BACKGROUND: The synaptic plasticity of central nerves is the key basis of behavior-dependent learning and memory, there have been few reports about weather the Chinese herbal medicine for treatment of Alzheimer disease is through enhancing synaptic plasticity to improve learning and memory.OBJECTIVE: To investigate the effect of tiantai No. 1 recipe on learning and memory function and synaptic plasticity of spontaneous Alzheimer disease models.DESIGN: A randomized and controlled trial.SETTING: Institute of Combination of Traditional Chinese Medicine and Western Medicine of Shenzhen.MATERIALS: The experiment was completed at the grade Ⅱ Laboratory of Institute of Combination of Traditional Chinese Medicine and Western Medicine of Shenzhen City. The experimental animals were mice of Kunming strain.METHODS: Totally 52 Kunming mice, aged 21 months, with spontaneous Alzheimer disease (memory impairment) were chosen, and at random divided into 4 groups: senile dementia, western drug control, tiantai No. 1recipe 6.80 g/kg and 20.41 g/kg groups; besides 13 mice with normal learning and memory power were chosen as normal senile group. Hydergine 0.6 mg/kg was given for mice in western drug control group, tiantai No. 1recipe 6.80 g/kg and 20.41 g/kg were respectively given for mice in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups. The medicines above were all prepared into 0.5 mL solution and given by gavage, for consecutive 60 days. The mice in normal senile and senile dementia groups were given double distilled water of the same volume. The learning memory power was tested by jumping stand; ultrathin cerebral section of hippocampal CA1 region was examined with transmission electron microscope,and some parameters of synaptic plasticity was also quantitatively detected with automatic micrographic analysis system.MAIN OUTCOME MEASURES: ① The effect of tiantai No. 1 recipe in different doses on learning and memory of spontaneous Alzheimer disease mice. ② Observation of synapse with electron microscope and quantitative examination stereologically.RESULTS: All animals involved in the trial entered the final result analysis without any loss. ① The effect of tiantai No. 1 recipe in different doses on learning and memory of spontaneous Alzheimer disease mice: The error numbers of learning and memory in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups were smaller than that in senile dementia group,and the error number of learning in tiantai No. 1 recipe 6.80 g/kg group was smaller than that in tiantai No. 1 recipe 20.41 g/kg group. The escape latent periods of learning training was smaller than that in senile dementia group and the safe platform latent periods of memory in tiantai No. 1 recipe 6.80 g/kg and 20.41 g/kg groups were longer than that in senile dementia group, and the safe platform latent period of memory in tiantai No. 1 recipe 6.80 g/kg group was smaller than that in 20.41 g/kg group. ② Observation of synapse with electron microscope and quantitative examination stereologically: Compared with the mice in normal senile group, for mice in senile dementia group, there occurred degenerative phenomena: the number of synapses reduced, a part of synaptic clefts were not clear, the synaptic junction was interrupted, and he sizes of synaptic vesicles were different; in the rest groups there were also degenerative phenomena, however the degrees were milder than those in the model group. Tiantai No. 1 recipe could remarkably raise the number density and sectional density of synapses in the hippocampal CA1 region, and the increased extents in 20.41 g/kg tiantai No.1 recipe was larger than those in 6.80 g/kg tiantai No. 1 recipe.CONCLUSION: Tiantai No. 1 recipe can remarkably improve their learning and memory impairments, which may be related with that it promotes re-generation of synapse and improves the plasticity of cerebral synapses;and the action presented a relationship of dose-effect.

BACKGROUND: The theory of free radical on onset of Alzheimer disease(AD) and the relationship between oxidative damage and onset of AD have made anti-oxidative drugs become the hot topic in researches. Whether does the action of natural Chinese herbs on anti-injury of oxygenic free radical produce intervention on AD?OBJECTIVE: To observe the effects of developed and researched tiantai I,the natural Chinese herb, on learning and memory function and metabolism of oxygenic free radical in the model of spontaneous AD.DESIGN: Completely randomized experimental study based on the experimental animals.SETTING: Clinical Institute of Chinese-Western integration of City-grade.MATERIALS: The experiment was performed in 2nd grade Animal Experimental Room of Clinical Institute of Chinese-Western integration in Shenzhen. Kunming male mice of clean grade were employed, at the age of 13 months, mass weighted varied from 40 to 50 g and from Experimental Animal Center of Zhongshan Medical University(Qualified No. 95A07).INTERVENTIONS: When the experimental animals were bred till 21 months, AD mice were screened from the aged animals according to International Universal Standards and Methods. The experimental animals were randomized into blank control, western-drug control, the small dosage of tiantai I group(small dosage group), the large dosage of tiantai I group(large dosage group) and learning and senile normal-memory group(senile normal group) in addition. In western-drug control, hydergine 0.6 mg/kg was administrated, and in small and large groups, tiantai I of 6. 80 g/kg and 20.41 g/kg were administrated respectively, continuously for 60 days. The double-distilled water of equal dosage was infused in both blank control and senile normal group.MAIN OUTCOME MEASURES: Step-down test was applied to determine learning and memory scores. Froze sections of brain tissue were prepared and immuno-histological-chemical method was used to display the superoxidative dismutase(SOD) activity in cerebral cortex and hippocampus. Ultrathin section of brain tissue in hippocampal CA1 was prepared and transmission electron microscope(TEM) was used to observe cellular lipofuscin in neuron. Automatic image analysis system for biomedical application was used to determine in quantity SOD and lipofuscin.RESULTS: Learning and memory of AD mice were significantly decreased ( P ＜ 0.01 ) . Tiantai I improved significantly learning and memory disturbance of mice in the model of spontaneous AD( P ＜ 0.05- 0.01),markedly enhanced SOD activity in central cerebral cortex and hippocampus ( P ＜ 0.05 - 0.01 ) and reduced cellular lipofuscin content of neuron( P＜ 0.05 -0.01 ). In addition, it provided certain of quantitative reaction.CONCLUSION: For the mice with spontaneous senile dementia, learning and memory as well as SOD activity of neuron in relevant cerebral areas are decreased remarkably and lipofuscin is increased significantly. Tiantai I acts significantly in pharmacodynamics on anti-injury of oxygenic free radical,increases significantly SOD activity, decreases lipofuscin content and improves the ultrastructure of neuron in cortex and hippocampus in AD mice.

