? amyloid protein(A?) including A?40 and A?42 are the important bioactive substances in vivo.Their toxic and beneficial attributes in the body depend on its concentration.The brain A? level is maintained by two balances under the physiological condition.The first balance is the generation involved in ?-secretase and ?-secretase and the degradation involved in neprilysin(NEP) and insulin-degrading enzyme(IDE) of A?. The second one is the balance between the receptor for advanced end glycation products(RAGE)-mediated influx and low-density lipoprotein receptor related protein 1(LRP1)-mediated efflux of A? across the blood-brain barrier(BBB).Breakdowning any one of the two balances would result in the aggregation and precipitation of A? in the brain,which is a crucial event in the pathogenesis of Alzheimer's disease(AD).This paper reviews the regulation of brain A? level under the physiological condition and the reducing strategies on the level of brain A? under the pathological condition for developing new drugs in the treatment of AD.

Objective To observe the acute skin and mucous membrane reactions in patients treated with concurrent radiochemotherapy for nasopharyngeal carcinoma,and to analyze the influencing factors.Methods A total of 85 nasopharyngeal carcinoma cases treated with concurrent radiochemotherapy were enrolled in the study.Fifteen clinical and laboratory indexes,including BMI,radiation dose,degree of acute oral mucous and skin reactions and blood routine test were observed weekly.Univariate and multivariate regression analysis were performed to assess the factors,and screen the independent factors.Results Multiple-factor analysis showed that the risk factors cloesly related with acute radioactive oral mucosa reactions were smoking history(OR =3.467,P ＜ 0.05),single-dose of gross tumor volume (GTV) ＞2.15 Gy(OR =3.393,P ＜ 0.05),while those with acute radiation skin reactions were diabetes history(OR =87.859,P ＜ 0.05) and hemoglobin values 1 week before radiotherapy ＞ 130 g/L (OR =21.404,P ＜ 0.05).Conclusions In the patients treated with concurrent radiochemotherapy for nasopharyngeal carcinoma,smoking history and single-dose of GTVnx is the independent risk factors of acute radiation oral mucosa reactions,while diabetes history and hemoglobin values I week before radiotherapy are the independent factors of acute skin reactions.

OBJECTIVETo observe the clinical effect of Chinese medical (CM) syndrome differentiation based Chinese herbs and recombinant human tumor necrosis factor receptor II-antibody fusion protein (etanercept) for treating ankylosing spondylitis (AS) patients.

METHODSTotally 35 AS patients were treated with syndrome differentiation based Chinese herbs and etanercept. Reinforcing Shen and strengthening Du channel, activating meridians to stop pain was principle used in syndrome differentiation based treatment. Etanercept was subcutaneously injected, 25 mg each time; twice per week for the first three months and once a week for the latter three months. The clinical efficacy was evaluated after 3 and 6 months of treatment. Meanwhile, ASAS20 and ASAS50 standards arriving rates were also observed. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), visual analog score (VAS) for spine pain, VAS for night pain, patient global assessment (PGA), VAS for physician global assessment, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, cervical rotation, Schober improved test, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were observed before treatment, 3 and 6 months after treatment.

RESULTSCompared with before treatment, BASDAI, BASFI, VAS for spine pain, night pain, physician global assessment, PGA, CM syndrome score, finger-ground distance, thoracic activity, tragus-wall distance, lumbar scoliosis, Schober improved test, ESR, and CRP all decreased after 3 and 6 months of treatment, with statistical difference (P < 0.05). Cervical rotation also decreased after 6 months of treatment, with statistical difference (P < 0.05). Compared with 3 months of treatment, total effective rate of CM syndrome, ASAS20 and ASAS50 standards arriving rates increased after 6 months of treatment, with statistical difference (P < 0.05). There were statistical differences in all indices mentioned above between after 3 months of treatment and after 6 months of treatment (P < 0.05).

CONCLUSIONSyndrome differentiation based Chinese herbs combined etanercept could alleviate inflammatory reaction favorably, control the progression of active AS, and improve joint functions.

Disease Progression ; Drugs, Chinese Herbal ; therapeutic use ; Etanercept ; therapeutic use ; Humans ; Pain ; prevention & control ; Pain Management ; Spondylitis, Ankylosing ; drug therapy ; Treatment Outcome

Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Silicosis ; diagnostic imaging ; Tomography, Spiral Computed

Objective To investigate the clinical effect of estrogen combined with progestogen replacement therapy on patients with secondary premature ovary failure (POF) induced by Triptergium wifordii (TW). Methods Twenty-one patients who suffered from secondary suspend menses by TW were treated by estrogen combined with progestogen replacement therapy periodically. The serum levels of E2, LH and FSH were examined and changes of menses and clinical manifestations were observed respectively before and 3 months after the ending of treatment.Results All of the patients were confirmed as POF according to the levels of blood sexual hormone and clinical manifestations. The E2 secreted by ovary was higher [ (392.90?77.53 )pmol/L vs. (83.47?8.46)pmol/L, P

Objective To assess the tolerance of elderly patients with esophageal carcinoma to chemoradiotherapy through.Methods A retrospective analysis of 596 elderly patients with esophageal carcinoma receiving chemoradiotherapy was conducted.Patients were divided into radiachemotherapy group and radiotherapy group,and according to age,patients were divided into four age groups (aged 70-74,75-79,80 80 and 85years and over).The tolerance to treatment was assessed by Charlson index.Results 185 patients completed chemoradiotherapy,113 patients reduced the dose of chemotherapy (reduction group),81 patients unfinished chemoradiotherapy (unfinished CRT group),160 patients completed radical radiotherapy alone (unfinished RT group),and 57 patients incompleted radiotherapy.Further analysis found that the tolerance to treatment in reduction group had significant differences between patients aged ≥ 75 years and ＜ 75 years (x2 =6.815,P=0.009),and between WIC ≥ 1 and ＜ 1(x2 =10.636,P=0.001); the tolerance to treatment in unfinished CRT group had significantly differences between aged ≥ 80 years and ＜80 years (x2 =63.842,P=0.000),and between WIC =0,1 and ≥ 2 (x2 =21.153,P=0.000).Conclusions Further age re-grouping and WIC assessment is necessary before treating esophageal cancer patients.Reduction of therapy dosage is more beneficial for patients aged ≥ 75 years and WIC≥1,and greater caution is required in chemotherapy for patients aged ≥ 80 years and WIC＞1.

