, then they were immolated for myelin staining. Results The balance and muscle strength of CIMT group improved better compared with the NR ones (P<0.05), as well as the diameter and the demyelination of neurofibril in the infarcted area. Conclusion CIMT can collect more functional neurofibra and decrease myelinolysis.

Assessment on physical development of Han children in rural area of Huludao city with Heath-Carter somatotype method / 中国组织工程研究

BACKGROUND: There are many methods for investigating the physical development and the somatotype of child. Among them, Heath-Carter so matotype method is a comprehensive evaluation method on somatotype. In this method, 10 items of anthropometric indicators are selected from several dozens of items as assessment indicators for development and somatotype.OBJECTIVE: To analyze the rules and characteristics of soma totype development of Hah children in rural area of Huludao city, so as to supplement the essential data for physical anthropology.DESIGN: Normal children were chosen as the subjects, and cross-sectional investigation was carried out.SETTING: Department of Anatomy, Jinzhou Medical College. PARTICIPANTS: With cluster sampling, the Han children between 7 to 10 years old were selected from central primary school of Mingshuixiang Village of Suizhong County of Huludao city from July 2001 to September 2003. All the selected children should be verified healthy by physical examination at school. The children were divided into two groups according to gender, and each group was divided into 4 subgroups according to age,with 46 to 63 members in each group. There were 8 groups altogether.Complete data of 408 children were collected (male 213, female 195).METHODS: Each indicator was measured twice with Heath-Carter soma to type method and selected the average value. Specialists were responsible for the 10 indicators, and a database was established in computer according to age and gender. Calculated the following indicators in turn: endomorphic factor, mesomorphic factor and ectomorphic factor, coordinate values of X and Y on somatotype chart, Height/Weight1/3, mean of dimensional distances from the average somatotype to all somatotypes in the sample,difference between the two somatotypes in three-dimensional space, percentage of body fat and frequency distribution of each somatotype.MAIN OUTCOME MEASURES: Height, body mass, upper arm circum ference, calf circumference, intracondylar diameters of humerus and femur,skinfold of brachial triceps, subscapular skinfold, skinfold of anterosuperior iliac spine, skinfold of gastrocnemius muscle.RESULTS: All the 408 children entered results analysis. ①Height and body mass of 7 to 10 year old children increased as age went up, indicators of Height/Weight1/3 of 7,8,10 year old girls were higher than boys, that of 9 years old boys was higber than girls, which were related to that the growth of height of 8 & 9 year old boys (5.61 cm) was more than girls (3.88 cm).The content of body fat of girls was more than boys. The 3 somatotype values were 3.2-3.9, 2.3-2.6 and 3.0-3.4 in boys and 3.5-4.6, 1.9-2.6 and 3.3-3.5 in girls, so endomorphic factor and ectomorphic factor were the main factors both in girls and boys, and endomorphic gene in girls was higher than boys, which indicated that the content of body fat of rural children in Hulutao city was relatively high, their bodies were finely high and thin, their skeletal muscle was not so muscular and the hypodermic fat in girls was more abundant. Seen from the comparison of somatotype between boys and girls in each age group, the differences between two somatotypes in the three dimensional space of 7-, 8-, 9-, 10-11 year old groups were 0.46, 0.68, 1.03 and 0.61 respectively, except 7-year old group, there were significant differences in somatotype of boys and girls between each age groups (P ＜ 0.01). ②The average value of somatotype of Han boys in rural area was 3.4-2.5-3.2, which belonged to medial type; that of girls was 4.0-2.3-3.4, which beglonged to ectomorphic endomorphic type. Endomorphic factor and ectomorphic factor were the dominant factors both in boys and girls, whereas mesomorphic factor was relatively low; the frequency of somatotype kept changing as the increase of age. ③Compared with the data at home and abroad, the endomorphic factor of the Han children in rural area in Huludao City was relatively high, while the mesomorphic factor was relatively low, and the ectomorphic factor was almost the same.CONCLUSION: The somatotype of Han children in rural area in Huludao City develops better. Their heights are tall, whereas their skeletal muscles are not so muscular. Somatotype development of children is diversified with age.

