Biomedical subjects

S Y Kim

Publications and source records attributed to S Y Kim.

At least 91 records · Page 5Linked to original sources

PubMed2001

Group IIA secretory phospholipase A(2) stimulates inducible nitric oxide synthase expression via ERK and NF-kappaB in macrophages.

The mammalian group IIA secretory phospholipase A(2) (sPLA(2)) is believed to play an important role in inflammation and cell injury. The present study underlines the importance of group IIA sPLA(2) in the regulation of iNOS. Treatment of cells with sPLA(2) induced protein expression and mRNA accumulation of iNOS in a dose-dependent manner. The pretreatment of cells with rho-BPB or SCA, selective sPLA(2) inhibitors, inhibited sPLA(2)-induced iNOS expression. sPLA(2) stimulated the simultaneous activation of two classes of mitogen-activated protein kinases ERK and JNK, but did not stimulate p38 MAPK. PD98059, a selective MEK inhibitor, inhibited sPLA(2)-induced nitrite production and iNOS expression as well as ERK phosphorylation. In addition, pretreatment of rho-BPB or SCA also resulted in inhibition of sPLA(2)-induced ERK phosphorylation. The sPLA(2) signaling mechanisms involving the activation of transcription factor NF-kappaB were studied in the same cells. That stimulation of cells with sPLA(2) caused NF-kappaB activation in a time-dependent manner was shown by the detection of NF-kappaB-specific DNA-protein binding and by IkappaBalpha degradation. sPLA(2)-induced NF-kappaB activation was prevented in the presence of rho-BPB. Furthermore, the NF-kappaB inhibitor PDTC suppressed sPLA(2)-induced nitrite production and iNOS expression as well as IkappaBalpha degradation. The results strongly suggest that group IIA sPLA(2) induces iNOS in macrophages and that this induction occurs through ERK and NF-kappaB.

Animals↗

PubMed2001

Effects of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) on the expression of inflammatory cytokines and apoptosis induction in rheumatoid synovial fibroblasts and monocytes.

This study was performed to investigate whether peroxisome proliterator-activated receptor-gamma (PPAR-gamma) exerted an anti-inflammatory effect on rheumatoid synovial cells and inhibited dysregulated proliferation. The expression of PPAR-gamma mRNA in cultured human synoviocytes and THP-1 cells was analysed by RT-PCR. PPAR-gamma was expressed in normal, osteoarthritis (OA), rheumatoid arthritis (RA) synovial cells as well as a human monocytic cell line, THP-1. In RA and OA synoviocytes, the induction of inflammatory cytokine mRNA expression such as TNF-alpha and IL-1beta was significantly inhibited by the natural PPAR-gamma agonist, 15 deoxy-Delta(12,14)prostaglandin J(2)(15d-PGJ(2)). The effect of PPAR-gamma on the nuclear factor (NF)-kappaB activity was tested by electrophoretic mobility shift assay (EMSA). Both troglitazone and 15d-PGJ(2)markedly inhibited TNF-alpha-induced NF-kappaB activation at 30 microM. However, PPAR-gamma agonist neither reduced proliferation nor induced apoptosis in RA synoviocytes when measured by XTT assay and fluorescence activated cell sorter (FACS) analysis. In contrast, it induced apoptosis in a dose-dependent manner in THP-1 cells and augmented TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis as well. In conclusion, these data demonstrate that PPAR-gamma is expressed in human synoviocytes and THP-1 cells, and the PPAR-gamma activation inhibits expression of inflammatory cytokines in RA synoviocytes. Furthermore, PPAR-gamma activation induces apoptosis by itself and augments TRAIL/Apo2L-induced apoptosis in THP-1 cells. These results suggest that PPAR-gamma agonists may provide a new therapeutic approach for RA.

Apoptosis↗

PubMed2001

Source of errors in the evaluation of early rectal cancer by endoluminal ultrasonography.

