Objective: To explore the expulsion effect of sodium dimercaptopropanesulfonate (DMPS) on mercury in different organs of mercury poisoning and the therapeutic effect of glutathione (GSH) combined with antioxidant therapy on mercury poisoning. Methods: In February 2019, 50 SPF male SD rats were randomly divided into 5 groups, 10 rats in each group: A (saline negative control group) , B (HgCL2 positive control group) , treatment group (C: intramuscular injection of DMPS 15 mg/kg treatment, D: intramuscular injection of DMPS30 mg/kg treatment, E: intramuscular injection of DMPS 15 mg/kg and intraperitoneal injection of GSH200 mg/kg treatment) . Rats in group B, C, D and E were subcutaneously injected with mercury chloride solution (1 mg/kg) to establish a rat model of subacute mercury poisoning kidney injury. Rats in group A were subcutaneously injected with normal saline. After the establishment of the model, rats in the treatment group were injected with DMPS and GSH. Rats in group A and group B were injected with normal saline. At 21 d (treatment 7 d) and 28 d (treatment 14 d) after exposure, urine and blood samples of 5 rats in each group were collected. Blood biochemistry, urine mercury, urine microalbumin and mercury content in renal cortex, cerebral cortex and cerebellum were detected. Results: After exposure to mercury, the contents of mercury in renal cortex, cerebrum and cerebellum of rats in group B, C, D and E increased, and urine microalbumin increased. Pathology showed renal tubular injury and renal interstitial inflammation. Compared with group B, urinary mercury and renal cortex mercury in group C, D and E decreased rapidly after DMPS treatment, and there was no significant decrease in mercury levels in cerebellum and cerebral cortex of rats, accompanied by transient increase in urinary albumin after DMPS treatment (P<0.05) ; the renal interstitial inflammation in group E was improved after GSH treatment. There was a positive correlation between urinary mercury and the contents of mercury in renal cortex, cerebral cortex and cerebellum (r=0.61, 0.47, 0.48, P<0.05) . Conclusion: DMPS mercury expulsion treatment can significantly reduce the level of metal mercury in the kidney, and there is no significant change in the level of metal mercury in the cortex and cerebellum.
Animals ; Brain/drug effects* ; Glutathione ; Inflammation ; Kidney/drug effects* ; Kidney Diseases/chemically induced* ; Male ; Mercuric Chloride/therapeutic use* ; Mercury/urine* ; Mercury Poisoning/drug therapy* ; Rats ; Rats, Sprague-Dawley ; Saline Solution/therapeutic use* ; Unithiol/therapeutic use*

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.
Administration, Oral ; Adolescent ; Chelating Agents ; administration & dosage ; adverse effects ; therapeutic use ; Chelation Therapy ; adverse effects ; methods ; Child ; Copper ; urine ; Drug Administration Schedule ; Drug Hypersensitivity ; etiology ; Drug Therapy, Combination ; Hepatolenticular Degeneration ; drug therapy ; Humans ; Injections, Intravenous ; Male ; Neutropenia ; chemically induced ; Partial Thromboplastin Time ; Penicillamine ; administration & dosage ; adverse effects ; therapeutic use ; Prothrombin Time ; Thrombocytopenia ; chemically induced ; Time Factors ; Treatment Outcome ; Unithiol ; administration & dosage ; adverse effects ; therapeutic use

BACKGROUND/AIMS: Gastric mucus should be removed before endoscopic examination to increase visibility. In this study, the effectiveness of premedication with pronase for improving visibility during endoscopy was investigated. METHODS: From April 2010 to February 2011, 400 outpatients were randomly assigned to receive endoscopy with one of four premedications as follows: dimethylpolysiloxane (DMPS), pronase and sodium bicarbonate with 10 minutes premedication time (group A, n=100), DMPS and sodium bicarbonate with 10 minutes premedication time (group B, n=100), DMPS, pronase and sodium bicarbonate with 20 minutes premedication time (group C, n=100), and DMPS and sodium bicarbonate with 20 minute premedication time (group D, n=100). One endoscopist, who was unaware of the premedication types, calculated the visibility scores (range, 1 to 3) of the antrum, lower gastric body, upper gastric body and fundus. The sum of the scores from the four locations was defined as the total visibility score. RESULTS: Group C showed significantly lower scores than other groups (p=0.002). Group C also had the lowest frequency of flushing, which was significantly lower than that of group D. Groups C and D had significantly shorter durations of examination than groups A and B. CONCLUSIONS: Using pronase 20 minutes before endoscopy significantly improved endoscopic visualization and decreased the frequency of water flushing.
Dimethylpolysiloxanes ; Endoscopy ; Flushing ; Humans ; Mucous Membrane ; Mucus ; Outpatients ; Premedication ; Pronase ; Sodium Bicarbonate ; Unithiol