AIM: To study the effect of breviscapine on the oxidative stress in the liver and kidney in diabetic rats. METHODS: Diabetes was induced by injection of streptozotocin (ST Z). Rats were randomly divided into three groups: control group, model group, mo del group treated with breviscapine. 8 weeks after STZ injection, liver lesion w as evaluated using HE, oil red O staining and kideny lesion using PAS staining. Malondiadehyde (MDA) levels and antioxidant activities in liver and kidney tissu e were determined by spectrophotometric method. RESULTS: Light microscopy in HE staining showed that liver fatty score was significantly lower in the breviscapine group compared with model ani mals (0.55?0.43 vs 1.54?0.65, P

OBJECTIVETo discuss the protective effect of alkaloids from Piper longum (PLA) in rat dopaminergic neuron injury of 6-OHDA-induced Parkinson's disease and its possible mechanism.

METHODThe rat PD model was established by injecting 6-OHDA into the unilateral striatum with a brain solid positioner. The PD rats were divided into the PLA group (50 mg x kg(-1) x d(-1)), the madorpa group (50 mg x kg(-1) x d(-1)) and the model group, with 15 rats in each group. All of the rats were orally given drugs once a day for 6 weeks. Meanwhile, other 15 rats were randomly selected as the sham operation group, and only injected with normal saline in the unilateral striatum. The behavioral changes were observed with the apomorphine (APO)-induced rotation and rotary rod tests. The number of tyrosine hydroxylase (TH)-positive cells in rat substantia nigra and the density of TH-positive fibers in striatum were detected by tyrosine hydroxylase immunohistochemistry. The content of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione (GSH), catalase (CAT), malondialdehyde (MDA), nitric oxide (NO) and nitric oxide synthase (NOS) in rat substantia nigra and striatum were measured by the spectrophotometric method.

RESULTAfter being induced by APO, PD rats showed obvious rotation behaviors, with decreased time stay on rotary rod and significant reduction in the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. The activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity significantly decreased, whereas the activities of NOS and the content of MDA, NO significantly increased. PLA could significantly improve the behavioral abnormality of PD rats and increase the number of TH-positive cells in sustantia nigra and the density of TH-positive fibers in striatum. It could up-regulate the activities of SOD, GSH-Px, CAT, the content of GSH and the total antioxidant capacity, and decrease the content of NOS and the content of MDA, NO.

CONCLUSIONAlkaloids from P. longum shows the protective effect in substantia nigra cells of 6-OHDA-induced PD model rats. Its mechanism may be related with their antioxidant activity.

Administration, Oral ; Alkaloids ; administration & dosage ; pharmacology ; Animals ; Apomorphine ; pharmacology ; Catalase ; metabolism ; Dopamine Agonists ; pharmacology ; Dopaminergic Neurons ; drug effects ; metabolism ; pathology ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Motor Activity ; drug effects ; Neostriatum ; drug effects ; metabolism ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Oxidopamine ; Parkinson Disease, Secondary ; chemically induced ; physiopathology ; prevention & control ; Piper ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Substantia Nigra ; drug effects ; metabolism ; Superoxide Dismutase ; metabolism ; Tyrosine 3-Monooxygenase ; metabolism

AIMTo search for flavonoids which possess stronger vasorelaxation action.

METHODSFour quercetin glycosides (1a - d) were synthesized from quercetin in three steps i. e. selective protection of quercetin, condensation with corresponding acetyiglycosyl bromide, and then removal of the protecting group; Six flavone compounds (2a - f) were prepared from phloroglucinol according to the conventional methods; The structures of synthetic compounds were confirmed by IR, 1H NMR, 13C NMR and MS. Vasorelaxation action of ten synthetic quercetin derivatives (or analogues) and four natural flavonoids compounds were examined on the isolated rat thoracic aorta rings; Comparative octanol-water partition coefficients (logP) were measured using a reversed-phase HPLC method.

RESULTSMost of the tested flavonoids showed concentration dependent relaxation effects against PE-induced contractions of rat aortic rings. These compounds had stronger action with the augment of logP values.

CONCLUSIONCompound 3-bromo-5 ,7-dihydroxyflavone (2d) was identified to have the most potent vasodilating action. These compounds exert vasodilating effects that are related to the logP values. A structure-activity relationship of flavonoids was suggested.

Animals ; Aorta, Thoracic ; drug effects ; Dose-Response Relationship, Drug ; Flavonoids ; chemical synthesis ; chemistry ; pharmacology ; Male ; Molecular Conformation ; Molecular Structure ; Quercetin ; administration & dosage ; analogs & derivatives ; chemical synthesis ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Structure-Activity Relationship ; Vasodilation ; drug effects ; Vasodilator Agents ; administration & dosage ; chemical synthesis ; pharmacology

OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P<0.01 ),sugar tolerance in F2 male group was i mpaired (P<0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P <0.05);seru m insulin were decreased (P<0.05)and male rats showed i mpaired glucose tolerance (P<0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P <0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P <0.05,P <0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.