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Biomedical subjects

F Wu

Publications and source records attributed to F Wu.

At least 19 recordsLinked to original sources
PubMed2003

Photodegradation of 17alpha-ethynylestradiol in aqueous solution exposed to a high-pressure mercury lamp (250 W).

The photodegradation of 17alpha-ethynylestradiol (EE(2)) induced by high-pressure mercury lamp (lambda> or =313, 250 W) in aqueous solution of EE(2) was investigated initially. The affecting factors on the photodegradation were studied and described in details, such as EE(2) initial concentration, Fe(3+), algae, exposure time, and so on. The concentration of EE(2) in distilled water was mainly determined using fluorescence spectrophotometer. The photodegradation of EE(2) in aqueous solution exposed to high-pressure mercury lamp was evident and could be accelerated by Fe(3+) or algae (e.g. Anabaena cylindrica) in general. With the algae concentration increasing, photodegradation rate increased. In this paper, the mechanism of photocatalytic degradation of EE(2) by Fe(3+) or algae is discussed primarily.

Anabaena↗
PubMed2002

p107 Expression in colorectal tumours rises during carcinogenesis and falls during invasion.

p107 Links to cyclin A/CDK2 (cyclin-dependent kinase 2) and cyclin E/CDK2 that are important cell cycle regulators. However, p107 expression remains unclear in almost all kinds of human solid tumours. To clarify the expression of p107 in colorectal tumours, 22 normal mucosae, 9 hyperplastic polyps, 60 adenomas, 198 primary carcinomas, 21 lymph-nodal metastases, and 10 hepatic metastases were immunohistochemically stained for p107, cyclin A, cyclin E, CDK2 and Ki67. Results were measured using labelling indices (LIs). p107 LIs surpassed the highest value in normal tissues in six of nine hyperplastic polyps, 54 of 60 adenomas, 144 of 198 primary cancers, 13 of 21 nodal foci and three of 10 hepatic foci. p107 LIs also apparently rose from normal through hyperplasia and adenoma to early carcinoma. However, they declined in liver-metastatic foci, and in primary cancers showing large size, mucinous type, venous invasion, lymphatic invasion, poorly differentiated type, deep invasion, lymph-nodal metastasis, hepatic metastasis or advanced stage. Low p107 LIs were also linked to a poor survival, particularly in stage-III patients. As the p107 LI gradually rose, the CDK2 (in primary cancers only), cyclin A, cyclin E and Ki67 LIs were elevated concurrently-in both adenomas and primary cancers. Thus, in colorectal tumours, p107 expression rises abnormally and gradually during carcinogenesis and then falls during invasion, and thereby probably perturbs the cell-cycle control and promotes carcinogenesis and invasion. Clinically, reduced p107 may indicate a poorer prognosis.

Adult↗
PubMed2001

Isolation and partial characterization of dissolved copper-complexing ligands in streamwaters.

We have separated two groups of copper-complexing ligands (the weak and strong ligands) from streamwaters in the Lake Biwa watershed by modified immobilized metal ion affinity chromatography (IMAC). The weak ligands were about 0.54-1.21% of the total dissolved organic matter (DOM), as determined by UV absorbance, and the strong ligands were about 0.06-0.21%. The results show that the stronger ligands were retained longer on the IMAC column, eluted later, and were accompanied by shorter wavelength UV absorbers, fluorescence maxima patterns with shorter wavelength excitation, and relatively "fresher" organic matter. The weak ligands with logK'(CuL) values of 6.6-7.7 had predominant humic-like fluorescence and may have been considerably degraded, while stronger ligands with logK'(CuL) values of 8.9-9.3 had only protein-like fluorescence and were relatively newly produced, labile material, as indicated from their amino acid composition. The protein-like fluorescence was mainly due to aromatic tryptophan probably bound to proteins or peptides. The results presented here have significant implications regarding the possible sources and biogeochemical role of organic ligands in aquatic environments.

Amino Acids↗
PubMed2001

Interleukin-2-induced small unilamellar vesicle coalescence.

