The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

Nitric oxide removal from flue gas coupled with the Fe^(Ⅱ)EDTA regeneration by ultraviolet irradiation

During wet complexation denitrification of flue gas,Fe^(Ⅱ)EDTA regeneration,also known as reducing Fe^(Ⅱ)EDTA and Fe^(Ⅱ)EDTA-nitric oxide(NO)to Fe^(Ⅱ)EDTA,is crucial.In this paper,ultraviolet(UV)light was used for the first time to reduce Fe^(Ⅱ)EDTA-NO.The experimental result demonstrated that Fe^(Ⅱ)EDTA-NO reduction rate increased with UV power increasing,elevated temperature,and initial Fe^(Ⅱ)EDTA-NO concentration decreasing.Fe^(Ⅱ)EDTA-NO reduction rate increased first and then decreased as pH value increased(2.0-10.0).Fe^(Ⅱ)EDTA-NO reduction with UV irradiation presented a first order reaction with respect to Fe^(Ⅱ)EDTA-NO.Compared with other Fe^(Ⅱ)EDTA regeneration methods,Fe^(Ⅱ)EDTA regeneration with UV show more superiority through comprehensive consideration of regeneration rate and procedure.Subsequently,NO absorption experiment by Fe^(Ⅱ)EDTA solution with UV irradiation confirmed that UV can significantly promote the NO removal performance of Fe^(Ⅱ)EDTA.Appropriate oxygen concentration(3%(vol))and acidic environment(pH=4)was favorable for NO removal.With UV power increasing as well as temperature decreasing,NO removal efficiency rose.In addition,the mechanism research indicates that NO from flue gas is mostly converted to NO_(2)-,NO_(3)-,NH_(4)^(+),N_(2),and N_(2)O with Fe^(Ⅱ)EDTA absorption liquid with UV irradiation.UV strengthens NO removal in Fe^(Ⅱ)EDTA absorption liquid by forming a synergistic effect of oxidation-reduction-complexation.Finally,compared with NO removal methods with Fe^(Ⅱ)EDTA,Fe^(Ⅱ)EDTA combined UV system shows prominent technology advantage in terms of economy and secondary pollution.

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)implants.There is a need to explore more effective approaches for the treatment of MRSA biofilm infections.Methods:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@SNP-OGP.The physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release behavior.The synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid leakage.Fluorescence staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture system.Giemsa staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in vivo.Results:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and causing leakage of intracellular components(P<0.01).In vitro experiments revealed that Ti-PDA@SNP-OGP not only facilitated osteogenic differentiation of MSCs,but also promoted the polarization of pro-inflammatory M1 macrophages to the anti-inflammatory M2-phenotype(P<0.05 or P<0.01).The favorable osteo-immune microenvironment further facilitated osteogenesis of MSCs and the anti-inflammation of RAW264.7 cells via multiple paracrine signaling pathways(P<0.01).In vivo evaluation confirmed the aforementioned results and revealed that Ti-PDA@SNP-OGP induced ameliorative osseointegration in an MRSA-infected femoral defect implantation model(P<0.01).Conclusions:Ti-PDA@SNP-OGP is a promising multi-functional material for the high-efficient treatment of MRSA infections in implant replacement surgeries.

Carbon Monoxide Modulates Auxin Transport and Nitric Oxide Signaling in Plants under Iron Deficiency Stress

Carbon monoxide(CO)and nitric oxide(NO)are signal molecules that enhance plant adaptation to environmental stimuli.Auxin is an essential phytohormone for plant growth and development.CO and NO play crucial roles in modulating the plant’s response to iron deficiency.Iron deficiency leads to an increase in the activity of heme oxygenase(HO)and the subsequent generation of CO.Additionally,it alters the polar subcellular distribution of Pin-Formed 1(PIN1)proteins,resulting in enhanced auxin transport.This alteration,in turn,leads to an increase in NO accumulation.Furthermore,iron deficiency enhances the activity of ferric chelate reductase(FCR),as well as the expression of the Fer-like iron deficiency-induced transcription factor 1(FIT)and the ferric reduction oxidase 2(FRO2)genes in plant roots.Overexpression of the long hypocotyl 1(HY1)gene,which encodes heme oxygenase,or the CO donor treatment resulted in enhanced basipetal auxin transport,higher FCR activity,and the expression of FIT and FRO2 genes under Fe deficiency.Here,a potential mechanism is proposed:CO and NO interact with auxin to address iron deficiency stress.CO alters auxin transport,enhancing its accumulation in roots and up-regulating key iron-related genes like FRO2 and IRT1.Elevated auxin levels affect NO signaling,leading to greater sensitivity in root development.This interplay promotes FCR activity,which is crucial for iron absorption.Together,these molecules enhance iron uptake and root growth,revealing a novel aspect of plant physiology in adapting to environmental stress.

