Quantitative evaluation of the impact of indoor relative humidity on deposition of aerosols generated during tooth grinding in a real-world clinical setting.

OBJECTIVES: Exposure to aerosol particles generated from tooth grinding has a negative impact on the health of dental personnel. The aim of this study was to quantitatively analyze the impact of indoor relative humidity (IRH) on the deposition of these suspended particles in a well-controlled dental environment. MATERIALS AND METHODS: In this study, a humidity control system was employed to effectively regulate and maintain indoor relative humidity (IRH). A novel computer-assisted numerical control system was developed to pre-treat the molar specimens, and accurately simulate clinical tooth grinding procedures. Each procedure was performed in triplicate, with an online real-time particle counter (ORPC; TR-8301, TongrenCo.) measuring aerosol production. All testing devices were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Kruskal-Wallis/ Dunn's post hoc test with Bonferroni correction, p < 0.05). RESULTS: The findings showed that with increasing IRH, the maximum peak concentration of aerosol particles decreased by 397% from 6.51 × 107 particles/m3 at 30% to 1.64 × 107 particles/m3 at 80%. The Kruskal-Wallis test results indicated a statistically significant effect of IRH on the aerosol increment (p < 0.05). CONCLUSIONS: Increasing the IRH level can effectively promote the deposition of aerosol particles, with a return to baseline within 15 min after reaching 60% or above. CLINICAL RELEVANCE: Our study suggested that maintaining IRH above 70% during the cleaning process, allowing natural recovery to ambient humidity levels within 15 min after cleaning, and taking basic precautions, may lead to an adequate reduction in the possible health risks of aerosol contamination.

Quantitative assessment of aerosol contamination generated during tooth grinding with a speed-increasing handpiece.

OBJECTIVES: Tooth grinding produces a significant amount of aerosol particles. The aim of this study was to quantitatively assess particle contamination produced from tooth grinding with a speed-increasing handpiece across a real-world clinical setting. METHODS: All molar crowns were pretreated into cylinders with a uniform size. A novel computer-assisted numerical control system was used to parametrically study the bur speed: from 20,000 (20 K) to 200 K rpm at 20 K rpm intervals. 5-minute tooth grinding was performed in triplicate at each speed setting. Three online real-time particle counters (ORPC; TR-8301, TongrenCo.) were placed at 3 positions (0.5, 1, and 1.5 m) to evaluate particle production. All experimental instruments were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Scheirer-Ray-Hare and Kruskal-Wallis/ Dunn-Bonferroni tests, p < 0.05). RESULTS: The concentration level of aerosol particles production during the grinding experiment was elevated above the control group for all conditions, and increased with bur speed at any location (the maximum peak, reaching 5.59 × 107 particles/m3, at 200 K and 1 m), with differences between conditions. The effect of speed on the increment of particles across different channels compared to the control group was statistically significant among locations (p < 0.001). CONCLUSIONS: Statistically significant particle contamination was produced using a speed-increasing handpiece, but the contamination level for each experimental condition was reduced to baseline within 30 min, and most particles with a diameter greater than 1üm produced at low speeds (80 K or lower) tended to settle within 1 m. CLINICAL RELEVANCE: Our study suggested that the use of a speed-increasing handpiece below 80 K and 30 min of fallow time may lead to an adequate reduction in the health effects of particle contamination.

Targeted elimination of intracellular reactive oxygen species using nanoparticle-like chitosan- superoxide dismutase conjugate for treatment of monoiodoacetate-induced osteoarthritis.

In our previous work, cationic functionalized chitosan was chemically conjugated with superoxide dismutase (SOD) to yield a unique nanoparticle-like conjugate O-HTCC-SOD that has demonstrated superior potential in treating reactive oxygen species (ROS)-related disorders to SOD. Considering contribution of ROS to pathogenesis of osteoarthritis, O-HTCC-SOD was firstly measured for effect on rat chondrocytes exposure to monoiodoacetate (MIA). O-HTCC-SOD was nontoxic to chondrocytes and had more long-acting and intracellular protection effects on chondrocytes against MIA-induced oxidative damage due to its superior elimination of intracellular ROS to SOD. Pharmacokinetic analysis demonstrated that O-HTCC-conjugated SOD significantly prolonged half-life and residence in rat joint cavity, and improved bioavailability compared with unmodified SOD. Intra-articular injection of O-HTCC-SOD significantly attenuated mechanical allodynia in MIA-induced osteoarthritis rats, dramatically suppressed gross morphological and histological lesions of articular cartilage, and greatly enhanced in vivo antioxidant capacity and anti-inflammatory effect. But native SOD had no obvious therapeutic effects. Consequently, the nanoparticle-like conjugate O-HTCC-SOD of the excellent efficacy resulted from its targeted intracellular ROS clearance capability and improved pharmacokinetic profiles, opening up a novel avenue for disease-modifying osteoarthritis drugs.