Objective To investigate the clinical and genetic characteristics in a patient with 17β-hydroxy-steroid dehydrogenase (17β-HSD) 3 deficiency, regarding its pathophysiology and pathogenesis. Methods Clinical features and laboratory data were analyzed in a pedigree of 17β-HSD3 deficiency. Blood samples from the patient and his parents were collected. HSD17B3 gene was screened for mutations by PCR and subclone sequencing. Results The patient presented with pubertal virilization and gynecomastia. The physical examination showed female external genitalia and testes in inguinal canals. The chromosome karyotype was 46, XY. Serum FSH, LH, dehydroepiandrosterone sulfate, androstenedione and 17-OH-progesterone levels were raised, whereas plasma testosterone was lowered. Sequencing analysis revealed 4 nucleotide deletion (172-175del) of HSD17B3 gene. Conclusion Virilization and gynecomastia in puberty suggest the probability of 17β-HSD deficiency. It may be verified clinically by hCG-stimulating test and confirmed by gene diagnosis.

Objective To observe the effect of berberine on glucose transport in 3T3-L1 adipocytes and to investigate its mechanism. Methods The glucose consumption of the cells was determined by the glucose oxidase method. The glucose transportation rate of the cells was assayed by the uptake of 2-deoxy-〔 3H〕-D-glucose. Protein kinase B (Akt) activity was detected by immunoprecipitation and Western blot. The gene expression of c-Cbl-associated protein (CAP) was detected by Northern blot. Results 0.1～200 ?mol/L berberine significantly increased glucose consumption in 3T3-L1 adipocytes with a dose-dependent effect, which was independent of insulin. The glucose transportation was significantly increased in adipocytes incubated with 0.1～10 ?mol/L berberine; the action began at 2 h and reached a peak value at 12 h. The results of immunoprecipitation and Western blot showed that berberine did not enhance Akt activity. The result of Northern blot indicated that berberine significantly decreased CAP mRNA expression. Conclusion Adipocytes are the important target cells of berberine. Berberine significantly increases glucose transportation and consumption in adipocytes, the action appeares to be independent of insulin signal pathway.

ObjectiveTo investigate the relationships between insulin-like growth factor-Ⅰ (IGF-Ⅰ) and osteoprotegerin (OPG), RANKL, and bone mineral density (BMD) in healthy women. MethodsBMD of lumbar spine and femoral neck were measured in 504 healthy women by dual energy X-ray absorptiometry and their serum levels of IGF-Ⅰ, OPG, RANKL were also determined. ResultsAge was negatively correlated with serum level of IGF-Ⅰ in healthy women (r=-0.702, P

Objective To search the single nucleotide polymorphism (SNP) in exons of osteoprotegerin gene, and to analyse the relationship between SNP and bone mineral densities (BMD) in postmenopausal women. Methods Using PCR and direct sequencing to identify SNP and genotypes in 205 postmenopausal women. BMD at lumbar spine (L 2 4 ) and femoral neck (FN) were measured by dual energy X ray absorptiometry. Serum osteocalcin (BGP), osteoprotegerin (OPG), osteoprotegerin ligand (RANKL) and urinary N telopeptides of type Ⅰ collagen (NTx) were also measured. Results One SNP, G1181C, was found in exon 1 of OPG gene. The frequencies of G1181C genotypes in 205 postmenopausal women were 0.566, 0.346, and 0.088 for the genotypes GG, GC and CC respectively. BMD at lumbar spine (L 2 4 ) of CC genotype was significantly higher than GC and GG genotypes (P