PURPOSE: Although preoperative evaluation of early rectal cancers can be done by endoluminal sonography and by means of colonoscopic findings, it is still controversial whether endoluminal sonography can effectively discriminate mucosal from submucosal lesions. This study was performed to verify objective causes of errors in the evaluation of early rectal cancer (T0/1) using a review of videotaped endoluminal sonography images. METHODS: Eighty-nine patients with suspected early rectal cancer on endoluminal sonography were included. Two different scanners with appropriate probes were used according to tumor location, i.e., transrectal ultrasonography was used to scan up to 8 cm of the rectum above the anal verge, whereas endoscopic ultrasonography was used to assess higher lesions. Endoluminal sonography images were correlated with histologic infiltration and were reevaluated carefully to identify sources of errors. RESULTS: Sensitivity and specificity were 83.1 and 96.5 percent, respectively, for tumor staging, whereas sensitivity was very low compared with specificity (16.7 vs. 90.2 percent) for metastatic lymph nodes. Endoluminal sonography images showed irregularity of the underlying tumor border (P < 0.01) and hypoechoic blurring or cutoff of the inner and outer hypoechoic layers (P < 0.001), all of which closely correlated with histologic infiltration of tumor cells. Overstaging occurred more than twice as often as understaging in tumor reevaluation (14 vs. 5 occurrences). In contrast to tumors, lymph nodes showed a similar amount of both overstaging (four cases) and understaging (five cases). The sources of errors were summarized as five types: false instrumentation, interpretive errors, anatomic defects, imaging failure, and inevitable errors. CONCLUSIONS: Because false instrumentation, interpretive errors, and anatomic defects were considered preventable, 23 (82.1 percent) of the 28 errors might have been avoided. Therefore, a clear image by endoluminal sonography can effectively distinguish mucosal from submucosal lesions in early rectal cancer.

Diagnosis, Differential↗

PubMed2001

Two cases of large solitary fibrous tumors of the pleura associated with fasting hypoglycemia.

We describe two cases of elderly women who presented hypoglycemic episodes with suppressed levels of insulin and insulin-like growth factor I. They were found to have huge malignant solitary fibrous tumor of the pleura. The tumors had rich vascularization on enhanced CT scans and showed characteristic low signal intensity on T2-weighted MR images. This paraneoplastic hypoglycemia is caused by an incompletely processed precursor of insulin-like growth factor II secreted from the tumor. Hypoglycemia and insulin suppression were resolved after removal of the tumors.

Aged↗

PubMed2001

Radiologic changes of cervical spine in ankylosing spondylitis.

Ankylosing spondylitis (AS) is characterised by its effects on the axial skeleton. The cervical spine is also vulnerable to the disease process. Our aim was to determine the frequency of radiologic changes to the cervical spine and their correlation with clinical variables. We also used the Bath Ankylosing Spondylitis Radiology Index (BASRI) system, which is one of the reliable scoring systems of radiography, to score the global radiologic changes to the cervical and lumbar spine and the hip joints in our AS cohort. There were 181 patients with anteroposterior and lateral full-flexion views on radiography of the cervical spine here included in the study. A radiologist examined the radiologic changes to all anatomical compartments of the cervical spine in detail and graded them according to the BASRI system. We used the clinical and demographic data of our AS cohort to determine their relation to the radiographic changes. Eighty-eight patients (48.6%) showed radiological changes to the cervical spine; to the discovertebral joint 35.9%; the apophyseal joint 26.0%; atlantoaxial articulation 22.1% (atlantoaxial subluxation 13.8%); the costovertebral joint 18.2%; and to the posterior ligamentous attachment 11.6%. Using the BASRI system, 73 patients (40.3%) showed radiologic changes to the cervical spine and were graded as score 1 (1.7%), 2 (22.7%), 3 (6.6%) or 4 (9.4%). Among those graded as normal by the BASRI system, 17 showed some changes the cervical spine, such as atlantoaxial joint subluxation or narrowing, and severe osteoporosis with no other radiographic changes. Current age, disease duration, inflammatory back pain and cervical symptoms were associated with the radiographic changes to the cervical spine. The BASRI-cervical spine score correlated with the BASRI-lumbar spine and hip joint score, sacroiliitis, disease duration, and duration of inflammatory back pain and cervical symptoms. Our data suggest that radiographic changes to the cervical spine are frequent in AS, and can be predicted in the patients with old age, long duration of disease and inflammatory back pain, and cervical symptoms. Also, the BASRI scoring system showed similar results as a detailed assessment of the cervical spine in our study.

