Biomedical subjects

X Deng

Publications and source records attributed to X Deng.

At least 91 records · Page 5Linked to original sources

PubMed2000

Effect of 8-bromo-cyclic AMP on neuron specific enolase, heat shock protein, nitric oxide, nitric oxide synthase and nitric oxide synthase mRNA in human retinoblastoma HXO-Rb44 cells and cell differentiation.

OBJECTIVE: To study the effect of 8-bromo-cyclic AMP (8-Br-cAMP) on nitric oxide synthase (NOS) mRNA, NOS and nitric oxide (NO) product, heat shock protein (hsp) 70 and neuron specific enolase (NSE) in human retinoblastoma HXO-Rb44 cells and the effect related to cell differentiation. METHODS: Cultured human retinoblastoma HXO-Rb44 cells were divided into two aliquots. One was cultured with 2 x 10(-5) mol/L of 8-Br-cAMP for 24 hours as the experiment group; the other was treated with no 8-Br-cAMP as the control group. The cell suspensions in concentration of 1 x 10(7)/ml in both groups were dropped onto the nitrocellulose membrane (NCM). The NOS mRNA was detected with the biotin-labeled NOS cDNA probe by RNA dot blot. The NOS activity was detected by protein dot blot. The immunoreactivity (IR) of hsp70 and NSE was detected by protein dot blot. The NO was detected by nitrate reductase method. NCM specimens were analyzed by a TLC scanner for detection of the dot blot signal intensity. RESULTS: The signals of NOS mRNA, NOS activity, hsp70-IR, NSE-IR, and NO content in the experiment group were higher than those in the control group (P < 0.05-0.01). CONCLUSIONS: 8-Br-cAMP could increase NO product and the expression of NOS mRNA, NOS, NSE and hsp70. The results indicate that 8-Br-cAMP could facilitate synthesis of NO in the neuroblastoma HXO-Rb44 cells, which could have tendency toward neuron development, suggesting that the increased hsp70, NO and NOS may involve cell differentiation of the retinoblastoma HXO-Rb44.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

[The effect of progesterone on proliferation and apoptosis in ovarian cancer cell].

OBJECTIVE: To investigate the regulatory effect of progesterone on proliferation and apoptosis in ovarian cancer cell line HO8910 in vitro. METHODS: Ovarian cancer cell line HO8910 originated from human ovarian serous cystadenocarcinoma was cultured in vitro. Two groups were set up: study group (progesterone in different concentrations) and control group without progesterone. Cell proliferation was measured by 3-(4, 5-dimethylthiazol-z-yl)-2,5-dipheny tetrazolium blue (MTT) colorimetric assay. Cell cycle and apoptotic percentage were detected by flow cytometry, morphological changes of apoptotic cells were observed by light and electron microscopy, and apoptotic cells were quantitatively determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). In addition, expression of intracellular bcl-2 protein was analyzed by flow cytometric indirect immunofluorescent technique. RESULTS: Progesterone of 1 x 10(-7)-1 x 10(-5) mol/L inhibited HO8910 cell growth significantly in a dose-dependent manner (P < 0.01). After treatment with progesterone, the enhanced G0/G1 arrest was accompanied with the enhanced apoptotic peak and percentage, as well apoptotic cells were found more than those in control group (P < 0.05). By light and electron microscopy, there were many morphological characteristics of apoptosis including compaction and margination of nuclear chromatin, nuclear fragments, and apoptotic bodies. Analysis on expression of intracellular bcl-2 protein showed that progesterone could down-regulate bcl-2 protein and at concentration of 1 x 10(-5) mol/L it could almost block bcl-2 expression. CONCLUSIONS: It is suggested in the present study that progesterone can inhibit the proliferation of epithelial ovarian cancer cells in vitro and there is an accordant dose-response relationship. Its anticancer effect seems to be due to induction of apoptosis which maybe a result of down-regulation of the anti-apoptotic protein bcl-2.

Apoptosis↗

PubMed2000

[A case-control study on the risk factors of epidemic hemorrhagic fever].