Objective To investigate the effects of control status scale for diabetes (CSSD70), designed by diabetes center of Ruijin Hospital, in type 2 diabetes patients. Methods The correlations between CSSD70 and age, gender, duration of diabetes, educational backgrounds, insulin use, instruments for diabetes control, diabetes family history, symptoms at the onset of diabetes, complications, random plasma glucose and HbA_(1c) were analysed in 136 type 2 diabetes patients. The correlation between CSSD70 and another national questionnaires DQOL was analysed, and in order to determine the validity and stability of CSSD70, 30 patients were asked to complete the scales twice within one week. Results The coherent results in CSSD70 and DQOL were obtained, but CSSD70 was more comprehensive and sensitive. Almost all factors included in this study were related to CSSD70 total score and sub-scale score. The stability of CSSD70 was fine, and a close relationship between total score and sub-scale score was found. Conclusion The CSSD70 appears to be a good scale in evaluating the functional health status in type 2 diabetes, and is suitable for Chinese patients in evaluating diabetes control.

OBJECTIVETo investigate the relationships between the polymorphisms of estrogen receptor (ER) gene, bone mineral density (BMD) and bone biochemical markers in Chinese postmenopausal women.

METHODSBMD of lumbar spine and femoral neck were measured using dual-energy X-ray absorptiometry (DEXA) in 186 Chinese postmenopausal women. The PvuII and XbaI polymorphisms of the ER gene were detected using polymerase chain reaction (PCR). Bone biochemical markers, serum alkaline phosphatase, osteocalcin and pyridinoline were measured by ELISA.

RESULTSThe femoral neck (FN) BMD (Z score) was higher in pp compared to Pp (-0.01 +/- 0.12 vs. -0.35 +/- 0.09, P < 0.05) while lumbar spine BMD (Z score) was higher in XX type compared to Xx and xx genotypes (0.01 +/- 0.45 vs -1.53 +/- 0.17, -1.29 +/- 0.10, < 0.001 and 0.001, respectively). Women without Px haplotype (n = 79) had a higher BMD Z-score for the lumbar spine (-1.03 +/- 0.14 vs -1.45 +/- 0.11, P < 0.05) and femoral neck (-0.01 +/- 0.11 vs -0.31 +/- 0.09, P < 0.05) than those who had it (n = 107).

CONCLUSIONSThe present study suggested that the pp and XX genotypes of ER gene might play a certain role in maintaining FN and lumbar spine BMD. ER genotypes without Px haplotype might be favorable to bone mass, while those with it might exert some harmful effect on bone mineral density.

Aged ; Bone Density ; Female ; Genotype ; Humans ; Middle Aged ; Polymorphism, Genetic ; Postmenopause ; metabolism ; Receptors, Estrogen ; genetics ; Regression Analysis

OBJECTIVETo report the clinical characteristics, biochemical profiles, diagnosis and treatment of one Chinese pedigree with glucocorticoid-remediable aldosteronism (GRA) and to study its molecular mechanism.

METHODSPlasma and urinary aldosterone, cortisol and plasma renin activities were dynamically tested and diagnostic therapy with dexamethasone was undergone in 3 affected subjects. Long-distance PCR as well as DNA sequencing were applied to detect the fusion gene in this pedigree.

RESULTSIn this GRA pedigree, there were 4 affected subjects who had hypertension, hypokalemia and low basic and provoked renin activity. Three patients were given dexamethasone treatment, and had a significant decrease in plasma aldosterone concentrations (PACs) (from 192 +/- 9 ng/L to 87 +/- 7ng/L, P < 0.05) after 5 days. Among them, one patient (II -3) responded quite satisfactorily to the therapy, with serum K(+) rising from baseline value of 2.5 to 2.9, 3.8 and 4.15 mEq/L on the 10th, 28th and 35th days after treatment respectively. Three weeks later, his blood pressure decreased from its original level of 146.3 +/- 1 0.7/94.6 +/- 5.3 mm Hg to 138.3 +/- 3.1/87.3 +/- 6.1 mm Hg (P < 0.05). The other 2 members (III -2 and III -4) showed modest improvement although their PACs decreased significantly. Using long-distance PCR, we found a 3.9 kb band in all 4 affected individuals, which was absent in 5 unaffected members from this pedigree or 8 patients with aldosterone-producing adenoma (APA) or idiopathic hyperaldosteronism (IHA). By DNA sequence analysis, we found that the breakpoint of "unequal crossing-over" is both within intron 2 of the 11beta-hydroxylase gene (CYP11B1) and the aldosterone synthase gene (CYP11B2).

CONCLUSIONSThe excess of mineralocorticoid in patients with GRA can be inhibited by exogenous glucocorticoids. The fusion gene resulting from unequal crossing-over between the 11beta-hydroxylase gene and the aldosterone synthase gene is the pathogenesis of this Chinese GRA pedigree.

Adrenocorticotropic Hormone ; physiology ; Adult ; Aldosterone ; blood ; Female ; Glucocorticoids ; therapeutic use ; Humans ; Hyperaldosteronism ; blood ; drug therapy ; genetics ; Mutation ; Pedigree