Adolescent↗

PubMed2001

Induction of remission with intravenous immunoglobulin and cyclophosphamide in steroid-resistant Evans' syndrome associated with dermatomyositis.

Evans' syndrome is characterised by the simultaneous or sequential occurrence of Coombs'-positive haemolytic anaemia (AIHA) and immune thrombocytopenia without underlying aetiology. It has been found to be associated with collagen vascular diseases, especially systemic lupus erythematosus (SLE) and scleroderma. However, Evans' syndrome with dermatomyositis is very rare. A 59-year-old woman, who had been taking high-dose prednisolone for a month and cyclosporin for 10 days for dermatomyositis, developed purpura on the left popliteal fossa. The platelet and haemoglobin levels decreased to 77,000/mm3 and 9.8 g/dl, respectively. Antiplatelet antibody was positive. Thrombocytopenia responded to intravenous immunoglobulin (IVIG) for a short time, but further decreased in a week. Her blood film showed features of haemolytic anaemia. Laboratory findings showed reticulocytosis and a positive direct Coombs' test. Bone marrow examination showed a mild hyperplasia of erythroid precursors and megakaryocytes. The patient was successfully treated with cyclophosphamide in addition to oral prednisolone. AIHA in connective tissue disease may develop gradually and show a benign clinical course in most patients. Therefore, we suggest that patients with dermatomyositis and anaemia should always be checked for haemolysis if there is no other explanation.

Anemia, Hemolytic, Autoimmune↗

PubMed2001

5-acyloxy-5-hydroxymethyltetrahydro-2-furancarboxylate as a novel template for protein kinase C (PKC) binding.

A series of alkyl tetrahydrofuran-2-carboxylates (1-4) bearing a new set of three pharmacophoric groups were tested as protein kinase C (PKC) ligands. The compounds were synthesized from commercially available glycidyl 4-methoxyphenyl ether. The correlation between their binding affinities for PKC-alpha and a conformational fit to phorbol ester indicates they mimic a pharmacophore model comprising the C20-OH, C3-C=O and C9-OH rather than that including the C13-C=O moiety.

Binding, Competitive↗

PubMed2001

Poly(ethylene glycol)-poly(L-lactide) diblock copolymer prevents aggregation of poly(L-lactide) microspheres during ethylene oxide gas sterilization.

Sterilization procedure is one of the most important obstacles in the clinical applications of biodegradable microspheres. The microspheres prepared with poly(alpha-hydroxy acid) were severely aggregated during ethylene oxide (EO) gas sterilization, and could not be used in clinical applications. In this study, the effects of EO gas sterilization on the poly(L-lactide) (PLLA) microspheres were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), scanning electron microscope (SEM) and size fractionation. The aggregation between the microspheres might be stimulated by high mobility of amorphous regions of PLLA on the microsphere surfaces since both water vapor and gas mixture can reduce glass transition temperature (Tg) of PLLA below the sterilization temperature. During EO gas sterilization, there were no changes in the molecular structure and the molecular weight of PLLA in microspheres, but there were changes in the crystallinity of PLLA in microspheres. In this study, poly(L-lactide)-poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA homopolymers in various ratios to design the microsphere suitable for EO gas sterilization. Aggregation of PLLA microspheres was markedly prevented when more than 4wt% of PLE was blended in the microspheres. This inhibition effect on aggregation may be due to the increased initial crystallinity of the microspheres, which help to maintain the microsphere morphology during EO gas sterilization.