OBJECTIVE: To study the risk factors of epidemic hemorrhagic fever (EHF). METHODS: A 1:1 matched case-control study was conducted to analyse EHF risk factors. RESULTS: One hundred and eighty-five matched pairs were investigated. Five factors were associated with risks of the disease, including rodent activity in house, farm working, travel, annual average income of an individual and ground material of the house, when chi(2) test and logistic regression model were processed respectively. The coefficients of rodent activity in house, farm working, travel, annual average income of an individual and ground material of the house in multivariable Logistic regression model were 1.377, 1.687, 1.630, -1.216 and -0.888, respectively, when P value < 0.05 was observed. CONCLUSIONS: Factors as high average income of individuals, brick or cement used as material of the ground in the house, seemed to be protective factors of EHF, which were important to the control and prevention of EHF.

Adult↗

PubMed2000

[Construction of a novel Bm NPV Bac to Bac system].

A Bi-Shuttle vector Bm-Bacmid was constructed by co-infecting Bm N cells with wild type genomic DNA from BmNPV and Ac-Bacmid DNA. It could not only replicate in E. coli cells as a large plasmid and but also remain infectious when induced into Bm N or Sf9 cells. Recombinant virus rBmHBe was obtained after transposition of a donor plasmid carrying Hepatitis Be antigen gene (HBeAg) into att Tn7, and was demonstrated by Southern blotting. SDS-PAGE analysis showed that HBeAg gene were highly expressed in Bm N cells. By ELISA testing, the highest antigenecity titer of HBeAg protein in cell cultural medium was up to a dilution of 1:32,000. Although HBeAg protein also presented in the Bm N cells the titer was only 1:2000. The HBcAg protein was much fewer than HBeAg (< 1:160) whatever in culture medium and in cells. The results showed that Bm N cells was able to recognize the signal peptide sequence and cut it correctly for HBeAg protein's excreting production.

Animals↗

PubMed2000

[Preoperative superselective intra-internal iliac arterial chemotherapy for invasive bladder cancer and curative analysis].

OBJECTIVE: To study clinical effects of preoperative intra-internal iliac-arterial chemotherapy for invasive bladder cancer. METHODS: 14 cases of invasive bladder cancer underwent superselective intra-internal iliac-arterial chemotherapy before conservative cystectomy. RESULTS: After 2-3 week therapy, reduction of cancer volume (20%-50%), clotted by thrombus in the blood vessels of the cancer or circumferential tissue, and decreased bleeding were found. Pathomorphological features included large patchy necrosis, degeneration, and inflammatory changes of carcinoma tissue. Follow-up ranged from 5 to 42 months (mean 19.6 months). One T3 N1 M0) of the cases (0.7%) relapsed into T1N0M0 and the others did not. CONCLUSIONS: The intra-internal iliac-arterial method, simple, safe, coordinates in pre-operation for invasive bladder cancer, and increases the operative opportunity for preservation of functional bladder.

Aged↗

PubMed2000

[The summarization of clinical experience of difficult tracheal intubation].

OBJECTIVE: To summarize our experiences and lessons of difficult tracheal intubation for clinical anesthesia reference. METHODS: We had done a retrospective analysis of clinical data on difficult tracheal intubation in 2,825 patients undergoing elective plastic surgery with anesthesia. The main causes of difficult tracheal intubation were the limitations of neck extension (n = 1,169), mouth opening (n = 889), both neck extension and mouth opening (n = 698), and micromaxillary deformity (n = 69). By the Cormack's classification, all the patients had the laryngeal exposure of grade II or more. The tracheal intubations were done under neuroleptanalgesia combined with topical spray of local anesthetic in 439 patients, intravenous anesthesia of sedative drugs and nondepolarizing relaxants of subnormal doses in 629 subjects, and total intravenous or inhaled anesthesia in 1,757 cases, respectively. RESULTS: The difficult tracheal intubations were completed using blind nasal intubations in 142 patients, blind oral intubations with direct laryngoscope in 2,377 patients, oral intubations with fiberoptic stylet rigid laryngoscope in 186 patients, and oral or nasal intubations with flexible fiberoptic bronchoscope in 72 patients. The incidence of successful intubation was 99.7%. The common complication of intubation was airway trauma and its incidence was 19.3% in all the patients. Anesthetic techniques could affect significantly the intubation time and the incidences of complications in the patients with difficult intubation. CONCLUSIONS: By the improvement of anesthetic methods and common intubation techniques, the intubation time and the incidence of complications in the patients with difficult intubations were reduced.

