In the study, the inhibitory effect of epigallocatechin gallate (EGCG) on Calcium oxalate nephrolithiasis and its possible mechanism were investigated. The rat Calcium oxalate nephrolithiasis model was induced through the combined oral administration of ethylene glycol and ammonium chloride, which was intervened with EGCG. Rat blood samples were collected to detect blood creatinine (Cr), blood urea nitrogen (BUN) and blood calcium. Rat urine samples were collected to observe and compare 24-hour urine volume, oxalic acid (Ox) and calcium in urine. Renal samples were collected to prepare tissue slices and observe the pathological changes in Calcium oxalate nephrolithiasis. The expression of osteopontin (OPN) in renal tissues was evaluated by Real-time PCR and Western blot. According to the results, compared with normal rats, rats in the nephrolithiasis model showed significant increases in Cr, BUN, urine Calcium, urine Ox and renal OPN expression (P < 0.05), but obvious decrease in 24-hour urine volume (P < 0.05); Compared with rats with nephrolithiasis, those processed with EGCG revealed remarkable declines in Cr, BUN, urine Calcium and urine Ox (P < 0.05), with significant rise in 24-hour urine volume (P < 0.05) in a concentration-dependent manner. Additionally, compared with the control group, nephrolithiasis rats showed significant pathological changes in Calcium oxalate calculus. After ECCG treatment, the renal pathological changes and OPN expression attenuated significantly in a concentration-dependent manner. The results showed that EGCG inhibits the formation of calcium oxalate nephrolithiasis in rats and shows a notable protective effect on renal functions.
Animals ; Blood Urea Nitrogen ; Calcium ; blood ; Calcium Oxalate ; metabolism ; Catechin ; administration & dosage ; analogs & derivatives ; Creatinine ; blood ; Disease Models, Animal ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Nephrolithiasis ; blood ; drug therapy ; genetics ; Osteopontin ; genetics ; metabolism ; Rats ; Rats, Wistar

Child ; Humans ; Proteomics ; methods

Cell Line, Tumor ; Enzyme Inhibitors ; pharmacology ; Heterocyclic Compounds, 1-Ring ; pharmacology ; Humans ; Proteasome Endopeptidase Complex ; drug effects

Aim Toinvestigatetheroleofbrain-de-rived neurotrophic factor(BDNF)-tyrosine receptor ki-nase B (trkB ) signaling pathway in the therapeutic effects of ketamine on diabetic neuropathic pain.Meth-ods Forty-eightWistarrats,aged3months,weighing 200~250 g,were equally randomized into 4 groups(n=12 ):control group (C group ), saline group (S group),ketamine group (K group)and ketamine +ANA-12 group (KA group ).Rats in S,K and KA groups were intraperitoneally injected with a single of streptozotocin(STZ)65 mg·kg-1 to construct diabetic neuropathic pain model.After twenty-eight days,rats in S,K and KA groups were intraperitoneally injected with saline, ketamine 10 mg·kg-1 and ketamine 10 mg·kg-1 +ANA-12 0. 5 mg·kg-1 for consecutive 7 days, respectively. On the 8th day, mechanical withdrawal threshold(MWT)of rats was measured.Af-ter that,the rats were immediately sacrificed,and dor-sal ganglion of lumbar spine and prefrontal cortex (PFC)were harvested for measuring BDNF,p-trkB/trkB,synaptophysin and spine density by Western blot andglogistaining.Results ComparedwithCgroup, rats in S group significantly decreased MWT,BDNF, p-trkB/trkB,synaptophysin and spine density in dorsal ganglion and PFC (P <0. 05 ).Compared with S group,rats in K group showed a significant increase of MWT,BDNF,p-trkB/trkB,synaptophysin and spine density in the all observed regions(P<0. 05 ).On the contrary,rats in KA group showed a significant de-crease of MWT and BDNF,p-trkB/trkB,synaptophys-in and spine density as compared with K group in all regions(P<0. 05 ).Furthermore,BDNF was positive-ly correlated with spine density in all regions (P <0.05).Conclusion BDNF-trkBsignalingpathway mediates ketamine-induced therapeutic effects in dia-betic neuropathic pain.

OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.

RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.

CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.

Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits

OBJECTIVETo study the constituents with the pain-relieving activity from the stem rind of Daphne giraldii.