Uncovering the detailed mode of cleavage of heparinase I toward structurally defined heparin oligosaccharides.

For a more insightful investigation into the specificity of bacterial heparinase I, a series of structurally well-defined heparin oligosaccharides was synthesized using a highly efficient chemoenzymatic strategy. Apart from the primary cleavage site, five glycosidic linkages of oligosaccharides with varying modifications to obtain secondary cleavage sites were degraded by a high concentration of heparinase I. The reactivity of linkages toward heparinase I was not entirely dependent on the 2-O-sulfated iduronic acid being cleaved or the neighboring 6-O-sulfated glucosamine residues, but it was dependent on higher degrees of sulfation of oligosaccharides and indispensable N-substituted glucosamine adjacent to the cleavable linkage. Moreover, the enzyme demonstrated less preferential cleavage toward glycosidic linkages containing glucuronic acid than those containing iduronic acid of the counterpart oligosaccharides. Biolayer interferometry revealed differences in reactivity that are not completely consistent with different affinities of substrates to enzyme. Our study presented accurate information on the cleavage promiscuity of heparinase I that is crucial for heparin depolymerization.

Stability Profiles and Therapeutic Effect of Cu/Zn Superoxide Dismutase Chemically Coupled to O-Quaternary Chitosan Derivatives against Dextran Sodium Sulfate-Induced Colitis.

Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to O-quaternary chitosan derivatives (O-HTCC) to yield a polymer-enzyme conjugate O-HTCC-SOD that demonstrated superior therapeutic effect to native SOD. The present study demonstrated that O-HTCC-SOD had wider pH activity range, better thermal stability, excellent long-term stability for storage, as well as unique reinstatement of activity exposure to proteolytic degradation that was helpful for longer half-life in vivo. O-HTCC-SOD exerted significant anti-inflammatory effects on lipopolysaccharides (LPS)-stimulated mouse peritoneal macrophages by down-regulating production of pro-inflammatory cytokines and intracellular ROS. O-HTCC-SOD significantly attenuated dextran sodium (DSS)-induced colitis in mice as observed by the colitis severity, neutrophil infiltration and histopathological damage, whereas native SOD failed to do so. In conclusion, conjugation of O-HTCC conferred SOD with better stability and enhanced therapeutic potential, offering a promising option in treatment of inflammatory bowel disease.

A novel enzyme-free and label-free fluorescence aptasensor for amplified detection of adenosine.

A novel enzyme-free and label-free fluorescence aptasensor based on target-catalyzed hairpin self-assembly is developed for amplified detection of adenosine. This aptasensor contains four DNA strands termed as aptamer-catalysis strand, inhibit strand, hairpin structures H1 and H2 which are partially complementary. Meanwhile, a sequence that can form DNA G-quadruplex is partly hidden in the stem of H2. In the absence of adenosine, aptamer-catalysis strand is inhibited, and cannot trigger the self-assembly between H1 and H2. Upon the addition of adenosine, the binding event of aptamer and adenosine triggers the self-assembly between H1 and H2, resulting in the formation of G-quadruplex at the end of H1-H2 complex. The addition of N-methyl mesoporphyrin IX, which has a pronounced structural selectivity for G-quadruplex, generates label-free fluorescence signal. In the optimum conditions, we could detect adenosine as low as 6 µM by monitoring the change in fluorescence intensity. Furthermore, this amplified aptasensor shows high selectivity toward adenosine against its analogs due to the specific recognition ability of the aptamer for the target. Thus, the proposed aptasensor could be used as a simple and selective platform for target detection.

Anti-metastatic and anti-angiogenic activities of sulfated polysaccharide of Sepiella maindroni ink.