Adolescent↗

PubMed2000

Inhibitory effect of fluvastatin on aortic intimal thickening in normocholesterolemic rabbits.

OBJECTIVE: The anti-atherosclerotic effect of fluvastatin at does insufficient to lower serum cholesterol on the catheter-induced intimal thickering and possible mechanism were investigated in abdominal aorta of rabbits. METHODS: Fifty-six rabbits were randomly divided into eight groups (n = 7, each). Fluvastatin was given mixed with food at daily dose of 8 mg/kg starting 5 days before catheterization. Light microscope, immunohistochemistry, transmission electron microscope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC) proliferation and apoptosis, as well as oncogene expression in vascular wall. RESULTS: At day 10 and day 15 after catheter induced denudation intima/media (I/M) thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of alpha-SM-actin-positive cells. In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin. The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expression. CONCLUSION: Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.

Animals↗

PubMed1999

Methamphetamine administration causes overexpression of nNOS in the mouse striatum.

The accumulated evidence suggests that the overproduction of nitric oxide (NO) is involved in methamphetamine (METH)-induced neurotoxicity. Using NADPH-diaphorase histochemistry, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) antibody immunohistochemistry, the possible overexpression of nNOS and iNOS was investigated in the brains of mice treated with METH. The number of positive cells or the density of positive fibers was assessed at 1 h, 24 h and 1 week after METH injections. There were no clear positive iNOS cells and fibers demonstrated in the brains of mice after METH treatment. In contrast, METH caused marked increases in nNOS in the striatum and hippocampus at 1 and 24 h post-treatment. The nNOS expression normalized by 1 week. There were no statistical changes in nNOS expression in the frontal cortex, the cerebellar cortex, nor in the substantia nigra. These results provide further support for the idea that NO is involved in the neurotoxic effects of METH.

Animals↗

PubMed1999

Null mutation of c-fos causes exacerbation of methamphetamine-induced neurotoxicity.

Methamphetamine neurotoxicity has been demonstrated in rodents and nonhuman primates. These neurotoxic effects may be associated with mechanisms involved in oxidative stress and the activation of immediate early genes (IEG). It is not clear, however, whether these IEG responses are involved in a methamphetamine-induced toxic cascade or in protective mechanisms against the deleterious effects of the drug. As a first step toward clarifying this issue further, the present study was thus undertaken to assess the toxic effects of methamphetamine in heterozygous and homozygous c-fos knock-out as well as wild-type mice. Administration of methamphetamine caused significant reduction in [(125)I]RTI-121-labeled dopamine uptake sites, dopamine transporter protein, and tyrosine hydroxylase-like immunohistochemistry in the striata of wild-type mice. These decreases were significantly exacerbated in heterozygous and homozygous c-fos knock-out mice, with the homozygous showing greater loss of striatal dopaminergic markers. Moreover, in comparison with wild-type animals, both genotypes of c-fos knock-out mice showed more DNA fragmentation, measured by the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end-labeled nondopaminergic cells in their cortices and striata. In contrast, wild-type mice treated with methamphetamine demonstrated a greater number of glial fibrillary acidic protein-positive cells than did c-fos knock-out mice. These data suggest that c-fos induction in response to toxic doses of methamphetamine might be involved in protective mechanisms against this drug-induced neurotoxicity.

Animals↗

PubMed1999

A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R.

