AIM: To investigate the mechanism of proliferation effect induced by (R,R)-XY-10 and (S,S)-XY-10 on retinal pigmented epithelial cells(ARPE-19).METHODS: Human retinal pigmented epithelial cells(ARPE-19) and human umbilical vein endothelial cells (HUVECs) were used to investigate the effect of (R,R)-XY-10 and (S,S)-XY-10 on cell growth,and their mechanisms of proliferative action by using ERK、 AKT、PI3K、Protein kinase C (PKC)and Nitric oxide synthase (NOS) inhibitors.RESULTS: (R,R)-XY-10 and (S,S)-XY-10 dose-dependently increased ARPE-19 cell proliferation,but not on HUVECs. When treated with proliferative inhibitors,H7(5μmol/L)、hypericin(20μmol/L)、PD98059(2μmol/L)、LY294002(50μmol/L)、SH-5 (10μmol/L) and L-NAME (100μmol/L),the proliferative effect was reduced by H7、hypericin、PD98059 and LY294002,but not by SH-5 and L-NAME.CONCLUSION: (R,R)-XY-10 and (S,S)-XY-10 can induce cell proliferation through MAPK and PI3K dependent pathway. KEYWORDS: age-related macular degeneration; (R,R)-XY-10; (S,S)-XY-10; ARPE-19 cells; human umbilical vein endothelial cells; proliferation

Objective To compaire the physical characteristics of semen morphology before and after semen coagulation-liquefaction under microscope and understand the significance of these characteristics for the determination of semen liquefaction.Methods Semens were placed in sperm counting chamber immediately after collection.The morphological changes of the seminal gelatinous substance during liquefaction were observed under microscope and analyzed.Results Morphological changes during semen liquefaction can be clearly observed.Among 32 samples of semen,forward sperm progression and motility were (30.3?12.4)% and (45.0?14.9)%,(44.9?12.7)% and (59.0?15.3)%,before and after the liquefaction,respectively.The differences were statistically significant (t=-1.130,5.023,P0.05).Conclusions Microscopic observation of the seminal gelatinous substance is a simple and feasible method for objective measurement of sperm liquefaction.These findings suggest it may provide pathological significance on semen liquefaction abnormality in infertility clinic.

ObjectiveTo investigate influence of sedation and analgesia on stress reaction of post-cardiac surgery in infants with congenital heart disease.MethodsForty children with congenital heart disease were randomly divided into 2 groups after cardiac surgery.The analgesia group was given 0.5-2.0 ?g/(kg?h) fentanyl intravenous infusion in 20 children undergoing cardiovascular surgery.The control group was given 5-8 mg/(kg?dose) lbuprofen orally.Midaiolam 0.01-0.20 mg/(kg?h) was used in 2 groups for sedation by intravenous infusion or 0.05-0.10 mg/(kg?dose)by intravenous push intermittently.The effects and adverse effects of sedation and analgesia were observed on 2,8,24,48 h after surgery in each group.The levels of cortisol,growth hormone,insulin and blood glucose were measured,respectively.ResultsThere were significant differences in Ramsay,Comfort value on 2,8,24 h(Pa

Traditional non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors are among the most widely used drugs. However, their significant side effects in gastrointestinal and cardiovascular systems limited the use of these drugs. Recently, research and development of NO-donating NSAIDs (NO-NSAIDs) have become one of the most important strategies to reduce these side effects. NO-NSAIDs may exert a broad range of positive effects in terms of NO-mediated gastrointestinal and cardiovascular safety as well as comparable or increased anti-inflammatory, analgesic properties relative to NSAIDs. This review briefly deals with chemistry of NO-NSAIDs, more details are focused on biological significance, mechanism of action, and therapeutic potential of this novel class of drugs.
Acetaminophen ; analogs & derivatives ; chemistry ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; pharmacology ; Aspirin ; analogs & derivatives ; chemistry ; pharmacology ; Cardiotonic Agents ; pharmacology ; Cyclooxygenase Inhibitors ; adverse effects ; pharmacology ; Flurbiprofen ; analogs & derivatives ; chemistry ; pharmacology ; Gastrointestinal Diseases ; chemically induced ; prevention & control ; Humans ; Ibuprofen ; analogs & derivatives ; chemistry ; pharmacology ; Naproxen ; analogs & derivatives ; chemistry ; pharmacology ; Nitrates ; chemistry ; pharmacology ; Nitric Oxide Donors ; pharmacology

Animals ; Apoptosis ; drug effects ; Azo Compounds ; chemical synthesis ; pharmacology ; Cell Line, Tumor ; Drug Delivery Systems ; Humans ; Liver ; metabolism ; Liver Neoplasms ; pathology ; Nitrates ; chemical synthesis ; pharmacology ; Nitric Oxide Donors ; chemical synthesis ; pharmacology ; Oleanolic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology ; Piperazines ; chemical synthesis ; pharmacology ; Ursodeoxycholic Acid ; analogs & derivatives ; chemical synthesis ; pharmacology

