Nitric oxide (NO), which is involved in the regulation of the cardiovascular system, nervous system, immune system, reproductive system, digestive system and other physiological activities, is an important biological substance with activity. Under normal physiological conditions, neuronal nitric oxide synthase (nNOS) can precisely regulate the nervous system NO production, release, diffusion and inactivation processes. But an excess of NO associates with the development of cerebral ischemia, Alzheimer's and Parkinson's psychosis nervous system diseases, while inhibition of nNOS activity can regulate the content of NO in vivo, and produce a therapeutic effect on some of the nervous system diseases. This review mainly describes the structure and regulation of nNOS and recent developments of small molecule inhibitors of nNOS.
Alzheimer Disease ; physiopathology ; Brain Ischemia ; physiopathology ; Humans ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type I ; antagonists & inhibitors ; metabolism ; Parkinson Disease ; physiopathology

Objective To observe the effects of methionine enkephalin (M-Enk) on migration of macrophages from mice with impaired liver and its immunomodulatory mechanisms. MethodsLiver of mice was impaired by feeding CCl4 and macrophage migration inhibitory factor (MMIF) was produced by Con A-stimulated spleen lympho- cytes. Inhibition of macrophage migration was measured in reaction system by adding M-Enk. Results Migration of macrophages in both liver-impaired and control group were suppressed by MMIF, but the suppression might be re- versed by adding 1 μmol/L M-Enk (P＜0. 05). M-Enk could significantly inhibit in vitro both of the combination of MMIF with macrophages and production of MMIF from lymphocytes (P＜0. 01). Macrophages from liver-imparied group showed a higher sensitivity compared to the control group (P＜0. 05). ConclusionThe study suggests that opi- oid peptieds play an important role in the modulation of the immune response under stress as liver impairment.

To prepare cyclosporine A (CyA) loaded block copolymer micelles and observe its release behaviors in vitro and pharmacokinetics in rats, methoxylpoly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (mPEG-PLGA) was synthesized by ring-opening copolymerization of lactide and glycolide in the presence of methoxylpoly (ethylene glycol) (mPEG) as initiator. The structure of the mPEG-PLGA copolymer was confirmed with 1H NMR and FT-IR. The cyclosporine A loaded micelles (CyA-PM) were prepared by solvent evaporation method and their morphology was observed by the transmission electron microscope (TEM). The mean size and size distribution were determined by dynamic light scattering (DLS). The release behaviors in vitro and pharmacokinetics in rats were investigated by HPLC method using cyclosporine A injection commercial agent, sandimmune, as the reference. The obtained CyA-PM showed spherical shape with the core-shell structure, the mean particle sizes are in the range of 136.1-141.9 nm. The drug loading amount and entrapment efficiency were increased and the particle size became smaller with decreasing the ratio of acetone to water. With the increasing of the amount of cyclosporine A fed the drug loading increased, entrapment efficiency decreased and the particle size had no change. CyA-PM showed significant sustained release behave in vitro compared with sandimmune and only 9.7% of encapsulated cyclosporine A was released after 12 hours, the release characteristics was well fitted with Higuchi equation (r = 0.999). The Pharmacokinetics study at equal administration dosage (5 mg x kg(-1)) in rats showed the half-life (t1/2) of CyA-PM extended and the area under concentration-time curve (AUC) increased compared to sandimmune. The results also showed that cyclosporine A concentration-time data were all in accord with two compartment model. Cyclosporine A loaded mPEG-PLGA micelles showed obviously solubility enhancement, sustained release and overcome the side effect and toxicity of sandimmune resulted from solubiling agent-polyoxyethylene castor oil (Cremophor EL) and might be developed as a novel dosage form of cyclosporine A.
Animals ; Area Under Curve ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Drug Carriers ; administration & dosage ; pharmacokinetics ; Drug Compounding ; Half-Life ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Male ; Micelles ; Particle Size ; Polyesters ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Polyethylene Glycols ; administration & dosage ; chemical synthesis ; pharmacokinetics ; Polymers ; administration & dosage ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Objective To evaluate the safety and efficacy of CT fluoroscopic guidance percutaneous acetic acid injection(PAI)tumor ablation and TACE for the malignant liver tumor.Methods PAI had been performed after TACE on 78 patients with malignant tumor(hepatocellular carcinoma 70,metastatic adenocarcinoma 8)since May 2005 to June 2007 in Southwest Hospital.All procedures were performed under CT fluoroscopic guidance.According to the different size of lesions,50%-60% acetic acid 2-10ml was injected into the lesions.PAI was repeated once or twice in some lesions based on the imaging.Results The needle could reach targets under CT real time fluoroscopy in all patients.No complication occurred,but with only moderate pain in 42 cases.The size of tumors shrank in 32 cases,remained unchanged 38 cases,and increased in 8 cases.The efficiency was 90%.All 78 patients were followed up for 3 months with all survival and 48 patients for 1 year with 40 survival.Conclusions CT fluoroscopic guidance PAI tumor ablation combined with TACE in the treatment of malignant liver tumor is safe and effective.(J Intervent Radiol,2007, 16:831-833)