Because envelope gp120 of various strains of human immunodeficiency virus type 1 (HIV-1) downregulates the expression and function of a variety of chemoattractant receptors through a process of heterologous desensitization, we investigated whether epitopes derived from gp120 could mimic the effect. A synthetic peptide domain, designated F peptide, corresponding to amino acid residues 414-434 in the V4-C4 region of gp120 of the HIV-1 Bru strain, potently reduced monocyte binding and chemotaxis response to macrophage inflammatory protein 1beta (MIP-1beta) and stromal cell-derived factor 1alpha (SDF-1alpha), chemokines that use the receptors CCR5 and CXCR4, respectively. Further study showed that F peptide by itself is an inducer of chemotaxis and calcium mobilization in human monocytes and neutrophils. In cross-desensitization experiments, among the numerous chemoattractants tested, only the bacterial chemotactic peptide fMLF, when used at high concentrations, partially attenuated calcium mobilization induced by F peptide in phagocytes, suggesting that this peptide domain might share a 7-transmembrane, G-protein-coupled receptor with fMLF. By using cells transfected with cDNAs encoding receptors that interact with fMLF, we found that F peptide uses an fMLF receptor variant, FPRL1, as a functional receptor. The activation of monocytes by F peptide resulted in downregulation of the cell surface expression of CCR5 and CXCR4 in a protein kinase C-dependent manner. These results demonstrate that activation of FPRL1 on human moncytes by a peptide domain derived from HIV-1 gp120 could lead to desensitization of cell response to other chemoattractants. This may explain, at least in part, the initial activation of innate immune responses in HIV-1-infected patients followed by immune suppression.

Acquired Immunodeficiency Syndrome↗

PubMed1999

Ceramide induces Bcl2 dephosphorylation via a mechanism involving mitochondrial PP2A.

Phosphorylation of Bcl2 at serine 70 is required for its potent anti-apoptotic function. We have recently shown that Bcl2 phosphorylation is a dynamic process that involves the protein kinase C alpha and protein phosphatase 2A (PP2A) (Ruvolo, P. P., Deng, X., Carr, B. K., and May, W. S. (1998) J. Biol. Chem. 273, 25436-25442; and Deng, X., Ito, T., Carr, B. K., Mumby, M. C., and May, W. S. (1998) J. Biol. Chem. 273, 34157-34163). The potent apoptotic agent ceramide can activate a PP2A, suggesting that one potential component of the ceramide-induced death signal may involve the inactivation of Bcl2. Results indicate that C2-ceramide but not inactive C2-dihydroceramide, was found to specifically activate a mitochondrial PP2A, which rapidly and completely induced Bcl2 dephosphorylation and correlated closely with ceramide-induced cell death. Using a genetic approach, the gain-of-function S70E Bcl2 mutation, which mimics phosphorylation, fails to undergo apoptosis even with the addition of high doses of ceramide (IC50 > 50 microM). In contrast, cells overexpressing exogenous wild-type Bcl2 were sensitive to ceramide at dosages where PP2A is fully active and Bcl2 would be expected to be dephosphorylated (IC50 = 14 microM). These findings indicate that in cells expressing functional Bcl2, the mechanism of death action for ceramide may involve, at least in part, a mitochondrial PP2A that dephosphorylates and inactivates Bcl2.

Animals↗

PubMed1999

T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor.

Human immunodeficiency virus type 1 (HIV-1) envelope protein gp41 mediates viral fusion with human host cells. The peptide segment T20/DP178, located in the C-terminus of the ectodomain of gp41, interacts with the N-terminal leucine zipper-like domain on gp41 to establish the fusogenic conformation of the virus. Synthetic T20/DP178 peptide is highly efficacious in inhibiting HIV-1 infection in vitro by disrupting the transformation of fusogenic status of viral gp41; thus, it has been proposed for clinical trial. We report that synthetic T20/DP178 is a chemoattractant and activator of human peripheral blood phagocytes but not of T lymphocytes. We further demonstrate that T20/DP178 specifically activates a seven-transmembrane, G-protein-coupled phagocyte receptor for N-formylated chemotactic peptides, formyl peptide receptor (FPR). Moreover, synthetic T20/DP178 analogs lacking N-terminal amino acids acted as FPR antagonists. Our results suggest that gp41 peptides regulate phagocyte function via FPR and identify a novel mechanism by which HIV-1 may modulate innate immunity.

Cells, Cultured↗

PubMed1999

Investigation on process parameters involved in preparation of poly-DL-lactide-poly(ethylene glycol) microspheres containing Leptospira Interrogans antigens.