Nitric oxide (NO) as a messenger and/or effector plays important roles in vivo. The decreased availability of NO or dysfunction in NO signaling has often been implicated in the development and progression of diseases, and design and research of NO-donating drugs has become one of the important strategies in drug discovery. In connection with authors' scientific practice, this article reviews the recent advances in the research of NO-donating drugs.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Aspirin ; analogs & derivatives ; pharmacology ; therapeutic use ; Azo Compounds ; pharmacology ; Cardiovascular Diseases ; drug therapy ; Cell Line, Tumor ; Drug Design ; Humans ; Neoplasms ; drug therapy ; pathology ; Nitrates ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; pharmacology ; therapeutic use ; Piperazines ; pharmacology ; Signal Transduction ; drug effects

BACKGROUNDMicrovascular Decompression (MVD) operation is the most reliable treatment for hemifacial spasm (HFS), but it causes many complications. The aim of this retrospective study was to investigate the factors relavent to the effects and postoperative complications of microvascular decompression on hemifacial spasm.

METHODSA total of 1200 HFS patients treated with MVD were studied retrospectively. The root exit zone (REZ) of the facial nerve was exposed through the infraflocculus approach, the offending vessels were identified and separated from the REZ, and a Teflon graft was interposed between the offending vessels and the brain stem. Brain stem auditory evoked potential (AEP) was monitored intraoperatively.

RESULTSThe offending vessels can be identified in all patients. The anteroinferior cerebellar artery was the main offending vessel (42.6%). Patients with vertebral artery compression had a multiple vascular compression fashion. Follow-up for 2 - 10 years (mean 4.2 years) showed that 88.7% patients were cured and 5.6% relieved, with an effective rate of 94.3%. Recurrence rate was 3.2%, and the ineffective rate was 2.6%. The most frequent complication was hearing dysfunction (2.8%).

CONCLUSIONSMVD is the most definitive treatment method of HFS. The key procedures of this operation include adequate exposure of the REZ, identification of the offending vessels, and proper positioning of Teflon grafts. Complications can be reduced effectively by utilizing a real-time AEP monitoring during the operation.

Adult ; Aged ; Decompression, Surgical ; adverse effects ; Female ; Hemifacial Spasm ; surgery ; Humans ; Male ; Microsurgery ; Middle Aged ; Postoperative Complications ; etiology ; Retrospective Studies

AIMTo search for new derivatives of diclofenac (DC) having higher potency than the parent drug and lacking its undesirable effects.

METHODSCoupling DC with NO donor 3-hydroxymethyl-4-phenylfuroxan and its isomer through esterification, evaluating anti-inflammatory and analgesic activities, observing side effects in the rat gastrointestinal (GI) tract and assessing NO releasing ability both in vitro and in vivo.

RESULTSFifteen new compounds including nine target ones (II1-9) were synthesized, and their structures were determined by IR, 1HNMR, MS and elemental analysis. Compounds II3 and II9 showed anti-inflammatory activity comparable to DC. Compound II2 showed stronger anti-inflammatory and analgesic activities and less GI side effect than DC, and released NO in vivo.

CONCLUSIONCompound II2 is worthy to be intensively studied.

Analgesics ; chemical synthesis ; pharmacology ; therapeutic use ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; chemical synthesis ; pharmacology ; therapeutic use ; Cyclic N-Oxides ; administration & dosage ; chemistry ; pharmacology ; Diclofenac ; chemical synthesis ; pharmacology ; therapeutic use ; Digestive System ; drug effects ; Edema ; drug therapy ; Gastrointestinal Hemorrhage ; chemically induced ; Mice ; Molecular Structure ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; chemistry ; pharmacology ; Oxadiazoles ; administration & dosage ; chemistry ; pharmacology ; Pain Threshold ; drug effects ; Rats ; Structure-Activity Relationship

AIMTo synthesize and study the antithrombotic activity of NO-donating aspirin derivatives.

METHODSFuroxans and nitrates were incorporated to aspirin via antioxidant ferulic acid as a linker, and the target compounds were screened for in vitro and in vivo inhibitory activities of platelet aggregation, and for inhibitory effect on A-V hypass thromhosis in rats.

RESULTSFourteen novel compounds I(1-14), were synthesized and their structures were confirmed Iy MS, IR, 1H NMR and elemental analysis. Biological screening results demonstrated that some tested compounds exhibited potential antithrombotic activ it.

CONCLUSIONAcetylsalicyl ferulic acid-coupling furoxans and nitrates might he used as a lead for further study.

Animals ; Aspirin ; chemistry ; Coumaric Acids ; chemistry ; Fibrinolytic Agents ; chemical synthesis ; chemistry ; pharmacology ; Models, Chemical ; Molecular Structure ; Nitrates ; chemistry ; Nitric Oxide Donors ; chemistry ; Oxadiazoles ; chemistry ; Platelet Aggregation ; drug effects ; Platelet Aggregation Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Rats