Operation room nursing based on humanized nursing mode combined with nitric oxide on rehabilitation effect after lung surgery

BACKGROUND With advancements in the diagnosis and treatment of lung diseases,lung segment surgery has become increasingly common.Postoperative rehabilitation is critical for patient recovery,yet challenges such as complications and adverse outcomes persist.Incorporating humanized nursing modes and novel treatments like nitric oxide inhalation may enhance recovery and reduce postoperative complications.AIM To evaluate the effects of a humanized nursing mode combined with nitric oxide inhalation on the rehabilitation outcomes of patients undergoing lung surgery,focusing on pulmonary function,recovery speed,and overall treatment costs.METHODS A total of 79 patients who underwent lung surgery at a tertiary hospital from March 2021 to December 2021 were divided into a control group(n=39)receiving a routine nursing program and an experimental group(n=40)receiving additional humanized nursing interventions and atomized inhalation of nitric oxide.Key indicators were compared between the two groups alongside an analysis of treatment costs.RESULTS The experimental group demonstrated significant improvements in pulmonary function,reduced average recovery time,and lower total treatment costs compared to the control group.Moreover,the quality of life in the experimental group was significantly better in the 3 months post-surgery,indicating a more effective rehabilitation process.CONCLUSION The combination of humanized nursing mode and nitric oxide inhalation in postoperative care for lung surgery patients significantly enhances pulmonary rehabilitation outcomes,accelerates recovery,and reduces economic burden.This approach offers a promising reference for improving patient care and rehabilitation efficiency following lung surgery.

Effects of Nitric Oxide on the Germination of Wheat Seeds and Its Reactive Oxygen Species Metabolisms Under Osmotic Stress

Effects of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on the germination and metabolism of reactive oxygen species were surveyed in wheat (Triticum aestivum L.) seeds. Germination of wheat seeds and even the elongation of radicle and plumule were dramatically promoted by SNP treatments during the germination under osmotic stress. Meanwhile, activities of amylase and EP were enhanced, thus leading to the degradation of storage reserve in seeds. After osmotic stress was removed, higher viability of wheat seeds was also maintained. In addition, the activities of CAT, APX and the content of proline were increased by SNP treatment simultaneously, but activities of LOX were inhibited, and both of which were beneficial for improving the antioxidant capacity during the germination of wheat seeds under osmotic stress. It was also shown that the increase of the activity of amylase induced by SNP in embryoless half-seeds of wheat in the beginning period of germination (6 h) might be indirectly related to GA(3).

Regulation of Nitric Oxide on the Aging Process of Wheat Leaves

When the first fully expanded leaf of wheat ( Triticum aestivum L.) seedlings with two leaves were treated with different concentrations (0.05, 0.10, 0.20 and 0.50 mmol/L) of nitric oxide donor, sodium nitroprusside (SNP), the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA) were reduced by the lower concentrations (0.05, 0.10 and 0.20 mmol/L), but enhanced by the higher concentration of SNP (0.50 mmol/L). The protective effect of 0.10 mmol/L SNP was the most obvious. Furthermore, the treatment with 0.10 mmol/L SNP on the above seedlings until the fourth leaves were fully expanded attenuated the accumulation of H2O2, superoxide anion radical (O-2(-)) and MDA, also counteracted the degradation of chlorophyll and soluble proteins, especally Rubisco, both leading to the effective delay of aging process in wheat leaves. The effects of different SNP concentrations (0.05, 0.10, 0.20, 0.50, 1.00 and 5.00 mmol/L) also displayed a dual role in an aging experiment of chloroplasts in vitro, one of which, 0.2 mmol/L SNP treatment, protected the membrane structure and attenuated the degradation of Rubisco effectively. Based on the present results, it was inferred that lower concentrations of nitric oxide (NO) might play a role in delaying aging process in wheat leaves, i.e., might attribute to decrease the level of reactive oxygen species (ROS) and the alleviation of further oxidative damage caused by ROS.