METHODThe partition of the ethanol extract and chromatographic separation of the fractions were carried out by the monitoring of anelgesic pharmacological activity. The structures of the isolated compounds were determined by MS and NMR.

RESULTFour compounds were isolated from the pain-relieving fraction. Three of them were identified as diterpenes, gniditrin (1), gnidicin (2) and daphnetoxin (3). Compound 4 was determined as Z-octadecyl caffeate.

CONCLUSIONCompounds 1, 2 and 4 were isolated from the plant for the first time.

Analgesics ; chemistry ; isolation & purification ; pharmacology ; Caffeic Acids ; chemistry ; isolation & purification ; pharmacology ; Daphne ; chemistry ; Diterpenes ; chemistry ; isolation & purification ; pharmacology ; Heterocyclic Compounds, 4 or More Rings ; chemistry ; isolation & purification ; pharmacology ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry

Objective To investigate the effect and underlying mechanism of apolipoprotein E (APOE) genetic polymorphism in treating blood brain barrier (BBB) breakdown after traumatic brain injury (TBI).Methods Human APOE knock-in mice (ε3,ε4),APOE knockout mice,and APOE wild-type mice with each numbering 80 were respectively divided into TBI group (n =50),sham-operation group (n =15) and normal control group (n =15) according to the random number table.TBI group was subdivided at 1 day (n=15),3 days (n=15),and7 days (n=20).TBI was induced with a pneumatically operated injury device.BBB permeability to large or small molecules was evaluated by measuring Evans blue (EB) and fluorescein sodium (NaFI) extravasation into the damage area at 1,3,and 7 days postinjury.Brain water content was determined using the dry-wet method.Western blotting and qRT-PCR for tight junction-associated proteins Occludin and Claudin-5 were performed at 7 days postinjury.Results With respect to normal control group,BBB permeability to EB and NaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice.There appeared significant increase in BBB permeability to EB and NaFI in TBI group,with insignificant differences among rats of each genotype at 1 and 3 days postinjury (P ＞ 0.05).Whereas at 7 days postinjury,BBB permeability to EB in APOE wild-type and e3 mice returned to the normal level (P ＞ 0.05),but it re mained at a high level in APOE knockout and ε4 mice (P ＜ 0.01).Meanwhile,BBB permeability toNaFI was significantly higher in ε4 and APOE knockout mice than in ε3 and APOE wild-type mice (P ＜ 0.01).Brain water content was equivalent among rats of each genotype at 1,3 and 7 days postinjury (P ＞0.05).Western blotting and qRT-PCR demonstrated Occludin and Claudin-5 in ε4 and APOE knockout mice were significantly lower than those in ε3 and APOE wide-type mice (P ＜ 0.05).Conclusion APOE plays an important role in restoration of BBB function after TBI,but ε4 may impede the recovery of BBB breakdown after TBI through its effect on tight junction.

Objective To investigate the changes of sympathovagal balance and the effects of va- gus stimulation on sympathovagal balance in endotoxemia rats.Methods Twenty-four Spragne Dawley rats were randomly divided into four groups.The frequency domain of heart rate variability(HRV)com- ponent was analyzed at 0 min,2 ,4 and 6 hours after intravenous injection of lipopolysaccharide(LPS, 5mg/kg)or physiologic saline,and cervical vagal nerve was stimulated(5mv,2ms,1Hz,5 min lasted, 20 min interval)when LPS or physiologic saline was injected.The levels of Noepinephine(NE)and Ace- tylcholin(ACh)were measured in liver tissues.Results Normalized low frequency(LFnm),hormali- zed high frequency(HFnm),very low frequency(VLF),LF/HF values and liver ACh were significantly increased(P＜0.05)and the level of liver NE was significantly decreased (P＜0.05)after LPS admin- istration.Vagal nerve stimulation markedly increased HFnm but decreased LFnm,VLF,LF/HF values, and the liver ACh also significant increased(P＜0.05 ).Conclusion The results suggest that the ac- tivity of sympathetic and vagal nerve was increased during endotoxemia,but the sympathetic activity was more excitable than that of vagal nerve.Vagal nerve stimulation increased the tone of vagus nerve while the tone of sympathetic nerve was decreased in this study.This may be beneficial for anti-inflammatory activity of vagal nerve.

