Melatonin (N-acetyl-5-methoxytryptamine, MT) is a hormone synthesized and secreted by the pineal gland. Recent studies show that melatonin plays an essential role in the pathogenesis of many reproductive processes. High-concentration melatonin exists in human preovulatory follicular fluid and melatonin receptors are present in ovarian granulosa cells, which indicates the direct effects of melatonin on ovarian function. Reactive oxygen species are involved in a number of reproductive events, including folliculogenesis, follicular atresia, ovulation, oocyte maturation, and corpus luteum formation. Melatonin and its metabolites, as powerful antioxidants and free radical scavengers, can potentially inhibit premature ovarian failure. Literature published in recent years shows the essential roles of melatonin in improving human ovarian function and oocyte quality as well as in the management of infertility. Researches on the action mechanisms of melatonin may provide a theoretical basis for the prevention and treatment of some clinical diseases.
Female ; Granulosa Cells ; metabolism ; physiology ; Humans ; Melatonin ; metabolism ; physiology ; Ovarian Follicle ; growth & development ; metabolism ; Ovary ; physiology ; Reactive Oxygen Species ; metabolism

Objective To study the effect of the PDE5 inhibitor on noise-induced hearing loss .Methods 30 guinea pigs were randomly divided into control group ,noise exposure group and PDE5 inbibiter group(10 in each) . Two weeks after white noise exposure of 110 dB ,sildenafil (10 mg?kg -1 ?d-1 ) and NS(4 ml?kg -1 ?d-1 ) were injected into guinea pigs of PDE5 inbibiter group and the noise group respectively .One week after noise exposure four weeks continuous administration was cavried out .The ABR thresholds and the PL of wave Ⅰ were measured respectively prior to the experiment ,1 week post-noise ,1 ,2 and 4 weeks post-drugs .The changes of cochlea hair cells were also observed by light microscopy .Results The ABR threshold shifts and the PL in sildenafil group were less obvious than that of in the noise group .The number of OHCs loss was relatively stable in the normal group , while the obvious OHC loss was observed in other groups .There was significant difference among the three groups , however ,the OHC loss in the sildenafil treatment group was not significantly different from that in the noise expo‐sure (P>0 .05) .Conclusion The inhibitor of PDE5 is able to reduce the decrease of ABR thresholds shift ,shorten the extension of the PL ,and it can significantly protect against noise-induced hearing loss .

OBJECTIVE: To study the effects of sildenafil on morphology to noise-induced hearing loss in guinea pigs. METHOD: Guinea pigs were randomly divided into control group, noise exposure group and the sildenafil treatment group, 12 in each group. a week after white noise exposure of 110 dB, sildenafil (10 mg/kg x d) and NS (4 ml/kg x d) were injected into guinea pigs of the sildenafil treatment group and noise exposure group respectively for four continuous weeks. ABR thresholds were measured respectively prior to the experiment, 1 week post-noise, 1, 2 and 4 weeks post-drugs, the changes of cochlea hair cells were also observed with a scan electron microscope (SEM) and light microscope. RESULT: The ABR threshold shifts in the sildenafil treatment group were significantly fewer than that in the noise exposure group. SEM showed that hear hair of the inner and outer hair cells in noise exposure group displayed mess, fusion and imperfections. In the sildenafil treatment group, the hair cells displayed slight pathological changes, there wasn't significant differents comparied with normal group. The number of OHCs were relatively stable in the normal group, while the obvious OHC loss was observed in other groups. There was significant difference among the three groups, however, the OHC loss in the sildenafil treatment group was not significantly different to that in the noise exposure (P > 0.05). CONCLUSION Sildenafil can significantly protect against noise-induced hearing loss.
Animals ; Guinea Pigs ; Hair Cells, Auditory, Outer ; drug effects ; pathology ; Hearing Loss, Noise-Induced ; drug therapy ; Noise ; Sildenafil Citrate ; therapeutic use

Objective To study the concentration of plasma total homocysteine(tHcy) in patients with chronic renal failure(CRF).Methods 105 chronic renal failure patients and 35 health individuals to our hospital were chosen to measure the level of tHcy using enzymatic cycling assay method.Results The mean level of tHcy in renal failure period C RF patients was significantly higher than that in normal controls (t =3.12,P ＜ 0.05),and the level of plasma tHcy was significantly higher in Uremia stage than in renal failure period in CRF patients (t =6.41,P ＜0.05),and the level of plasma tHcy was significantly higher in renal failure period than in renal function decompensated period in CRF patients (t =11.27,P ＜ 0.05).Conclusion The level of plasma tHcy were significantly elevated in patients with CRF,and there is a trend that the level of plasma tHcy increases with severity of CRF.Serum tHcy concentration have significant value in the diagnosis and understanding the condition of patients with CRF.