Calorimetry, Differential Scanning↗

PubMed2001

Taxol-loaded block copolymer nanospheres composed of methoxy poly(ethylene glycol) and poly(epsilon-caprolactone) as novel anticancer drug carriers.

We prepared the methoxy poly(ethylene glycol) (MePEG)/poly(epsilon-caprolactone) (PCL) amphiphilic block copolymeric nanospheres containing taxol which has promising anticancer activity. MePEG/PCL block copolymeric nanospheres (MEP50) showed a narrow size distribution and an average diameter of less than 100 nm. When the initial weight ratio of taxol to polymer was 0.5:1.0, we could obtain the nanospheres having a relatively high drug-loading of more than about 20%. The size of the MePEG/PCL nanospheres also increased according to the taxol loading. However, the nanospheres did not exhibit a significant change in the size distribution and also showed a size of less than 100 nm for even that with drug-loading content (DLC) of about 20%. From the 1H NMR analysis, we identified that the MePEG/PCL nanospheres prepared by dialysis procedure have core-shell structure consisting of the hydrophilic outer shell of MePEG and the hydrophobic inner core of PCL. We confirmed the low toxicity of MePEG/PCL nanospheres (MEP70) in the acute toxicity study using male ICR mice. In addition, considering the extremely lipophilic characteristics of taxol, this MePEG/PCL, nanosphere system with high taxol loading content and suspended properties in water could be useful for the delivery of taxol.

Animals↗

PubMed2001

Indomethacin-loaded methoxy poly(ethylene glycol)/ poly(epsilon-caprolactone) diblock copolymeric nanosphere: pharmacokinetic characteristics of indomethacin in the normal Sprague-Dawley rats.

We prepared the drug-loaded polymeric nanospheres composed of the methoxy poly(ethylene glycol) (MePEG) and poly(epsilon-caprolactone) (PCL) that showed a narrow size distribution and average diameter of less than 200 nm. We could obtain the nanosphere having a relatively high drug-loading efficiency of about 42% when the feed weight ratio of indomethacin (IMC) to polymer was 1:1. To investigate the IMC pharmacokinetics in the IMC-loaded MePEG/PCL nanosphere (DMEP70) using the rats as animal model, we analyzed the IMC concentration in plasma with HPLC after i.v. bolus administered at a dose of 10 mg/kg in free IMC (control) and IMC-loaded MePEG/PCL nanosphere (DMEP70) groups via tail vein. Pharmacokinetics parameters (mean +/- s.d.) such as the mean residence time (MRT, h), the steady-state volume of distribution (Vdss, l), the terminal half-time (t 1/2, h) and the plasma clearance (CL, l/h) of IMC in each groups (control vs. DMEP70) were determined; MRT (16.97 +/- 4.83 vs. 28.69 +/- 11.28, p < 0.01); Vdss (14.26 +/- 4.86 vs. 20.37 +/- 12.04, p < 0.05); t 1/2 (15.12 +/- 4.77 vs. 23.1 +/- 8.24, p < 0.01); CL (0.84 +/- 0.27 vs. 0.71 +/- 0.41). From these results, we could concluded that MEP70 has a significant potential for sustained release and the enhancement of circulation time of loaded drug by prolonging terminal half-life, increasing MRT and Vdss of IMC. Therefore, The MePEG/PCL block copolymeric nanosphere system is being considered as promising biodegradable and biocompatible drug carrier vehicles for parentral use and may be useful as sustained release injectable delivery systems for hydrophobic drugs.

Animals↗

PubMed2001

A comparative study of quantitative structure activity relationship methods based on antitumor diarylsulfonylureas.