Recombinant human interleukin-2 (rhIL-2) was incorporated in liposomes for potential therapeutic applications using a novel process. In this process, rhIL-2 caused the formation of large, unique multilamellar vesicles (MLVs) from small unilamellar vesicles (SUVs) of dimyristoylphosphatidylcholine (DMPC). Vesicle coalescence occurred most rapidly at 19 degrees C, between the pre- and main phase transition temperatures of DMPC, and showed a dependence upon pH (pH <5.5), ionic strength (>50 mM) and the initial size of the unilamellar vesicles (<or=25 nm). Intermediates (partially coalesced vesicles) within the forming multilamellar structures were identified by freeze-fracture electron microscopy and their presence was corroborated by differential scanning calorimetry. Several distinct steps were identified in the coalescence process. In the initial step, rhIL-2 rapidly bound to the DMPC SUVs. This was followed by a pH-dependent conformational change in the protein, as evidenced by an increase in tryptophan fluorescence intensity. The SUVs then aggregated in large clusters that eventually annealed to form closed MLVs. In this process over 90% of the rhIL-2 was bound to and incorporated within the multilamellar structures.

Calorimetry, Differential Scanning↗
PubMed2001

Effects of all-trans-retinoic acid and arsenic trioxide on the hemostatic disturbance associated with acute promyelocytic leukemia.

To study the in vivo effect of all-trans-retinoic acid (ATRA) and arsenic trioxide (As(2)O(3)) on the expression of tissue factor (TF) and the other hemostatic disturbance, a series of parameters were measured either in bone marrow blasts or plasma from acute promyelocytic leukemia (APL) patients. The plasma parameters were measured by ELISA or chromogenic studies. The TF transcription was assessed using reverse transcription-polymerase chain reaction (RT-PCR) technique. The results indicated that the blast cell procoagulant activity (PCA), TF antigen of APL cell lysate, as well as the transcription of APL TF mRNA elevated at diagnosis, were reduced after ATRA or As(2)O(3) therapy. The plasma level of P-selectin, TF, thrombin-antithrombin complex (TAT), soluble fibrinmonomer complex, thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), plasmin-antiplasmin complex, tissue plasminogen activator (t-PA) activity, urokinase plasminogen activator (u-PA) and its receptor (u-PAR), and D-dimer (D-D) significantly increased. Fibrinogen (Fg), antigen level of protein C (PC), plasminogen (PLG) activity, alpha(2)-plasminogen inhibitor activity (alpha(2)-PI), and plasminogen activator inhibitor (PAI) activity were decreased at diagnosis. The protein C activity (PC:A) and protein S (PS) remained unchanged. All the parameters were restored to normal ranges after complete remission (CR) except elevation of TF and TAT in both groups, as well as PC:A, PS, and t-PA in the ATRA group. In conclusion, there existed activation of platelets and consumption of anticoagulants as well as activation of coagulation and fibrinolytic system before treatment. Both ATRA and As(2)O(3) therapy downregulated the expression of TF mRNA, decreased the PCA and TF level in APL cells, significantly inhibited coagulation activation, corrected secondary hyperfibrinolysis and the other hemostatic abnormalities, and thus greatly improved the bleeding symptom in early stage of the treatment.

Adolescent↗
PubMed2001

Deletion of the helical motif in the intestinal fatty acid-binding protein reduces its interactions with membrane monolayers: Brewster angle microscopy, IR reflection-absorption spectroscopy, and surface pressure studies.

Intestinal fatty acid binding protein (IFABP) appears to interact directly with membranes during fatty acid transfer [Hsu, K. T., and Storch, J. (1996) J. Biol. Chem. 271, 13317-13323]. The largely alpha-helical "portal" domain of IFABP was critical for these protein--membrane interactions. In the present studies, the binding of IFABP and a helixless variant of IFABP (IFABP-HL) to acidic monolayers of 1,2-dimyristoylphosphatidic acid (DMPA) has been monitored by surface pressure measurements, Brewster angle microscopy (BAM), and infrared reflection-absorption spectroscopy (IRRAS). Protein adsorption to DMPA exhibited a two phase kinetic process consisting of an initial slow phase, arising from protein binding to the monolayer and/or direct interfacial adsorption, and a more rapid phase that parallels formation of lipid-containing domains. IFABP exhibited more rapid changes in both phases than IFABP-HL. The second phase was absent when IFABP interacted with zwitterionic monolayers of 1,2-dipalmitoylphosphatidylcholine, revealing the important role of electrostatics at this stage. BAM images of DMPA monolayers with either protein revealed the formation of domains leading eventually to rigid films. Domains of DMPA/IFABP-HL formed more slowly and were less rigid than with the wild-type protein. Overall, the IRRAS studies revealed a protein-induced conformational ordering of the lipid acyl chains with a substantially stronger ordering effect induced by IFABP. The physical measurements thus suggested differing degrees of direct interaction between the proteins and DMPA monolayers with the IFABP/DMPA interaction being somewhat stronger. These data provide a molecular structure rationale for previous kinetic measurements indicating that the helical domain is essential for a collision-based mechanism of fatty acid transfer to phospholipid membranes [Corsico, B., Cistola, D. P., Frieden, C. and Storch, J. (1998) Proc. Natl. Acad. Sci. U.S.A. 95, 12174-12178].