Block copolymer, poly-DL-lactide-poly(ethylene glycol) (PELA) with 11.5% of poly(ethylene glycol) (PEG) content was prepared by bulk ring-opening polymerization using stannous chloride as initiator. PELA microspheres with entrapped Leptospira Interrogans antigens, outer membrane protein (OMP) were elaborated by solvent extraction method based on the formation of multiple w/o/w emulsion, and the resulting microspheres were characterized with respect to particle size, OMP entrapment and morphology characteristics. The purpose of the present study is to perform the optimization of preparative parameters for OMP-loaded PELA micropsheres to control particle size and improve the OMP encapsulation efficiency. Of all the parameters investigated, the polymer concentration of organic phase and the external aqueous phase volume play major roles on particle size, while the organic phase volume, internal aqueous phase volume and the addition of surfactant into the internal aqueous phase display considerable effects on OMP loading efficiency. A small volume of internal aqueous phase and intermediate volumes of organic phase and external aqueous phase were favorable to achieve micropsheres with a size of 1-2 microns and high antigen encapsulation efficiency (70-80%). In vitro OMP release profiles from PELA microspheres consist of a small burst release followed by a gradual release phase. The OMP release rate shows some relations with the porous and water-swollen inner structure of the microspheres matrix. The presence of surfactant in microspheres accelerates OMP release, but the OMP entrapment within microspheres shows limited effects on the release profile.

Antigens, Bacterial↗

PubMed1999

[A DNA probe suitable for the detection of chromosome 21 copy number in human interphase nuclei by fluorescence in situ hybridization].

OBJECTIVE: To prepare DNA probe which can be used to accurately detect chromosome 21 copy number in human interphase nuclei by fluorescence in situ hybridization (FISH). METHODS: A probe was produced by universal primer PCR from YAC clone 881D2 and characterized by FISH to metaphases and interphase nuclei of peripheral lymphocytes from 8 normal individuals and 5 patients suffering from trisomy 21. RESULTS: A DNA probe was produced and its characteristics were :(1) Most of the probes ranged in size from 350bp to 750bp; (2) The hybridization signals of the probes were located near centromere on long arm of human chromosome 21; (3) In 1524 metaphases scored, about 99.95% of hybridization signals were located on chromosome 21; (4) The signals were very bright and recognizable easily in both metaphases and interphases nuclei; (5) The expected copy number of chromosome 21 was detected by FISH with the probe in more than 98.40% of interphase nuclei and 99.60% of metaphases. CONCLUSION: The DNA probe reported here is suitable for the detection of chromosome 21 copy number in interphase nuclei and for the study of segregation of chromosome 21 during mitoses of human lymphocytes in culture.

Cell Nucleus↗

PubMed1999

Biochemical maturation of Spam1 (PH-20) during epididymal transit of mouse sperm involves modifications of N-linked oligosaccharides.

Indirect immunofluorescence of mouse caput and caudal sperm shows distinctly different distributions of Spaml protein, which is associated with structural and functional differences of the molecule. Spam1 is uniformly distributed over the surface of the head of caput sperm while in caudal sperm, light and confocal microscopy demonstrate that it is localized to the anterior and posterior regions. The hyaluronidase activity of Spaml in acrosome-intact caput sperm was significantly lower (4.3-fold; P < 0.0001) than that of caudal sperm. The increase in enzymatic activity in caudal sperm is accompanied by a reduction in the molecular weight (MW): in extracts from caput sperm there was a major band at approximately 74 kDa and a minor band at approximately 67 kDa; while for the cauda there was a major band at approximately 67 kDa and minor bands at approximately 70 and -56 kDa. Additionally, the bands from caput sperm were 4.9 to 7.7-fold less intense than those from caudal sperm. This decreased affinity for the polyclonal anti-Spaml suggests the presence of different surface characteristics of the molecule from the two epididymal regions. Computer analysis of the protein structure from Spam1 cDNA sequence reveals four putative N-linked glycosylation sites, and enzymatic deglycosylation suggests that all sites are functional. After endoglycosidase activity of extracts from caput and caudal sperm, both show a major band with a MW of approximately 56 kDa, the size of the membrane-anchored polypeptide backbone. Based on the difference in size and intensity of the Spaml bands and hyaluronidase activities from caput and caudal sperm, the data suggest that the activation of Spaml during epididymal maturation is regulated by deglycosylation.

Acrosome↗

PubMed1999

Microdissection and microcloning of rye (Secale cereale L.) chromosome 1R.