Experimental studies on photocatalytic oxidation of nitric oxides using titanium dioxide

In order to remove nitric oxides （NO） from flue gas, experimental studies on the photocatalytic oxidation （PCO） of NO are carried out in an efficient laboratory-scale reactor. Nano-sized TiO2 particles loading on quartz sand are prepared and used as the photocatalyst. Effects of several key operating parameters on NO conversion are investigated, including operating temperature, NO inlet concentration, oxygen percentage, relative humidity and residence time. The results illustrate that the NO inlet concentration, the oxygen percentage and the relative humidity play an important role in the oxidation of NO. A lower NO inlet concentration and a higher oxygen percentage result in a higher NO conversion efficiency. When the relative humidity is 8%, the maximum value of NO conversion efficiency is achieved. In addition, the operating temperature and the residence time have a little effect on the conversion efficiency of NO.

Effects of Exogenous Nitric Oxide on Membrane Lipid Peroxidation in Wheat Seeding Exposed to Enhanced Ultraviolet-B Radiation

[Objective] Effects of different concentrations of nitric oxide on membrane lipid peroxidation of wheat induced by enhanced UV-B radiation were researched,sodium nitroprusside （SNP） was selected as an exogenous nitric oxide（NO）donor.[Method] There are 3 groups including CK,UV treatment group （B）,B＋SNP treatment group,0,1,2,3,4 d sampling after treatment respectively,and physiological and biochemical indexes of MDA content and CAT,POD,SOD and so on were determined,repeated 3 times,and statistical analyzed.[Result] The results showed that,after the enhanced UV-B radiation,activity of the catalase （CAT）,superoxide dismutase （SOD） and of the guaiacol peroxidase （POD） all reduced apparently,and the concentration of malondialdehyde （MDA） increased obviously,leading to oxidative damage in wheat seedlings.Impose different concentrations of SNP after UV-B radiation,may mitigate oxidative damage of wheat seedling from different degrees,which was in agreement with the effect of making the concentration of MDA decrease and the activity of the CAT,SOD and POD all increased.The mitigation role of 0.01 mol/L SNP was more obvious for roots＇ oxidative damage,while 0.1 mmol/L SNP is more effective for oxidative damage of leaves.[Conclusion] Exogenous NO donor SNP had obvious relieve effects on oxidative damage of wheat seedlings caused by UV-B radiation,which can enhance adaptive capacity of plants to adversity stress.

Effect of nitric oxide on the expression of apelin receptor mRNA in rat caudate nucleus

Objective To investigate the effect of nitric oxide （NO） on the expression of apelin receptor mRNA, as well as their correlation, in the caudate nucleus of rat. Methods L-Arginine （L-Arg）, N^G-nitro-L-arginine methyl ester （L-NAME） and normal saline （NS） was separately microinjected into rat caudate nucleus. Expressions of neuronal NO synthase （nNOS） mRNA and apelin receptor mRNA were detected by RT-PCR at 4, 8, 12, 24 and 48 h after microinjection, and their correlation was determined. Results The expressions of nNOS mRNA and apelin receptor mRNA were both significantly increased after microinjection of L-Arg, but significantly decreased after microinjection of L-NAME compared with the NS control group. The nNOS mRNA had a positive correlation with the expression of apelin receptor mRNA after microinjection of L-Arg and L-NAME. Conclusion The activity of NOS in the central nervous system, especially in the caudate nucleus, is one of the key factors for NO to exert many kinds of biological actions, such as modulation of central pain, as a neurotransmitter. The neurobiological action of NO in rat caudate nucleus may be associated with apelin receptors.

Differential Expression of PKC Isoforms and Their Tumoricidal Activity in Two Macrophage Cell Lines: Involvement of Nitric Oxide-dependent Mechanisms

Objective: To investigate the role of PKC isoforms in the regulation of LPS-triggered tumoricidal activity in macrophages and further elucidate its signal mechanisms. Methods: Two macrophage cell lines (P388D1 and RAW264.7) were stimulated by LPS alone, or with long-term of PMA pretreatment. Then cytotoxicities to P815 cells (by MTT assay) and IL-1, TNF- (by ELISA) and nitric oxide (NO) production (by Griess reagent) in supernatants were measured. Western blot for PKC isoforms after long-term PMA pretreatment was analyzed. Results: RAW264.7 cells were stimulated with LPS to kill target tumor cells P815, whereas P388D1 cells failed to develop such an ability. Down-regulation of PKC isoforms by chronic treatment with PMA significantly inhibited the LPS-induced cytotoxicity in RAW264.7 cells. In unstimulated state, Western blotting with rabbit antiserum specific for the PKC, 1, 2, or showed all 5 isoforms were detected in P388D1 cells, while only PKC, PKC1 and PKC were detected in RAW264.7 cells. Exposure of the cells to long-term of PMA treatment significantly down-regulated the expression of PKC, PKC1 and PKC in RAW264.7 cells. But in P388D1 cells, although PKC, PKC and PKC were down-regulated, the expression of PKC1 and PKC2 could not be regulated. Comparing with LPS-induced IL-1, TNF- and NO production by the two macrophage cell lines, P388D1 failed to produce NO. In RAW264.7 cells, LPS-induced NO production and antitumor activity was attenuated by the addition of L-NAME, an iNOS inhibitor. Conclusion: The results indicated a critical role of PKC in LPS-induced antitumor activity and this cytotoxicity is mainly due to PKC- mediated NO production by RAW264.7 cells, but not a direct cytotoxic activity.