Amino Acid Sequence↗
PubMed2001

Structural determinants of the substrate and stereochemical specificity of phosphotriesterase.

Bacterial phosphotriesterase (PTE) catalyzes the hydrolysis of a wide variety of organophosphate nerve agents and insecticides. Previous kinetic studies with a series of enantiomeric organophosphate triesters have shown that the wild type PTE generally prefers the S(P)-enantiomer over the corresponding R(P)-enantiomers by factors ranging from 1 to 90. The three-dimensional crystal structure of PTE with a bound substrate analogue has led to the identification of three hydrophobic binding pockets. To delineate the factors that govern the reactivity and stereoselectivity of PTE, the dimensions of these three subsites have been systematically altered by site-directed mutagenesis of Cys-59, Gly-60, Ser-61, Ile-106, Trp-131, Phe-132, His-254, His-257, Leu-271, Leu-303, Phe-306, Ser-308, Tyr-309, and Met-317. These studies have shown that substitution of Gly-60 with an alanine within the small subsite dramatically decreased k(cat) and k(cat)/K(a) for the R(P)-enantiomers, but had little influence on the kinetic constants for the S(P)-enantiomers of the chiral substrates. As a result, the chiral preference for the S(P)-enantiomers was greatly enhanced. For example, the value of k(cat)/K(a) with the mutant G60A for the S(P)-enantiomer of methyl phenyl p-nitrophenyl phosphate was 13000-fold greater than that for the corresponding R(P)-enantiomer. The mutation of I106, F132, or S308 to an alanine residue, which enlarges the small or leaving group subsites, caused a significant reduction in the enantiomeric preference for the S(P)-enantiomers, due to selective increases in the reaction rates for the R(P)-enantiomers. Enlargement of the large subsite by the construction of an H254A, H257A, L271A, or M317A mutant had a relatively small effect on k(cat)/K(a) for either the R(P)- or S(P)-enantiomers and thus had little effect on the overall stereoselectivity. These studies demonstrate that by modifying specific residues located within the active site of PTE, it is possible to dramatically alter the stereoselectivity and overall reactivity of the native enzyme toward chiral substrates.

Amino Acid Substitution↗
PubMed2001

Enhancement, relaxation, and reversal of the stereoselectivity for phosphotriesterase by rational evolution of active site residues.

The factors that govern the substrate reactivity and stereoselectivity of phosphotriesterase (PTE) toward organophosphotriesters containing various combinations of methyl, ethyl, isopropyl, and phenyl substituents at the phosphorus center were determined by systematic alterations in the dimensions of the active site. The wild type PTE prefers the S(P)-enantiomers over the corresponding R(P)-enantiomers by factors ranging from 10 to 90. Enlargement of the small subsite of PTE with the substitution of glycine and alanine residues for Ile-106, Phe-132, and/or Ser-308 resulted in significant improvements in k(cat)/K(a) for the R(P)-enantiomers of up to 2700-fold but had little effect on k(cat)/K(a) for the corresponding S(P)-enantiomers. The kinetic preferences for the S(P)-enantiomers were thus relaxed without sacrificing the inherent catalytic activity of the wild type enzyme. A reduction in the size of the large subsite with the mutant H257Y resulted in a reduction in k(cat)/K(a) for the S(P)-enantiomers, while the values of k(cat)/K(a) for the R(P)-enantiomers were essentially unchanged. The initial stereoselectivity observed with the wild type enzyme toward the chiral substrate library was significantly reduced with the H257Y mutant. Simultaneous alternations in the sizes of the large and small subsites resulted in the complete reversal of the chiral specificity. With this series of mutants, the R(P)-enantiomers were preferred as substrates over the corresponding S(P)-enantiomers by up to 500-fold. These results have demonstrated that the stereochemical determinants for substrate hydrolysis by PTE can be systematically altered through a rational reconstruction of the dimensions of the active site.