A previous study demonstrated that SIP-SII, a sulfated Sepiella maindroni ink polysaccharide, suppressed the invasion and migration of cancer cells via the inhibition of the proteolytic activity of matrix metalloproteinase-2 (MMP-2). Therefore, this study investigated the anti-metastatic effect of SIP-SII in vivo. SIP-SII (15 and 30 mg/kg d) markedly decreased B16F10 pulmonary metastasis in mice models by 85.9% and 88.0%, respectively. Immunohistochemistry showed that SIP-SII decreased the expression of the intercellular adhesion molecule 1 (ICAM-1) and basic fibroblast growth factor (bFGF) in lung metastasis nodules. In addition, SIP-SII inhibited neovascularization in chick chorioallantoic membrane assay at 0.08-2 mg/mL. In the in vitro experiments, SIP-SII (0.8-500 µg/mL) significantly decreased the protein and mRNA expression of ICAM-1 and bFGF in SKOV3 and EA.hy926 cells, respectively. These results suggested that SIP-SII might suppress melanoma metastasis via the inhibition of the tumor adhesion mediated by ICAM-1 and the angiogenesis mediated by bFGF, as well as resulting in depression of the invasion and migration of carcinoma cells.

Effect of Colla corii asini (E'jiao) on D-galactose induced aging mice.

Colla corii asini (E'jiao), donkey-hide gelatin prepared by stewing and concentrating from Equus asinus L. donkey hide, is a traditional Chinese medicine preparation widely used in clinical hematic antanemic therapy in China. The aim of the present study was to investigate potential anti-aging effect of Colla corii asini and explore related mechanisms in D-galactose (gal) induced aging model mice. The mice were artificially induced aging by subcutaneously injection with D-gal at the dose of 100 mg/kg·d for 8 weeks. Colla corii asini was simultaneously treated to them once daily by intragastric gavage. Appetite, mental condition, body weight, and organ index were observed. Activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), as well as levels of malondialdehyde (MDA) in serum, brain, and liver were determined by according assay kits. Western blotting analysis was used to detect p16 and p21 expression. Results indicated that Colla corii asini could improve appetite, mental condition, body weight, and organ condition of model mice, improve SOD, CAT, and GSH-Px activities, reduce MDA levels, and modulate age-related genes expression in D-gal induced mice. Therefore, Colla corii asini may have effect to suppress the aging process through enhancing antioxidant activity, scavenging free radicals, and modulating aging-related gene expression.

Enhanced anti-angiogenesis and anti-tumor activity of endostatin by chemical modification with polyethylene glycol and low molecular weight heparin.

Endostatin (ES), a potent endogenous angiogenesis inhibitor found in 1997 by O'Reilly, can effectively inhibit angiogenesis, inhibit the growth and metastasis of tumors. ES can also decrease drug resistance in long term and repeated treatment when it is used in combination with other chemotherapeutic agents. But there are still lots of obstacles on its clinical application, such as the need of a high dose to maintain its efficacy short half-life, poor stability, expensive, and some other shortcomings just like other protein drugs. Chemical modification on ES by polyethylene glycol (PEG) and low molecular weight heparin (LMWH) were successfully carried out in order to obtain a better ES derivative. Several classic experimental models were employed to study the bioactivity of ES and modified ES, including chicken chorioallantoic membrane (CAM) assay, corneal neovascularization (CNV) assay and Sarcoma 180 tumor bearing mice assay. The results showed that PEG-ES and LMWH-ES had better anti-angiogenesis and anti-tumor activity than ES, which indicates that LMWH was also a good protein modifier.

Novel C-4'' modified azithromycin analogs with remarkably enhanced activity against erythromycin-resistant Streptococcus pneumoniae: the synthesis and antimicrobial evaluation.

Three novel structural series of C-4'' modified azithromycin analogs with two amide groups, which were connected by different alkyl linkage, were designed, prepared and evaluated for their in vitro antibacterial activity against seven phenotypes of respiratory pathogens. Among them, 7d, 8j and 9j, as representatives of corresponding series, exhibited remarkably improved activity against erythromycin-resistant Streptococcus pneumoniae expressing the erm gene, the mef gene, and the erm and mef genes. In addition, 7a-c, 7f-h, 7j, 8d, 8g, 8i, 9a-b and 9i displayed favorable efficacy against erythromycin-resistant S. pneumoniae A22072 expressing the mef gene.

Synthesis and antibacterial activity of novel 4″-O-benzimidazolyl clarithromycin derivatives.