Location and expression of apo(a) and apoB in peripheral blood of patients with cardiovascular disease / 北京大学学报(医学版)

Objective:To explore the relationship between the severity of cardiovascular disease with the expression of apolipoprotein(a) [apo(a)] and apolipoprotein B(apoB) in peripheral blood and their location in peripheral blood cells.Methods: In this report,we selected 4 patients with angiography which indicated that three coronary arteries were narrowed and 5 control patients with normal angiography.Arterial blood was collected and analyzed for lipid parameters in plasma.The mRNA expression of apo(a) and apoB in peripheral white blood cells and platelets were determined by RT-PCR and their protein expression by western blot.Moreover,the expression and location of apo(a) and apoB in white blood cells were determined by confocal microscopy and computer 3D analysis.Results: In plasma,levels of high density lipo-protein-cholesterol(HDL-C) and apolipoprotein A-Ⅰ(apoA-Ⅰ) in cardiovascular disease(CVD) patients were significantly less than those in the control patients[(0.62?0.05) mmol/L,(0.78?0.08) mmol/L vs(0.81?0.15) mmol/L,(0.9?0.07) mmol/L,P0.05).Studies with confocal microscopy indicated that proteins of apo(a) and apoB were co-expressed by a few cells of leukocytes and the ratio of apoB/apo(a) in cardiovascular disease patients was significantly less than that in the control patients(optical density value 1.60?0.12 vs 4.40?0.35,P

Study on polymorphism in the apolipoprotein A5 gene in patients with premature coronary heart disease / 北京大学学报(医学版)

Objective:To investigate the association between the apolipoprotein A5(APOA5) -1131T/C polymorphism and premature coronary heart disease in northern Chinese Han population. Methods: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polyacrylamide gel electrophoresis (PAGE), we analyzed the genotype and allele distribution in 140 patients with premature coronary heart disease diagnosed by coronary angiography and 156 healthy controls. The levels of serum lipid profiles were also studied by biochemical methods. Results: The allele frequency of APOA5-1131T/C polymorphism in the premature coronary heart disease group was significantly higher (43.2% vs. 33.0%, P=0.011) than that in the control group. Compared with TT homozygotes, CC homozygotes exhibited a 2.809-fold (95% CI 1.331-5.927) increased risk of developing premature coronary heart disease. Logistic regression analysis found that this correlation was independent of sex, age, body mass index (BMI), smoking history as well as serum total cholesterol(TC), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) levels; In premature coronary heart disease group, the triglyceride(TG) level in CC homozygotes was significantly higher than those in TC heterozygotes or TT homozygotes. Conclusion: The APOA5-1131T/C polymorphism has influence on serum TG level, and the APOA5-1131C allele is associated with the development of premature coronary heart disease in northern Chinese Han population.

Changes of metallothionein contents in plasma and tissues of rabbit with atherosclerosis / 中国病理生理杂志

AIM: To observe the level of metallothionein (MT) in liver, aorta and plasma of rabbit with atherosclerosis (AS) in order to recognize the alteration of oxidative defense system in body when AS occurred.METHODS:Preparation of AS model of rabbit induced by having high-fat diet for eight weeks; the levels of MT and malondialdehyde (MDA) were measured in the tissues of liver and aorta and plasma of rabbit.RESULTS:The MT levels in liver tissues and plasma in atherosclerotic group increased 318%( P

Differential diagnosis value of blink reflex in primary and secondary trigeminal neuralgia / 临床神经病学杂志

0.05). Compared with primary trigeminal neuralgia group and normal control group,the LPs in each wave of BR were significantly prolonged in secondary trigeminal neuralgia group(all P