Amino Acid Substitution↗
PubMed2001

YY1 as a regulator of replication-dependent hamster histone H3.2 promoter and an interactive partner of AP-2.

In analyzing cis-regulatory elements important for cell cycle control of the replication-dependent hamster histone H3.2 gene, we discovered a binding site for the transcription factor YY1 embedded within GC-rich sequences between the two tandem CCAAT repeats proximal to the TATA element. Base mutations that specifically eliminated YY1 binding resulted in suppression of the S phase induction of the H3.2 promoter. In addition, we discovered that YY1 is an interactive partner of AP-2, which also binds the H3.2 promoter and regulates its cell cycle-dependent expression. The critical domains for YY1 and AP-2A interaction are mapped, revealing that the N-terminal portion of YY1 (amino acids 1-300) and the DNA-binding/dimerization region of AP-2A are required. Our results suggest that YY1, acting as a transcription factor binding to its site on the promoter, or through protein-protein interaction with AP-2, may be part of a regulatory network including key cell cycle regulators such as c-Myc and Rb in controlling growth- and differentiation-regulated gene expression.

Animals↗
PubMed2001

Rapid bidirectional modulation of mRNA expression and export accompany long-term facilitation and depression of Aplysia synapses.

Serotonin (5-HT) and the neuropeptide Phe-Met-Arg-Phe-amide (FMRFa) modulate synaptic efficacy of sensory neurons (SNs) of Aplysia in opposite directions and for long duration. Both long-term responses require changes in mRNA and protein synthesis. The SN-specific neuropeptide, sensorin A, is a gene product that appears to be increased by 5-HT and decreased by FMRFa. We examined whether changes in sensorin A mRNA levels in the cell body and neurites of SNs accompany long-term facilitation and depression. Both 5-HT and FMRFa evoked rapid changes in sensorin A mRNA levels in the SN cell bodies: an increase with 5-HT and a decrease with FMRFa. Parallel changes in sensorin A mRNA levels in SN neurites were detected 2 h and 4 h later. These rapid changes in mRNA expression and net export required the presence of the appropriate target motor cell L7. The neuromodulators failed to produce changes in mRNA expression or export when SNs were cultured alone or with the inappropriate target cell L11. The changes in mRNA expression were transient because mRNA levels returned to control values 24 h after treatment, while synaptic efficacy remained altered by the respective treatments. These results indicate that two neuromodulators produce distinct, but transient, target-dependent effects on expression and export of a cell-specific mRNA that correlate with changes in synaptic plasticity.

Animals↗
PubMed2001

Evaluation of pyridoindoles, pyridylindoles and pyridylpyridoindoles as matrices for ultraviolet matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

In an effort to gain an understanding of the processes governing ultraviolet matrix-assisted laser desorption/ionization (UV-MALDI), direct comparison was made of the mass spectra of proteins, carbohydrates and synthetic polymers (polyethylene glycol, polyester and polyamide) by using pyridylindoles, pyridoindoles and pyridylpyridoindoles as UV (337 nm)-MALDI-TOFMS matrices in positive and negative ion mode. In order to study the combined effect of the indole N-H and the pyridine nitrogen of the MALDI matrix on the desorption/ionization process in MALDI, compounds were selected that include either or both of these functions in their structure. Within the compounds studied only those that possess simultaneously both functions in a 1,4-relation behave as very good matrices for proteins. These compounds also work as matrices for some carbohydrates and synthetic polymers used as analytes in the present study. Some of the compounds were also found to be useful for the post-source decay (PSD) analysis of cyclodextrins in positive and negative ion mode. In several cases we also examined the matrix behavior of the corresponding N-methylindole derivatives.

Carbohydrates↗
PubMed2001

Regeneration of N, P and Si near the sediment/water interface of lakes from Southwestern China Plateau.

Lake water, pore water, and sediments were sampled in both polluted and unpolluted lakes from Southwestern (SW) China Plateau. The results show that although the mechanisms of nutrient regeneration were similar in the polluted and unpolluted lakes, the processes, however, were much stronger in the polluted lakes. Nitrogen regeneration was mainly of organic process. Phosphorus regeneration was essentially controlled by iron redox cycling near sediment/water interface. Nutrient upward fluxes were in the order SiO2 > NH4+ > PO4(3-). This study has significance for further investigating the response of nutrient biogeochemistry to the increasing nutrient levels in aquatic environments.