A series of 28 diarylsulfonylureas with antitumor activity was subjected to a three-dimensional quantitative activity relationship (3D-QSAR) study. Three different QSAR methods, comparative molecular field analysis (CoMFA), hologram QSAR (HQSAR) and comparative molecular similarity indices analysis (CoMSIA), were compared in terms of their potential for predictability. All three QSAR-based models had good predictability and yielded q(2) values 0.74, 0.63 and 0.72, respectively. The CoMFA model provided the highest q(2) and r(2) values, which implied the significance of correlation of steric and electrostatic fields with biological activities. The number of components was 3-4 for all three QSAR methods. The quality of HQSAR or CoMSIA was slightly lower than that of CoNFA in terms of q(2) and r(2) values. HQSAR does not require the generation of a three-dimensional structure of molecules and CoMSIA does not require molecular superposition, therefore they are faster than CoMFA in data processing.

Alkanes↗

PubMed2001

Inactivation of catalase and superoxide dismutase by singlet oxygen derived from photoactivated dye.

Both superoxide dismutase (SOD) and catalase are key enzymes in the antioxidant system of the cells that work to maintain low steady-state concentrations of the reactive oxygen species. When exposed to a singlet oxygen-producing system composed of dye, such as methylene blue or rose bengal, and visible light both SOD and catalase were susceptible to oxidative modification and damage as indicated by the loss of activity, fragmentation and aggregation of peptide as well as by the formation of carbonyl groups. Histidine, a powerful quenching agent for singlet oxygen, and the polyamines, such as spermine and spermidine, were effective at protecting the activity loss mediated by illuminated dye, whereas spin traps were only mildly effective. The structural alterations of modified enzymes were indicated by the increase in susceptibility to proteases, the change in absorption spectra and in fluorescence spectra. The singlet oxygen-mediated damage to SOD and catalase may result in the perturbation of cellular antioxidant defense mechanisms and subsequently lead to a pro-oxidant condition.

Animals↗

PubMed2001

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia.

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.

Animals↗

PubMed2001

N-(3-Acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics.

A series of N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin. which includes the C20 homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 microg kg for 23 and 1.0 microg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency.

Analgesics↗

PubMed2001

Activity monitoring for nitrifying bacteria by fluorescence in situ hybridization and respirometry.

The activities of two families of nitrifying bacteria were measured by applied respirometer and fluorescence in situ hybridization (FISH) for the purpose of monitoring nitrogen removal. Oxygen uptake rates (OUR) for Nitrosomonas and Nitrobacter were separately measured with the dosing of selective inhibitors during respirometric monitoring. The FISH method was applied to analyze microorganism communities. In 5 mg NH4+-N/L solution, the total nitrogen oxygen demand (NOD) was found to be 6,672 mg DO/L-day with ammonia and nitrite oxidation rate of 4,512 and 2,160 mg DO/L-day, respectively. The oxygen consumption by endogenous oxidation was 288 mg DO/L-day and the biological oxygen demand 936 mg DO/L-day. Respirometric measurements were well matched by the FISH result, which described the presence and quantity of each nitrifying bacteria as nitrification proceeded. It was found that when coupled with OUR data, FISH could provide valuable information about the nitrogen removal process in many practical wastewater treatment systems.

Ammonia↗

PubMed2001

Ceramide inhibits cell proliferation through Akt/PKB inactivation and decreases melanin synthesis in Mel-Ab cells.