OBJECTIVETo investigate the expression of the CDH13 gene and BCR/ABL fusion gene in chronic myeloid leukemia(CML) patients at different stages and explore their relationship.

METHODSRNA was isolated from peripheral blood in 30 healthy adults, 22 primary CML patients and 25 blastic crisis of CML patients. We examined the expression of the CDH13 gene and BCR/ABL fusion gene using EVA Green real-time reverse transcriptase-polymerase chain reaction (RT-PCR).

RESULTSThe expression of the BCR/ABL fusion gene in the patients with blastic crisis CML was 4.72 folds as that of the patients with primary CML. The expression of the CDH13 gene in the primary and blastic crisis CML patients was significantly reduced to 36% and 25% of that in healthy controls, respectively. Moreover, negative correlation was found between the expressions of these two genes.

CONCLUSIONThe study showed that the reduction of the CDH13 expression at different clinical stage of CML may account for the defective cell adhesion in CML, and the expression of the CDH13 gene was probably down-regulated by the BCR/ABL fusion gene.

Adolescent ; Adult ; Aged ; Cadherins ; genetics ; Case-Control Studies ; Female ; Fusion Proteins, bcr-abl ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid ; genetics ; pathology ; Male ; Middle Aged ; Polymerase Chain Reaction

The clinical features, examination findings and gene results of the newborn diagnosed with congenital dysplasia by the ANK3 gene heterozygous mutation in the First Hospital of Jilin University were retrospectively analyzed.A female newborn at 10 minutes presented for postnatal asphyxia and 10 minutes after resuscitation.She had a special appearance, with little spontaneous breathing, no swallowing, extremely low muscular tension, and no primal reflexes.Amplitude integrated electroencephalogram(aEEG) suggested the burst suppression (BS) background activity, BS (+ ), lower boundary at 2 μV, upper boundary at 50 μV, no sleep awakening cycle, no convulsive seizure, and mechanical brush seen in the original electroencephalogram burst.Severe abnormal aEEG was detected.Gene results suggested 2 heterozygous mutations in the ANK3 gene [c.4183(exon33) C >G and c. 8239(exon37) C >T], which have not been previously reported.This case report for the first time reported the clinical phenotype of the ANK3 gene mutation in the newborn with congenital dysplasia.

OBJECTIVETo report the first case of transumbilical laparoendoscopic single-site surgery-assisted vaginal hysterectomy in South China, and discuss its feasibility and safety.

METHODSA 42-year-old woman with multiple myoma of the uterus underwent laparoendoscopic single-site surgery-assisted vaginal hysterectomy performed using a single multiple-channel port inserted through a solitary 2 cm upper umbilicus incision.

RESULTSThe total operative time was 3 h, and duration of the laparoendoscopic procedure was 2 h. The surgery was completed uneventfully without an additional port incision or transfer to open surgery. The intraoperative blood loss was 100 ml. Bowel peristalsis was recovered 3 days after the operation. The vaginal stump and abdominal incision healed smoothly without occurrence of vaginal bleeding.

CONCLUSIONWith the development of surgical instruments and improvement of the surgeons' skills, laparoendoscopic single-site surgery, due to its invasiveness, can be a promising approach to the management of gynecological disease including gynecological malignant tumors.

Adult ; Female ; Humans ; Hysterectomy, Vaginal ; methods ; Laparoscopy ; methods ; Leiomyoma ; surgery ; Uterine Neoplasms ; surgery

OBJECTIVETo establish the rat model of acute pulmonary embolism, and study the changes of vascular active substances in pulmonary embolism rats, and investigate the interventive effect of anticoagulant drugs on vascular active substances.

METHODSOne hundred and twenty-eight rats were randomly divided into four groups: control group, model group, low-molecular-weight heparin and warfarin treated group and rivaroxaban-treated group (n = 32 in each group). The method of autologous thrombosis was used to establish the animal model of acute pulmonary embolism. The animals were treated with saline or different anticoagulant drugs. The physiological and biochemical parameters were detected at different time points after embolization. The rats were killed after embolism of 24 h, 3 d, 5 d or 1 week respectively and the pathologic samples of lung tissues were collected to analyze the pulmonary pathological changes in different groups.