Effects of Nerve Growth Factor on NMDA Receptor 1 and Neuronal Nitric Oxide Production after Spinal Cord Injury in Rats

Objective:To explore the protective mechanisms of nerve growth factor (NGF) on spinal cord injury (SCI) and provide theoretical basis for its clinical application. Methods: The SCI of Wistar rats was done by Allens weight dropping way by a 10 g×2.5 cm impact on the posterior of spinal cord T 8. NGF (3 g/L, 20 μl) or normal saline was injected through catheter into subarachnoid space 2, 4, 8, 12 and 24 h after SCI. The expression of N-methyl-D-asparate receptor 1 (NMDAR 1) and neuronal constitutive nitric oxide synthase (ncNOS) mRNA in rat spinal cord was detected by in situ hybridization. Results: Abnormal expression of NMDAR 1 and ncNOS mRNA appeared in spinal ventral horn motorneuron in injured rats, as compared with that in control group. The expression of NMDAR 1 and ncNOS mRNA in NGF group was significantly lower than that in saline group (P<0.01). Conclusion: NGF can protect spinal cord against injury in vivo. One of the mechanisms is that NGF can prohibit NMDAR 1 and nitric oxide (NO) production after spinal cord injury.

Association of Glu298Asp Polymorphism of the En-dothelial Nitric Oxide Synthase Gene with Essential Hypertension in Elderly People

Objective: To investigate the association of Glu298Asp polymorphism of theeNOS gene with essential hypertension in elderly people. Methods: Ninety-five cases of essentialhypertension were randomly chosen from outpatients and inpatients as the study group, and an equalnumber of sexes, age-matched healthy people as the control group. Their height, weight and bloodpressure were recorded and their fasting plasma lipid concentrations were measured. Glu298Asppolymorphism of the eNOS gene was measured using the methods of PCR and RFLP. Results: Theconstituent ratio of Genotype Glu/Asp in the study group (26.3%) was higher than that in the controlgroup (12.6%, x^2 = 5. 67, P<0.05), the allelic frequency of 298Asp in the study group (13.2%) wassignificantly higher than that in the control group (6.3%, x^2 = 5.06, P<0.05). Conclusion: Glu298Asp variant of the eNOS gene may be an independent predictor in essential hypertension.

Nitric Oxide Production is Involved in Inhibition Growth of Salicylate at Chilling Temperature

[Objective] The aim was to investigate whether NO is involved in the inhibitory effect of salicylic acid on the growth at low temperature in Arabidopsis.[Method] The endogenous NO level in roots of wild-type and NahG mutant growing at 22 or 4 ℃ was measured with NO-specific probe DAF-FM DA staining method.[Result] NO level in plants growing at 4 ℃ for a long term could be increased with time;low temperature could induce NO production in wild-type and NahG mutant,and the NO level in NahG mutant with low level of salicylic acid was significantly lower than that in wild-type.[Conclusion] NO was involved in the inhibitory effect of salicylic acid on the growth of Arabidopsis at low temperature.

Promotional effect of spherical alumina loading with manganese-based bimetallic oxides on nitric-oxide deep oxidation by ozone