BACKGROUND:Demineralized bone can be used as the scaffolds of osteoblasts,and body tissue developed immunologic rejection to demineralized bone.OBJECTIVE:To investigate the histological changes of cyclosporin A(CSA) effect on ossification of demineralized bone,in addition,to explore the feasibility of demineralized bone served as ideal available bone substitute material.DESIGN,TIME AND SETTING:The randomized control experiment of animals was performed at the Experimental Center of Second Hospital of Dalian Medical University between March 2007 and April 2008.MATERIALS:Sixteen New Zealand rabbits were divided into the control and experimental group of homogenic decalcified bone,control and experimental group of heterogenous decalcified bone.CSA was produced by Beijing Novartis Pharmaceutical Co.,Ltd.METHODS:Decalcified bone prepared from rabbits was served as homogenic decalcified bone,and decalcified bone prepared from dogs were served as heterogenous decalcified bone.Sixteen rabbits were randomly divided into 4 groups:the control and experimental group of homogenic decalcified bone,control and experimental group of heterogenous decalcified bone,with 4 rabbits in each group.Each rabbit was implanted with homogenic or heterogenous decalcified bone,respectively,2 samples per side.2 mg/kg CSA or 2 mg/kg placebo was intramuscular injected in the experimental or control groups for 4 weeks.Samples were examined by hematoxylin-eosin staining and light microscope.MAIN OUTCOME MEASURES:The histological observation of decalcified bone in each group.RESULTS:Homogenic allogeneic bone induced formation in all implants.CSA did not induce morphological changes of homogenic allogeneic bone.In the heterogenous decalcified bone treated group,at 4 weeks,there was no bone formation or chondrocytes production in the control group,but there was cartilage and bone formation in the experimental group.CONCLUSION:CSA did not alter the morphology of bone induction by homogenic allogeneic bone.Immunologic reactions may inhibit bone induction by heterogenous decalcified bone,which can be counteracted by treatment with CSA.CSA can increase the rate of nonunion or bone defect using heterogenous decalcified bone.

Objective To investigate the effects of methylprednisolone (MP) on the recovery of postoperative neurological functions due to cervical spondylotic myelopathy.Methods 114 patients with cervical spondylotic myelopathy were divided into the MP group and the control group with 57 cases in each group. The cases of the MP group were treated with MP (20 mg/kg, iv) 30 min prior to the decompression. Those of the control group underwent anterior decompression only. The complications of patients in two groups were compared. The neurological functions of all patients were graded according the ASIA score system preoperatively and at 1st day, 2nd week and 6th month postoperatively.Results Compared with the control group, the neurological functions of the cases in the MP group improved significantly after operation ( P＜0.05).Conclusion For patients with cervical spondylotic myelopathy, MP used during operation can improve postoperative neurological function recovery.

Objective: To study the impact of vascular injury on neointimal hyperplasia and the expressions of nuclear transcription factor-κb (NF-κb), tissue factor (TF), endothelin-1 (ET-1) and matrix metalloproteinase-3 (MMP-3) in experimental rabbit model.
Methods:A total of 32 male New Zealand big-eared white rabbits were used to establish vascular injury model by femoral artery puncture, balloon was sent to abdominal aorta via the wire followed by balloon dilatation to strain abdominal aorta. Blood sample was taken from femoral artery sheath 1 minute after operation, and the rabbits were killed at 4 weeks after operation, meanwhile blood sample was taken from the heart. Injured arteries were isolated, ifxed and embedded; slices were stained by HE, basic fuchsine and NF-κb immunohistochemical methods for light microscope observation; slices were also stained by lead and uranium for transmission electron microscope observation. Neointimal thickness was measured by computer analysis, vascular injury integral and NF-κb positive cell rate were determined, blood levels of TF, ET-1 and MMP-3 were examined by ELISA. The relationship between vascular injury integral and the contents of TF, ET-1, MMP-3 and NF-κb positive cell rate were analyzed by SPSS statistical software.
Results: The optimal iftting curve between vascular injury integral and neointimal thickness was S-shaped cubic curve. NF-κb was mainly expressed in neointima, vascular injury integral was positively related to NF-κb positive cell percentage, Pearson correlation coeffcient was 0.916,P<0.05. Vascular injury integral was positively related to the contents of 1 min post-operative TF; 1 min and 4 weeks post-operative ET-1; 1 min and 4 weeks post-operative MMP-3; Pearson correlation coeffcients were 0.925, 0.957, 0.947, 0.914 and 0.940 respectively, allP<0.05.
Conclusion: Vascular injury may activate NF-κb pathway, promote ET-1 and MMP-3 expression, therefore accelerating neointimal hyperplasia, leading negative vascular remodeling, TF was an initiating factor for neointimal hyperplasia. Internal elastic lamina was the key structure reflecting vascular injury, it is the only barrier hindering neointimal hyperplasia in experimental rabbit model.