Objective To discuss the midterm results of modular femoral prosthesis in total hip revision surgery for bone defects.Methods From December 2001 to June 2006,by using Link-MP modular femoral prosthesis for muhiple reasons(48 with asepsis loosening,seven with infections using two-stage revision procedure,one with fracture of proximal femur and one with periprosthetie fracture), total hip revision surgery was carried out in 56 eases including 24 males and 32 females with age range of 38-77 years(mean age 58.8years).Causes for revision included sterile prothesis loosening in 48 cases, infection of hip prosthesis in seven and peripheral fracture of femoral stem fracture prosthesis in one.Re- vision for infected femur was all at stageⅡ.Of 56 cases with femoral stem prosthesis loosening,30 had loosening of primary cemented prosthesis and 26 of uncemented prosthesis.According to the Mallory bone defect classification,five eases were with typeⅡbone defect,21 with typeⅢA,28 with typeⅢB and two with typeⅢC.Bone grafting was performed in 12 cases and wire or cable cerelage in 28.Fracture of great trochanter was found in two cases,fracture of femoral stem in three and perforation of femoral stem in one.Results A total of 52 eases half year after operation were followed up for mean 31.78 months (8-56 months).No migration of distal femoral stem was found in all eases except for one ease had 1.5 cm subsidence of proximal femoral stem.The Harris hip score was preoperative 46 scores(21-52)and post- operative 89(79-94).There found no significant limb discrepancy,thigh pain or dislocation.Conclu- sions Total hip revision surgery for femoral bone defect using modular femoral prosthesis has optimal midterm result especially in its advantages of regulating limb length,offset,anteversion,which can help us match the proximal femur with distal femur and achieve initial and long-term stability.

BACKGROUND: Sinomenine is an alkaloid monomer extracted from a Chinese medicinal herb sinomenium acutum stem. It is used in the therapy of the rheumatoid arthritis and has clear and definite therapeutic effects, but the therapeutic mechanism is unclear.OBJECTIVE: To observe the effect of sinomenine at different doses in vitro on the activity of nuclear factor-κB(NF-κβ) and mRNA expressions of the tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β) andinterleukin-10 (IL-10) in the synovial cells of the rats with adjuvant arthritis(AA) to explore the probable mechanism of sinomenine in the treatment of rheumatoid arthritis(RA).DESIGN: A controlled repeated measuring study based on the cells.SETTING: Department of traditional chinese medicine and the institute of burn research of a military medical university.MATERIALS: This study was finished at the Laboratory of the Institute of Burn Research of Chinese PLA. The experimental animals were 25 healthy male Wistar rats of clean grade. The AA model rats were made and the synovial cells were collected and grouped as follows: normal control group, AA group,AA + sinomenine 30 mg/L group, AA + sinomenine 60 mg/L group, AA + sinomenine 120 mg/L group. The activity of the NF-κB was measured by the electrophoresis mobility shift assay(EMSA) . The mRNA expressions of the TNF-α, IL-1β and IL-10 were measured by reverse transcription-PCR assay.MAIN OUTCOME MEASURES: The results of the changes of the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells of the rats with adjuvant arthritis after the treatment with sinomenine at different doses.RESULTS: Compared with the normal control group, the activity of the NF-κB and the mRNA expressions of the TNF-α, IL-1β and IL-10 in the synovial cells in the AA group all increased significantly and the outcomes were 17±6, 0.570±0.047, 0.730±0.093, 0. 683 ±0.081 (t= 2.71 -4.07, P < 0.05). After the administration of sinomenine, the activity of NF-κB showed a good correlation with mRNA expressions of the TNF-αandIL-13(r=0.810, P <0.001; r=0.562, P <0.05), but no statistical relevance with mRNA expression of IL-10 was established. Sinomenine showed a dose-dependent inhibition on the activity of the NF-κB and the mRNA expressions of the TNF-α and IL-1β in a certain range of concentrations(30-120 mg/L), but no dose-dependent inhibition on mRNA expression of the IL-10 was observed.CONCLUSION: Through the inhibition of the activity of the NF-κB,sinomenine decreased the mRNA expressions of the TNF-α and the IL-1β in the synovial membrane cells.