Nitric oxide （NO） deep oxidation to dinitrogen pentoxide （N2O5） by ozone together with wet scrub-bing has become a promising technology for nitrogen-oxide （NOx） removal in industrial boilers. Catalysts were introduced to enhance the N2O5 formation rate with less ozone injection and leakage. A series of monometallic catalysts （manganese, cobalt, cerium, iron, copper, and chromium） as pre-pared by the sol-gel method were tested. The manganese oxides achieved an almost 80% conver-sion efficiency at an ozone （O3）/NO molar ratio of 2.0 in 0.12 s. The crystalline structure and porous parameters were determined. The thermodynamic reaction threshold of NO conversion to N2O5 is oxidation with an O3/NO molar ratio of 1.5. Spherical alumina was selected as the support to achieve the threshold, which was believed to improve the catalytic activity by increasing the surface area and the gas-solid contact time. Based on the manganese oxides, cerium, iron, chromium, cop-per, and cobalt were introduced as promoters. Cerium and iron improved the deep-oxidation effi-ciency compared with manganese/spherical alumina, with less than 50 mg/m3 of outlet NO ＋ nitro-gen oxide, and less than 25 mg/m3 of residual ozone at an O3/NO molar ratio of 1.5. The other three metal oxides inhibited catalytic activity. X-ray diffraction, nitrogen adsorption, hydrogen tempera-ture-programmed reduction, and X-ray photoelectron spectroscopy results indicate that the cata-lytic activity is affected by the synergistic action of NOx oxidation and ozone decomposition.

Enhanced visible-light photo-oxidation of nitric oxide using bismuth-coupled graphitic carbon nitride composite heterostructures

Pure bismuth（Bi） metal-modified graphitic carbon nitride（g-C3N4） composites（Bi-CN） with a pomegranate-like structure were prepared by an in situ method.The Bi-CN composites were used as photocatalysts for the oxidation of nitric oxide（NO） under visible-light irradiation.The inclusion of pure Bi metal in the g-C3N4 layers markedly improved the light absorption of the Bi-CN composites from the ultraviolet to the near-infrared region because of the typical surface plasmon resonance of Bi metal.The separation and transfer of photogenerated charge carriers were greatly accelerated by the presence of built-in Mott-Schottky effects at the interface between Bi metal and g-C3N4.As a result,the Bi-CN composite photocatalysts exhibited considerably enhanced efficiency in the photocatalytic removal of NO compared with that of Bi metal or g-C3N4 alone.The pomegranate-like structure of the Bi-CN composites and an explanation for their improved photocatalytic activity were proposed.This work not only provides a design for highly efficient g-C3N4-based photocatalysts through modification with Bi metal,but also offers new insights into the mechanistic understanding of g-C3N4-based photo catalysis.

Ginkgo biloba extract(EGb 761) attenuates lung injury induced by intestinal ischemia/reperfusion in rats:Roles of oxidative stress and nitric oxide

AIM： To investigate the effect of ginkgo biloba extract （EGb 761） on lung injury induced by intestinal ischemia/ reperfusion （ Ⅱ/R）. METHODS： The rat model of Ⅱ/R injury was produced by damping the superior mesenteric artery for 60 min followed by reperfusion for 180 min. The rats were randomly allocated into sham, Ⅱ/R, and EGb ＋Ⅱ/R groups. In EGb ＋Ⅱ/R group, EGb 761 （100 mg/kg per day） was given via a gastric tube for 7 consecutive days prior to surgery. Rats in Ⅱ/R and sham groups were treated with equal volumes of the vehicle of EGb 761. Lung injury was assessed by light microscopy, wet-todry lung weight ratio （W/D） and pulmonary permeability index （PPT）. The levels of malondialdehyde （MDA） and nitrite/nitrate （NO2/NO3）, as well as the activities of superoxide dismutase （SOD） and myeloperoxidase （MPO） were examined. Western blot was used to determine the expression of inducible nitric oxide synthase （iNOS）. RESULTS： EGb 761 markedly improved mean arterial pressure and attenuated lung injury, manifested by the improvement of histological changes and significant decreases of pulmonary W/D and PPT （P 〈 0.05 or 0.01）.Moreover, EGb 761 markedly increased SOD activity, reduced MDA levels and MPO activity, and suppressed NO generation accompanied by down-regulation of iNOS expression （P 〈 0.05 or 0.01）. CONCLUSION： The results indicate that EGb 761 has a protective effect on lung injury induced by Ⅱ /R, which may be related to its antioxidant property and suppressions of neutrophil accumulation and iNOS- induced NO generation. EGb 761 seems to be an effective therapeutic agent for critically ill patients with respiratory failure related to Ⅱ/R.