Novel 4″-O-benzimidazolyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These benzimidazolyl derivatives exhibited excellent activity against erythromycin-susceptible strains better than the references, and some of them showed greatly improved activity against erythromycin-resistant strains. Compounds 16 and 17, which have the terminal 2-(4-methylphenyl)benzimidazolyl and 2-(2-methoxyphenyl)benzimidazolyl groups on the C-4″ bishydrazide side chains, were the most active against erythromycin-resistant Staphylococcus pneumoniae expressing the erm gene and the mef gene. In addition, compound 17 exhibited the highest activity against erythromycin-susceptible S. pneumoniae ATCC49619 and Staphylococcus aureus ATCC25923 as well. It is worth noting that the 4″-O-(2-aryl)benzimidazolyl derivatives show higher activity against erythromycin-susceptible and erythromycin-resistant strains than the 4″-O-(2-alkyl)benzimidazolyl derivatives.

Efficacy of oral colon-specific delivery capsule of low-molecular-weight heparin on ulcerative colitis.

Low-molecular-weight heparin has the potential for the treatment of ulcerative colitis, and targeted drug delivery to the colon is important for topical treatment of this disease, so low-molecular-weight heparin oral colon-specific delivery capsule was prepared, and the in vitro and in vivo drug release behavior was investigated. The macroscopical and histological scoring systems, wet colon mass index and myeloperoxidase activity were assessed to evaluate the efficacy of the capsule after administered orally to experimental colitis mice. Serum levels, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and a link factor of blood coagulation and inflammation factor Xa (FXa) were assayed by enzyme-linked immunosorbent assay. The expression of Musashi-1 (as an intestinal stem cell marker) in the colons was assessed by immunohistochemical analysis. The in vitro and in vivo drug release studies clearly indicated that the specific coated capsules were capable of protecting low-molecular-weight heparin from releasing in stomach and small intestine, while specifically delivering at colon. The oral colon-specific delivery capsule of low-molecular-weight heparin could attenuate macroscopic and histological features of colitis. The results showed that low-molecular-weight heparin oral colon-specific delivery capsule significantly decreased the serum levels of TNF-α, IL-6 as well as FXa, while increased the expression of Musashi-1 in colon compared with acetic acid-induced ulcerative colitis model group. The results showed that low-molecular-weight heparin oral colon-specific delivery capsule had the potential for treatment of inflammatory bowel disease.

Synthesis and antibacterial activity of novel 4''-O-arylalkylcarbamoyl and 4''-O-((arylalkylamino)-4-oxo-butyl)carbamoyl clarithromycin derivatives.

Novel series of novel 4''-O-arylalkylcarbamoyl and 4''-O-((arylalkylamino)-4-oxo-butyl)carbamoyl clarithromycin derivatives were designed, synthesized and evaluated for their in vitro antibacterial activities. These derivatives retained excellent activity against the erythromycin-susceptible strains and showed significantly improved activity against all of the tested erythromycin-resistant strains. Among them, compound 4c was the most effective (0.06 microg/mL) against Streptococcus pneumonia encoded by the erm gene and compound 4a was had the most potent activity (0.25 microg/mL) against S. pneumonia encoded by the erm and mef genes.

Effect of low molecular weight heparin rectal suppository on experimental ulcerative colitis in mice.

The objective of this study was to investigate the effect and possible mechanism of rectally administered low molecular weight heparin (LMWH) on experimental ulcerative colitis. LMWH rectal suppository was prepared and its efficacy was studied by macroscopical and histological scoring systems as well as myeloperoxidase activity. Serum levels, including tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and a link factor of blood coagulation and inflammation factor Xa (FXa) were assayed by enzyme-linked immunosorbent assay. The expression of Musashi-1 (as an intestinal stem cell marker) in the colons was assessed by immunohistochemical analysis. The results showed that LMWH rectal suppository significantly decreased serum levels of TNF-α, IL-6 as well as FXa, while increased the expression of Musashi-1 in colon compared with acetic acid induced ulcerative colitis model group. All these preliminary results indicate LMWH rectal suppository is promising for treatment of ulcerative colitis.

A novel conjugate of low-molecular-weight heparin and Cu,Zn-superoxide dismutase: study on its mechanism in preventing brain reperfusion injury after ischemia in gerbils.