The addition of nature substances such as soybean oil, carrot extract, tomato extract, wastes of tobacco industry and citrus molasses to growth medium was shown to strengthen the formation of Coenzyme Q 10 Some of these substances act as precursors of Coenzyme Q 10 and Beta Carotene, and others such as wastes of tobacco industry and Beta Carotene act as inhibitors of Beta Carotene; they all can strengthen the formation of Coenzyme Q 10 Immediately relationship between the biosynthesis of Coenzyme Q 10 and Beta Carotene has been detected

Objective To evaluate the analytical performance of Mindray BS‐820 automatic biochemical analysis system used in primary hospitals in Guangzhou area for verifying whether its performance meeting the clinical requirements .Methods Accord‐ing to the EP5‐A2 ,EP6‐A ,EP7‐A2 and EP‐17A files recommended by CLSI and the Pharmaceutical Industry Standard of the Peo‐ple′s Republic of China YY/T0654‐2008 ,the precision ,linear rang ,anti‐interference capability ,sensitivity and carry‐over rate of the Mindray BS‐820 automatic biochemical analysis system were evaluated by adopting 16 routine biochemical items .Results The pre‐cision results of all 16 analyzing items conducted by the Mindray BS‐820 automatic chemical analysis system conformed to the re‐quirements .The results of 15 items showed good linear relation during the testing range (r≥0 .997 9) .In 16 biochemical items ,the anti‐interference capability of TBIL ,TP ,TC ,TG ,LDL ,HDL ,UREA and Ca to bilirubin ,triglyceride and hemoglobin conformed to or were higher than the anti‐interference capability declared by manufacturer ,but among other 8 items ,the anti‐interference capabil‐ity of 3 items was lower than that declared by manufacturer .The limit of blank(LOB) of all 16 analyzing items was less than LOB in the kit instruction .The carry‐over rate of Glu was 0 .02% ,less than 0 .50% .Conclusion This instrument has good precision , sensitivity and low carry‐over rate(0 .02% ) ,the linear range is ideal ,r≥0 .997 9 ,the anti‐interference capability basically satisfies the clinical needs .Therefore this instrument is suitable for the use in the middle‐small scale laboratory department .

OBJECTIVEEndothelial apoptosis plays an important role in the initiation of atherosclerosis. It would be useful to clarify whether activation of non-neuronal muscarinic receptor (NNMR) could prevent endothelial apoptosis and atherosclerosis. We investigated the effects of NNMR activation on regulating rat aortic endothelial cells (RAECs) apoptosis induced by homocysteine, an independent risk factor of atherosclerosis, and further studied its molecular mechanism.

METHODSRAECs were incubated using homocysteine at the concentration of 2.7 mmol/L for 36 h. RAECs were also pre-treated with carbachol or arecoline to examine their effects. RT-PCR was used to assess changes in the gene expression related to cell apoptosis.

RESULTSIncubation of RAECs with homocysteine at the concentration of 2.7 mmol/L resulted in morphologic changes, such as cellular shrinkage, membrane blebbing, chromatin condensation and margination. These could be attenuated by pretreatment with carbachol and arecoline at the concentration of 10 micromol/L for 12 h. Homocysteine induced apoptosis in RAECs and the molecular mechanisms were associated with the regulation of fas, fas-L and caspase-8 in the death receptor pathway, bcl-2, bcl-xL and bax in the mitochondrial pathway, caspase-12 in the endoplasmic reticulum pathway and caspase-3, caspase-6 and p53 as downstream effectors. Carbachol and arecoline attenuated the effects of homocysteine on genes in the death receptor pathway, in the mitochondrial pathway and in the downstream pathway. Atropine could reverse all of the effects of arecoline.

CONCLUSIONActivation of NNMR by carbacol and arecoline inhibits homocysteine-induced endothelial cell apoptosis mainly through regulation of death receptor pathway, mitochondrial pathway and downstream effectors.

Animals ; Aorta ; cytology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Arecoline ; Carbachol ; Cell Cycle ; Endoplasmic Reticulum ; metabolism ; Endothelial Cells ; cytology ; drug effects ; Homocysteine ; adverse effects ; Mitochondria ; metabolism ; Rats ; Receptors, Muscarinic ; metabolism