A study on relationship of nitric oxide,oxidation,peroxidation,lipoperoxidation with chronic cholecystitis

AIM:To study relationship of injury induced by nitric oxide, oxidation, peroxidation,lipoperoxidation with chronic cholecystitis.METHODS:The values of plasma nitric oxide (P-NO), plasma vitamin C (P-VC), plasma vitamin E (P-VE), plasma beta-carotene (P-beta-CAR), plasma lipoperoxides (P-LPO), erythrocyte superoxide dismutase (E-SOD), erythrocyte catalase (E-CAT), erythrocyte glutathione peroxidase (E-GSH-Px) activities and erythrocyte lipoperoxides (E-LPO) level in 77 patients with chronic cholecystitis and 80 healthy control subjects were determined, differences of the above average values between the patient group and the control group and differences of the average values between preoperative and postoperative patients were analyzed and compared, linear regression and correlation of the disease course with the above determination values as well as the stepwise regression and correlation of the course with the values were analyzed.RESULTS:Compared with the control group, the average values of P-NO, P-LPO, E-LPO were significantly increased (P【0.01), and of P-VC, P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px decreased (P 【0.01) in the patient group. The analysis of the linear regression and correlation showed that with prolonging of the course, the values of P-NO, P-LPO and E-LPO in the patients were gradually ascended and the values of P-VC,P-VE, P-beta-CAR, E-SOD, E-CAT and E-GSH-Px descended (P【0.01). The analysis of the stepwise regression and correlation indicated that the correlation of the course with P-NO, P-VE and P-beta-CAR values was the closest. Compared with the preoperative patients, the average values of P-NO, P-LPO and E-LPO were significantly decreased (P 【0.01) and the average values of P-VC, E-SOD, E-CAT and E-GSH-Px in postoperative patients increased (P 【0.01) in postoperative patients. But there was no significant difference in the average values of P-VE, P-beta-CAR preoperative and postoperative patients.CONCLUSION:Chronic cholecystitis could induce the increase of nitric oxide, oxidation, peroxidation and lipoperoxidation.

Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma:Correlation with microvessel density

AIM:Cydooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins.Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms.The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis,tumorigenesis and inflammatory processes.This study was to clarify their role in pancreatic adenocarcinomas. METHODS:We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocardnomas of different grade and stage.The results were compared with microvessel density and dinicopathological data. RESULTS:Twenty-one (52.5%) of the cases showed iNOS expression,15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors.Staining intensity was different between the tumors.No correlation between iNOS and COX-2 expression was seen.There was no relationship with microvessel density. However,iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression.There was no correlation with other clinicopathological data. CONCLUSION:Approximately half of the cases expressed iNOS and COX-2.These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas.Due to a low prevalence of COX-2 expression,chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success.

Effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats

AIM: To investigate the effect of L-NAME on nitric oxide and gastrointestinal motility alterations in cirrhotic rats. METHODS: Rats with cirrhosis induced by carbon tetrachloride were randomly divided into two groups, one n =13 receiving 0.5mg.kg(-1) per day of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, for 10 days, whereas the other group (n =13) and control (n =10) rats were administrated the same volume of 9g.L(-1) saline. Half gastric emptying time and 2h residual rate were measured by SPECT, using (99m)Tc-DTPA-labeled barium sulfate as test meal. Gastrointestinal transition time was recorded simultaneously. Serum concentration of nitric oxide (NO) was determined by the kinetic cadmium reduction and colorimetric methods. Immunohistochemical SABC method was used to observe the expression and distribution of three types of nitric oxide synthase (NOS) isoforms in the rat gastrointestinal tract. Western blot was used to detect expression of gastrointestinal NOS isoforms. RESULTS: Half gastric emptying time and trans-gastrointestinal time were significantly prolonged(124.0 +/- 26.4 min; 33.7 +/- 8.9 min; 72.1 +/- 15.3 min; P【0.01), (12.4 +/- 0.5h; 9.5 +/- 0.3h; 8.2 +/- 0.8h; P【0.01), 2h residual rate was raised in cirrhotic rats than in controls and cirrhotic rats treated with L-NAME (54.9 +/- 7.6%,13.7 +/- 3.2%, 34.9 +/- 10.3%, P【0.01). Serum concentration of NO was significantly increased in cirrhotic rats than in the other groups (8.20 +/- 2.48) micromol.L(-1), (5.94 +/-1.07) micromol.L(-1) and control (5.66 +/- 1.60 micromol.L(-1), P【0.01. NOS staining intensities which were mainly located in the gastrointestinal tissues were markedly lower in cirrhotic rats than in the controls and cirrhotic rats after treated with L-NAME. CONCLUSION: Gastrointestinal motility was remarkably inhibited in cirrhotic rats, which could be alleviated by L-NAME. Nitric oxide may play an important role in the inhibition of gastrointestinal motility in cirrhotic rats.