Low-molecular-weight heparin (LMWH) and Cu,Zn-superoxide dismutase (SOD) were extensively investigated on preventing brain reperfusion injury after ischemia (BRII) in the past few years and both exhibited some advantages as well as limits in practice. To explore whether chemical modification for LMWH and SOD can lead to improved bioactivity,in our present study, we examined the efficacy of LMWH conjugated SOD (LMWH−SOD) in the model of BRII gerbils. Ischemia/reperfusion was performed for 5 min by clamping the bilateral common carotid arteries of gerbils. LMWH−SOD, SOD and the mixture of LMWH and SOD (LMWH+SOD) were administered intravenously to corresponding animals just before ischemia. 24 h after reperfusion, serum malondialdehyde (MDA) content and SOD activity were measured, the expression of intercellular adhesion molecule-1 (ICAM-1) was examined by immunohistochemistry, and the brain sections were processed for Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling.The results showed that LMWH−SOD significantly lowered MDA content (P<0.001, versus SOD and LMWH+SOD) and elevated SOD activity (P<0.05, versus SOD and LMWH+SOD) in the serum of BRII gerbils. Immunohistochemical results indicated ICAM-1 positive staining was lighter, pyramidal cells of hippocampal CA1 region were more regular and the changes in cell edema were minor, and apoptosis of hippocampal cells was milder in LMWH−SOD treated animals than in SOD or LMWH+SOD treated animals, untreated BRII animals and sham-operated animals. The results suggest that the novel LMWH−SOD conjugate can inhibit upregulation of ICAM-1 and prevent neuronal cell apoptosis in BRII gerbils, and the LMWH−SOD conjugate has better anti-inflammatory and neuroprotective effects in BRII than native SOD and the mixture of LMWH and SOD.

The preventive effects of heparin-superoxide dismutase on carbon tetrachloride-induced acute liver failure and hepatic fibrosis in mice.

In this study, the effects of heparin-superoxide dismutase conjugate (heparin-SOD) on carbon tetrachloride (CCl4)-induced acute liver failure and hepatic fibrosis were evaluated. To investigate the effects of heparin-SOD on acute liver failure, heparin-SOD was administered to CCl4-treated mice by intravenous injection. Biochemical indicators, such as glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT), GSH (glutathione), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were determined 24 h after CCl4 treatment. The development of CCl4-induced acute liver failure altered the redox state with a decreased hepatic GSH and increased formation of lipid peroxidative products, which were partially normalized by treatment with heparin-SOD or heparin + SOD. Compared with other groups, the acute liver injury of heparin-SOD group was significantly lessened (reduced activities of GOT/GPT, MDA, and increased activities of GSH). To investigate the effects of heparin-SOD on hepatic fibrosis, heparin-SOD and CCl4 were co-administered by intraperitoneal injection twice a week for 12 weeks. Histological and hepatic hydroxyproline examination revealed that heparin-SOD could significantly prevent the progression of hepatic fibrosis. Moreover, real-time PCR was used to determine transforming growth factor-beta1 (TGF-beta1), metalloproteinase-2 (MMP-2), fibronectin, and collagen-I expression. Significantly, greater fibrosis and TGF-beta1, MMP-2, fibronectin, and collagen-I expression were found in the liver of CCl4-induced mice at the end of 12th week. Heparin-SOD could markedly attenuate the mRNA expression of TGF-beta1, MMP-2, and collagen-I. Western blots of tissue homogenates revealed that the protein expression of TGF-beta1 was substantially reduce also by heparin-SOD treatment. These results demonstrate that administration of heparin-SOD may be useful in the treatment and prevention of acute liver failure and hepatic fibrosis.

Attenuation effects of heparin-superoxide dismutase conjugate on bleomycin-induced lung fibrosis in vivo and radiation-induced inflammatory cytokine expression in vitro.

In this study, the effects of heparin-superoxide dismutase conjugate (heparin-SOD) on bleomycin-induced pulmonary fibrosis in vivo and on inflammatory cytokine expression in vitro were evaluated. To investigate the effects of heparin-SOD on pulmonary fibrosis, heparin-SOD was administered to bleomycin (BLM)-treated mice by intraperitoneal injection once a day and the hydroxyproline content in lung was determined per 7days. The degree of fibrosis was assessed quantitatively using histopathologic features. The results showed that heparin-SOD inhibited BLM-induced lung fibrotic lesions as reflected by the decrease of lung hydroxyproline content and lung fibrosis grade 28days after BLM instillation. The in vitro effects on the cytokine level expressed by irradiated 3T3 fibroblasts showed that heparin-SOD significantly lowered the levels of transforming growth factor-beta1 and interleukin-1beta. These results strongly demonstrated that heparin-SOD might be useful in the prevention and treatment of pulmonary fibrosis.