Chromosome 1R was microdissected and collected from mitotic metaphase spreads of rye (Secale cereale L.) by using glass needles. The isolated chromosomes were amplified in vitro by Sau3A linker adaptor-mediated polymerase chain reaction (PCR). After amplification, the presence of rye-specific DNA was verified by Southern hybridization. The second-round PCR products from five 1R chromosomes were cloned into a plasmid vector to create a chromosome-specific library, which produced approximately 220,000 recombinant clones. Characterization of the microclone library showed that the 172 clones evaluated ranged in size from 300-1800 bp with an average size of 950 bp, of which approximately 42% were medium/high copy and 58% were low/unique copy clones. Chromosome in situ hybridization confirmed that the PCR products from microdissected chromosomes originated from chromosome 1R, indicating that many chromosome 1R-specific sequences were present in the library.

Base Sequence↗

PubMed1999

Dexamethasone ameliorates oxidative DNA damage induced by benzene and LPS in mouse bone marrow.

Mice were grouped to receive vehicle, dexamethasone (DEX), lipopolysaccharide (LPS), benzene (BZ, 200 mg/kg) and combinations: LPS + DEX, BZ + DEX, LPS + BZ, LPS + DEX + BZ. The DNA damage in bone marrow cells from BZ group was enhanced 2.8-fold measured by nuclear 8-hydroxy-2 '-deoxyguanosine (8-oxodG) and 1.4-fold measured by Comet score (index of DNA breaks) (p < 0.05). In the BZ + DEX group, 8-oxodG level and the Comet score were lowered to 65% and 76% respectively of that in the BZ group (p < 0.05). The BZ + LPS caused a 3.9-fold increase in 8-oxodG and a 1.6-fold increase in the Comet score (p < 0.05). The LPS + DEX + BZ lowered 8-oxodG level and the Comet score to 50% and 78% of the values in the LPS + BZ group, respectively (p < 0.05). Nitrate/nitrite levels in serum were higher after BZ + LPS treatment than after all other treatments. Both 8-oxodG level and the Comet scores were correlated to the serum nitrate/nitrite level across all the treatments (r = 0.55, p < 0.01 and r = 0.69, p < 0.01, respectively). In bone marrow cells the 8-oxodG correlated with the Comet scores (r = 0.80, p < 0.01). We conclude that DEX administration can reduce the DNA damage from BZ treatment and from the combination of BZ and LPS. The correlation of DNA damage with nitrate/nitrite indicates the possible involvement of reactive nitrogen species (RNS) in the interaction between BZ and the inflammatory reaction stimulated by LPS. The 8-oxodG determination is more sensitive than strand break analysis by the Comet assay in bone marrow in vivo in mice for measuring the BZ-induced DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1999

Potential mechanisms responsible for zymosan-associated endothelial injury in rats.

OBJECTIVE: To assess alterations in endothelial barrier integrity and potential factors involved in zymosan-associated endothelial injury. DESIGN: Experimental study. SETTING: University hospital, Sweden. ANIMALS: 42 adult male Sprague-Dawley rats. INTERVENTIONS: One hour before an intraperitoneal injection of paraffin or zymosan (0.25 mg/g body weight), 1.0 ml of a solution of saline, N-acetyl-L-cysteine, dimethyl sulphoxide, indomethacin, verapamil, or allopurinol was given intravenously. MAIN OUTCOME MEASURES: Measurement of tissue water content, tissue intravascular plasma volume, interstitial fluid volume, and extravascular 125I-labelled human serum albumin distribution as well as plasma concentrations of albumin, alpha1-macroglobulin, alpha2-antiplasmin, and antithrombin III, 24 hours after the intraperitoneal injection. RESULTS: Endothelial permeability significantly increased in abdominal organs and the gastrointestinal tract, and plasma antiplasmin concentrations decreased. Pretreatment with N-acetyl-L-cysteine, dimethyl sulphoxide, or indomethacin protected against zymosan-induced endothelial barrier injury and the decline in protease inhibitors in plasma to varying degrees, while pretreatment with verapamil or allopurinol had a limited effect. CONCLUSION: Oxygen free radicals, prostaglandin, and proteases may have roles in the pathogenesis of zymosan-induced endothelial barrier injuries, implying that several mediators probably are interacting.

Animals↗