Ceramide is a bioactive sphingolipid that mediates a variety of cell functions. However, the effects of ceramide on cell growth and the melanogenesis of melanocytes are not known. In the present study, we investigated the actions of cell-permeable ceramide and its possible role in the signaling pathway of a spontaneously immortalized mouse melanocyte cell line, Mel-Ab. Our results show that C2-ceramide inhibits DNA synthesis in Mel-Ab cells and G361 human melanoma cells in a dose-dependent manner. Cell cycle analysis confirmed the inhibition of DNA synthesis by a reduction in the S phase. To investigate the ceramide signaling pathway, we studied whether C2-ceramide is able to influence extracellular signal-regulated kinase (ERK) and/or Akt/protein kinase B (PKB) activation. We demonstrated that phosphorylated Akt/PKB is decreased by C2-ceramide, whereas phosphorylated ERK was only slightly affected. Therefore, the C2-ceramide-induced inactivation of Akt/PKB may be closely related to the reduced cell proliferation of Mel-Ab cells. Furthermore, we assessed the effects of C2-ceramide on the pigmentation of Mel-Ab cells. The results obtained showed that the melanin content of cells was significantly reduced by C2-ceramide at concentrations in the range of 1-10 microM, and that the pigmentation-inhibiting effect of C2-ceramide is much greater than that of kojic acid at 1-100 microM. In addition, we found that the activity of tyrosinase is reduced by C2-ceramide treatment. Our results demonstrate that C2-ceramide reduces the pigmentation of Mel-Ab cells by inhibiting tyrosinase activity.

Animals↗

PubMed2001

Increased erythritol production in fed-batch cultures of Torula sp. by controlling glucose concentration.

The effect of glucose concentration on erythritol production by Torula sp. was investigated. The maximum volumetric productivity of erythritol was obtained at an initial glucose concentration of 300 g l(-1) in batch culture. The volumetric productivity was maximal at a controlled glucose concentration of 225 g l(-1), reducing the lag time of the erythritol production. A fed-batch culture was established with an initial glucose concentration of 300 g l(-1) and with a controlled glucose concentration of 225 g l(-1) in medium containing phytic acid as a phosphate source. In this fed-batch culture, a final erythritol production of 192 g l(-1) was obtained from 400 g l(-1) glucose in 88 h. This corresponded to a volumetric productivity of 2.26 g l(-1) h(-1) and a 48% yield.

Cell Division↗

PubMed2001

Vitamin C prevents radiation-induced endothelium-dependent vasomotor dysfunction and de-endothelialization by inhibiting oxidative damage in the rat.

1. The present study was undertaken to determine whether endothelial function or morphology was altered in aortic rings of rats after irradiation, to investigate the mechanism of radiation effects on the endothelium and to examine the effect of vitamin C treatment against radiation-induced damage of the endothelium. 2. Female Sprague-Dawley rats were randomized into four groups (control, radiation, radiation + vitamin C, radiation + vitamin C + NG-nitro-L-arginine methyl ester (L-NAME); n = 10 for each group and n = 7 for the control group) and were irradiated with 10 Gy of 137Cs as a radiation source. Segments of the thoracic aorta were obtained and isometric tension, levels of 8-hydroxydeoxyguanosine (OH-dG) and immunohistochemical staining were measured. 3. Irradiation significantly impaired the acetylcholine-induced vasodilation of aortic segments, an effect that could be prevented by pretreatment with vitamin C (500 mg/kg per day). This beneficial effect of vitamin C was abolished by the addition of L-NAME (100 microg/kg per day), an inhibitor of nitric oxide (NO) synthesis. Irradiation significantly increased the level of OH-dG in the aorta (1.02 +/- 0.27 vs 2.61 +/- 0.78 OH-dG/105 deoxyguanosine (dG) for control and irradiated tissues, respectively; P < 0.01), an increase that was prevented by vitamin C treatment (1.59 +/- 0.23 OH-dG/105 dG; P < 0.01). Irradiation caused significant de-endothelialization (von Willebrand factor (vWF) staining was 93 +/- 7 vs 100% in irradiated and control tissues, respectively; P < 0.05) and this was prevented by vitamin C treatment (vWF staining 98 +/- 3%; P < 0.05). 4. Radiation caused endothelial damage and impaired NO production through oxidative injury, resulting in a selective impairment of endothelial-dependent vasodilation that could be prevented by vitamin C, partly through anti-oxidant mechanisms.

Acetylcholine↗