Expression of thymosin alpha1-thymopentin fusion peptide in Pichia pastoris and its characterization.

Thymopentin plays an important role in improving imbalanced immune systems of patients, however, it has a limited half-life in plasma. To get more stable and active thymopentin analogs, a fusion thymosin alpha1-thymopentin (Talpha1-TP5) gene was synthesized and cloned into vector pGAPZalphaA. Talpha1-TP5 fusion peptide was expressed in pichia pastoris and purified by metal chelating chromatography and gel filtration chromatography. The circular dichroism spectra (CD) indicated that the secondary structure of Talpha1-TP5 fusion peptide is dominated by a-helix and random coil. In vitro analysis showed that the plasma half-life of Talpha1-TP5 fusion peptide is 140 +/- 14 min, which is longer than that of TP5 (5.6+/-0.7 min) and Talpha1 (127+/-11 min). The in vitro activity assay presented that Talpha1-TP5 fusion peptide has greater activity in promoting proliferation of Kunming mouse splenocytes, and in vivo experiment it showed better activity in promoting the phagocytosis of macrophages and secretion of IL-2 than both Talpha1 and TP5. Our findings suggest that Talpha1-TP5 fusion peptide might be a potential therapeutic agent.

Characterization and secondary structure analysis of endostatin covalently modified by polyethylene glycol and low molecular weight heparin.

Endostatin (ES), as an angiogenesis inhibitor, has been approved by the State Food and Drug Administration (SFDA) in China for the treatment of patients with non-small-cell lung cancer. However, as a protein drug, there are a lot of obstacles on its clinical application, such as need of high dose to maintain its efficacy, expensive and poor stability, etc and limits its clinical use. In order to overcome these shortcomings, we chemically modified ES by polyethylene glycol and low molecular weight heparin (LMWH), respectively. The changes of the secondary structure of the modified products were studied by Fourier transform infrared spectroscopy and Circular dichroism spectra to obtain better ES derivatives. Our study demonstrated that the modified products have a better heat tolerance than ES towards. The result of secondary structure analysis suggests the percentage of beta-turn in whole protein is an important factor on the activity and heat stability and ES modified by LMWH can maintain higher activity and its secondary structure.

The relationship between the structure of dermatan sulfate derivatives and their antithrombotic activities.

To study the relationship between the structure of dermatan sulfate (DS) derivatives and their anti-thrombotic activities, DS-derived oligosaccharides (with different structures and relative molecular weight (M(r))) were prepared, and the effects of the DS-derived oligosaccharides on the activities of heparin cofactor II (HCII), activated protein C (APC), blood platelet, and vascular endothelial cells were studied. The major disaccharides of DS and polysulfated dermatan sulfate (PSDS) were IdoA-1-->3-GalNAc-4-OSO(3) and IdoA-2OSO(3)-1-->3-GalNAc4, 6-diOSO(3), respectively. The results showed that the consequence of the thrombotic inhibitory effects of DS and its derivatives were as follows: PSDS>low molecular weight polysulfated dermatan sulfate (LPSDS)>DS. Both DS and PSDS inhibited platelet aggregation in the concentration-dependent manner, and the IC(50) value of DS and PSDS is 12.7+/-1.3 and 28.6+/-0.9 mg/mL, respectively. DS oligosaccharides (DSOSs) and PSDS oligosaccharides (PSDSOSs) both significantly inhibited P-selectin expression on platelet surface (P<0.01), while DSOSs have no different effect compared with PSDSOSs. DSOSs and PSDSOSs significantly enhanced the activity of HCII in inhibiting thrombin in the plasma. The most active PSDSOS was PSDSOS(1) with M(r) of 4959, which enhanced the HCII activity by 91% (P<0.01). The experiments on APC activity showed that DS and its derivatives enhanced APC activity. The most active PSDSOS was PSDSOS(3) with M(r) of 2749, which enhanced the APC activity to 331+/-27% (P<0.01). DSOSs and PSDSOSs enhanced tissue plasminogen activator (t-PA) activity and reduced the plasminogen activator inhibitor (PAI) activity from cultured human umbilical vein endothelial cells (HUVEC), resulting in the ratio of t-PA/PAI going up. PSDSOSs which have the same M(r) as DSOSs produced more active effects in above assays, except for platelet aggregation.