China↗
PubMed2001

Pathological changes in human malignant carcinoma treated with high-intensity focused ultrasound.

The purpose of this study was to investigate the pathologic changes of extracorporeal ablation of human malignant tumors with high-intensity focused ultrasound (HIFU). HIFU treatment was performed in the 164 patients with liver cancer, breast cancer, malignant bone tumor, soft tissue sarcoma and other malignant tumors at focal peak intensities from 5000 W x cm(-2) to 20,000 W x cm(-2), with operating frequencies of 0.8 to 3.2 MHz. To explore the pathologic impact of extracorporeal HIFU, 30 patients with malignant carcinoma underwent surgical removal after HIFU treatment. Pathologic findings showed that the treated tissues demonstrated homogeneous coagulative necrosis with an irreversible tumor cell death and severe damage to tumor blood vessels at the level of microsvasculature within the HIFU-targeted region. Thermolesions to intervening tissue were never observed. The treated region had a sharp border comprising only several cell layers between the treated and untreated areas. The repair of lesions had the processes of necrotic tissue absorption and granulation tissue replacement. It is concluded that extracorporeal treatment of human solid malignancies with HIFU could be safe, effective and feasible. As a noninvasive therapy, HIFU would be used clinically to treat patients with solid malignancies.

Bone Neoplasms↗
PubMed2001

Analysis of 76Br-BrdU in DNA of brain tumors after a PET study does not support its use as a proliferation marker.

76Br-bromodeoxyuridine has previously been suggested as a PET tracer to characterize proliferation potential. However, in animal studies a large fraction of the tissue radioactivity is due to 76Br-bromide, which remains extracellular for extensive periods and contributes significantly to the level of radioactivity. The present project aimed at investigating whether in human brain tumors, sufficient amounts of 76Br-bromodeoxyuridine would be incorporated into DNA, to motivate further attempts with this tracer. Eight patients with brain tumors: 3 meningiomas, 2 astrocytoma grade IV, 1 astrocytoma oligodendroglioma grade II-IV and 2 metastases, were examined with PET and 76Br-BrdU on three occasions: immediately after injection of the tracer, at 4-6, and at 18-20 hours after administration. After the first PET study, diuresis was introduced and maintained for about 12 hours. About 20 hours after tracer administration, 200 mg/m(2) bromodeoxyuridine was administered to 7 patients median 5.8 (range 1-22) hours prior to operation allowing the immunohistochemical analysis of the proliferation potential. During the operation, tumor samples were taken and radioactivity in DNA extracted and measured. The uptake of radioactivity was higher in the tumors than in brain parenchyma. However, in the operative samples only 1-27% (average: 9%) of the radioactivity was found in the DNA fraction. The plasma radioactivity remained high throughout the study with only minimal signs of elimination by the diuresis. 76Br-BrdU is extensively metabolized to 76Br-bromide, and only a minor fraction of the radioactivity is found in the DNA fraction, making it unlikely that this tracer can be used for assessment of proliferation potential.

Aged↗
PubMed2001

Analysis of intratumoral heterogeneity of chromosome 3p deletions and genetic evidence of polyclonal origin of cervical squamous carcinoma.

Investigation on intratumoral genetic heterogeneity provides an important insight into the roles of genetic alterations in human carcinogenesis and clues to clonal origin of tumors. Intratumoral heterogeneity of genetic changes of cervical cancer has not been described so far. In this study, we analyzed the intratumoral heterogeneity of chromosome 3p deletions and X-chromosome inactivation patterns in multiple microdissected samples from each individual cervical cancer, attempting to understand the roles of 3p deletions in development of cervical cancer and its clonal origin. Totally, 120 normal and lesional samples from 14 cases of fresh cervicalcancers were analyzed. Frequency and patterns of allelic losses of 3p were assessed by polymerase chain reaction (PCR) amplification of 12 microsatellite markers flanking the frequently deleted regions of 3p, followed by Genescan analysis in an ABI 377 DNA sequencer. Loss of heterozygosity was recorded as heterogeneous pattern (LOH present in parts of samples or LOH involving different alleles among different samples) and homogeneous pattern (LOH involving identical alleles in all samples from the tumor). Allelic loss affecting at least one marker was detected in 8 of 14 cases (57%). Allelic losses, both homogeneous and heterogeneous, were frequently detected at FHIT gene region (D3S1300, 40% and 60%; D3S4103, 27.3% and 54.6%), 3p21.3-21.2 (D3S1478, 27.3% and 45.5%), and 3p24.2-22 (D3S1283, 30% and 50%). Seven of eight LOH-positive tumors exhibited homogeneous allelic loss involving at least one of these three 3p loci. Allelic losses were present in the CIN lesions synchronous with invasive lesions positive for LOH. Our findings suggest essential roles of genes on these 3p loci, particularly the FHIT gene in participating in clonal selection and early development of cervical cancer. Most interestingly, with the combination of LOH analysis and X-chromosome inactivation analysis, we provided the first clear genetic evidence of polyclonal origin of cervical invasive cancer in two of eight cases. This finding strongly suggests the importance of field defect (possible human papilloma virus) in cervical carcinogenesis.