RESULTSRats in embolization group after blood clots injection showed shortness of breath, oral cyanosis; quicken heart rates and other symptoms. All embolization groups had pulmonary hypertension, the levels of type B natriuretic peptide (BNP) were increased significantly. The ratio of endothelin-1 (ET-1)/NO and thromboxane (TXB2) and prostacyclin (6-k-PGFla) were abnormal. After treated with effective anticoagulant drugs, the levels of BNP, ET-1, NO, TXB2 and 6-k-PGF1a were tended to the normal levels in the control group. The pulmonary hypertensions were gradually decreased. The efficacy of rivaroxaban on pulmonary embolism was the same as that of the low molecular weight heparin or warfarin.

CONCLUSIONAnticoagulation therapy can effectively improve endothelial function after pulmonary embolism, reduce pulmonary hypertension, and revise the increased BNP levels to normal levels. The efficacy of rivaroxaban is not inferior to that of low molecular weight heparin and warfarin.

Animals ; Anticoagulants ; pharmacology ; Disease Models, Animal ; Endothelin-1 ; metabolism ; Heparin, Low-Molecular-Weight ; pharmacology ; Hypertension, Pulmonary ; drug therapy ; metabolism ; Lung ; pathology ; Morpholines ; pharmacology ; Pulmonary Embolism ; drug therapy ; metabolism ; Rats ; Rivaroxaban ; Thiophenes ; pharmacology ; Warfarin ; pharmacology

Objective To evaluate the effect of comprehensive schistosomiasis control measures based on infection source control in plateau mountain areas of Yunnan Province. Methods From 2006 to 2004,four administrative villages were selected as test areas from plateau canyon and plateau basin endemic areas in Jindun Town,Heqing County,two villages each type,and the comprehensive control measures were implemented,including the examination and treatment of schistosomiasis,Oncomela?nia hupensis snail survey and control,health education,improving drinking water and lavatories,banning grazing,constructing sanitary pen of livestock,replacing cattle with machine,etc. The schistosome infection state and snail status in 2006 were treat?ed as the baseline information,and the effect of the comprehensive measures were evaluated. Results The infection rate of hu?man in plateau canyon areas decreased from 4.94%in 2006 to 0.06%in 2014,and that of livestock decreased from 1.11%to 0. In plateau basin areas,there was only 1 case of schistosomiasis found in Xiaolian Village in 2007,and no any other cases found in the other years,the infection rates of livestock dropped from 7.38%to 0. Compared with 2006,the snail areas in the two type areas decreased by 74.89%and 75.30%,respectively,meanwhile,the percentage of snail area,the occurrence rate of frames with snails,as well as the average density of living snails also decreased,and no infected snails were found since 2008. Xidian and Xinzhuang villages in plateau canyon area reached the criteria of schistosomiasis transmission controlled in 2009,and Xiao?lian and Kangfu villages in plateau basin reached the criteria of transmission interrupted in 2014. Conclusions The comprehen?sive schistosomiasis control measures based on infection source control can effectively control the endemic situation of schistoso? miasis in plateau areas of Yunnan Province. In the future,we should pay an equal attention to the infection sources control and snail control to consolidate and amplify the achievement of schistosomiasis control.

Objective To understand the status of water contact and labor practice of residents in plateau mountain schisto?somiasis endemic areas in Yunnan Province so as to provide the evidence for formulating the strategy of prevention and control of schistosomiasis in the next step of work. Methods A total of 412 residents aged 6-65 years old in 2 villages were randomly sampled and investigated with questionnaires for their water contacts and labor practices in plateau valley schistosomiasis endem?ic areas. Then the schistosome infection status of the residents was surveyed with the indirect hemagglutination assay IHA . Re?sults Among the 412 residents investigated the rate of water contact was 88.35% and the main causes of water contact were watering and swimming and playing. The percentages of residents who had schistosomiasis history were 1.16% 0.00%30.80% 3.85% and 0 in them who had swimming and playing water?contacts bathing watering washing hands and others respectively χ2=38.96 P<0.01 . The positives of IHA in the above?mentioned residents were 18.60% 0.00% 37.60%23.08% and 0 respectively χ2=12.61 P<0.05 . Conclusions The productive infested water contact is the main way of schistosome infection. Therefore the changes of labor practices and water contact of the residents are very important for the ef?fective prevention and control of schistosomiasis transmission.