Adult↗
PubMed2001

Studies on the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide in the treatment of relapsed acute promyelocytic leukemia: a comparison with conventional dosage.

Twenty cases of patients with relapsed acute promyelocytic leukemia (APL) were entered into this study for evaluating the clinical efficacy and pharmacokinetics of low-dose arsenic trioxide (As2O3). As2O3 was given at a daily dose of 0.08 mg/kg intravenously for 28 days. Pharmacokinetic study was carried out in eight patients. 16/20 (80%) patients achieved CR. The occurrence of some toxic events including gastrointestinal disturbance, facial edema and cardiac toxicity seemed reduced in the low-dose group than those in the standard-dose group. Differentiation changes were observed in peripheral blood, as well as in bone marrow (BM). Pharmacokinetic study showed that the plasma concentration increased soon after administration of As2O3 with the peak values of 1.535-3.424 micromol/l. After infusion, the plasma concentration was around 0.1-0.5 micromol/l. The arsenic concentration of the plasma of BM aspirates 24 h after administration in five patients was close to the level needed for differentiation-inducing effect. The estimated 2-year OS and RFS were 61.55+/-15.79% and 49.11+/-15.09% respectively, with no difference as compared with those in patients treated with conventional dose (P = 0.2865 and 0.7146, respectively). In conclusion, we demonstrated that low-dose As2O3 had the same effect as the conventional dosage and the mechanism of low-dose arsenic seemed to primarily induce differentiation of APL cells.

Adolescent↗
PubMed2001

Nitric oxide attenuates but superoxide enhances iNOS expression in endotoxin- and IFNgamma-stimulated skeletal muscle endothelial cells.

OBJECTIVE: Endothelial cells (ECs) in septic skeletal muscle may be exposed to large amounts of NO and superoxide generated by the skeletal muscle cells. We tested the hypothesis that inducible nitric oxide synthase (iNOS) induction in ECs (i.e., one of the steps in the septic process) is modulated by extravascularly generated nitric oxide (NO) and superoxide. METHODS: To model sepsis in vitro, monolayers of microvascular ECs derived from rat skeletal muscle were incubated with a mixture of lipopolysaccharide (LPS) (25 ng/mL) and interferongamma (IFNgamma) (100 U/mL) for up to 24 hours. Next, a long-term release NO donor (DETA NONOate), a superoxide-generating mixture (xanthine oxidase/xanthine; XO/X), or DETA + XO/X were added to the LPS + IFNgamma mixture. The iNOS protein and activity, as well as intracellular oxidative stress, were measured at intervals up to 24 hours, whereas the activation of AP-1, IRF-1, and NFkappaB transcription factors was determined at 2 and 24 hours. RESULTS: LPS + IFNgamma caused time-dependent increases in iNOS protein and activity. Increasing concentrations of DETA (up to 500 microM) decreased, whereas XO/X (10 mU per mL/0.1 mM, respectively) markedly enhanced, iNOS expression and activity. DETA attenuated the enhancement by XO/X. Although intracellular oxidative stress was not altered by LPS + IFNgamma, modulations of iNOS expression by DETA, XO/X, and DETA + XO/X correlated with changes in oxidative stress. Among the three transcription factors, only IRF-1 and NFkappaB seemed to be involved in iNOS induction and its modulation by DETA and XO/X. CONCLUSIONS: LPS + IFNgamma can induce iNOS expression in microvascular ECs from rat skeletal muscle, whereas NO and superoxide modulate this expression. On the basis of these observations we suggest that NO and superoxide from the extravascular tissue may play a key role in the inflammatory response of septic ECs.

Animals↗