OBJECTIVE: To explore the effective treatment and prognostic factors for fulminant Wilson's disease (FWD). METHODS: We retrospectively analyzed the clinical characteristics, therapeutic Methods and outcomes of 13 FWD patients. We investigated the treatment effect of the joint use of hormones, decoppering, and plasma exchange therapy in patients with FWD, compared the difference in the clinical features, biochemical data and treatment between the survival group and the death group. RESULTS: Thirteen patients with FWD presented with acute hepatic failure and severe jaundice: 7 accompanied with severe hemolytic anemia, 5 with primary peritonitis, 8 with hepatic encephalopathy. Prothrombin activity (PTA) of 5 was below 30% in the 13 patients. Plasma exchange (PE), dimercaptopropansulfonate sodium (DMPS) and short-term methylprednisolone /dexamethasone administration were performed in 7 patients, in which 6 survived and the other 1 who had primary peritonitis with PTA below 30% died. The other 6 patients without above-mentioned treatments all died, in which 4 accompanied with primary peritonitis with PTA all below 30%. CONCLUSION The level of hepatic failure and the occurrence of infection are the decisive factors for prognosis of patients with FWD. PE with decoppering treatment and corticosteroid administration are effective.
Chelating Agents ; therapeutic use ; Combined Modality Therapy ; Copper ; blood ; Female ; Hepatolenticular Degeneration ; therapy ; Humans ; Male ; Methylprednisolone ; therapeutic use ; Plasma Exchange ; methods ; Prognosis ; Retrospective Studies ; Unithiol ; therapeutic use

OBJECTIVETo investigate the expression of angiotensin converting enzyme (ACE) and ACE2 Gene in lung of paraquat poisoning rats and the protection of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODSOne hundred SD male rats were randomly equally divided into 4 groups:normal control group (10 rats), drug control group (40 rats), paraquat poisoning group (40 rats) and drug intervention group(40 rats). The paraquat poisoning and drug intervention group rats were injected intraperitoneally by paraquat (20 mg/kg). The rats in drug intervention group rats were protected by intraperitoneal injection with Na-DMPS (200 mg/kg) 15 min before exposure of paraquat. Behavioral changes of the rats and histological changes of lung tissues under light microscope were observed. And the expression of ACE and ACE2 mRNA in lung tissues of rats both in paraquat poisoned group and drug intervention group were measured by RT-PCR at different time of 6 h, 24 h, 3 and 7 d after poisoning.

RESULTSThe poisoning symptoms of shortness of breath, cramps appeared and deteriorated progressively in rats after paraquat exposure and the protection of NA-DMPS could delay and reduce these symptoms significantly. Histological appearance of disorganization of pulmonary capillary and alveolus, exudation in alveolar space, pulmonary edema, severe bleeding, and inflammatory cells infiltration were obvious in lungs of rats after paraquat poisoning, whereas the histological changes were extenuated by protection of NA-DMPS. As compared with normal control group (NC group), the expressions of ACE, ACE2 mRNA in lung tissue decreased, and the lowest level of ACE mRNA expressions appeared at 24 h (0.457 +/- 0.262), on 3 d (0.385 +/- 0.179) after Paraquat exposure (P < 0.05), while lowest level of ACE2 mRNA expressions appeared on 3 d (0.415 +/- 0.247), 7 d (0.365 +/- 0.215) (P < 0.05). As compared with paraquat poisoned group, the expressions of ACE mRNA in lung tissue of rats in NA-DMPS protected group increased significantly at 24 h (0.739 +/- 0.558) and 3 d (0.749 +/- 0.414) (P < 0.05), while the expressions of ACE2 mRNA increased markedly on 3 d (0.584 +/- 0.345) and 7 d (0.493 +/- 0.292) (P < 0.05). But the expression of ACEmRNA and ACE2 mRNA in lungs had no statistical significance between normal control group and drug intervention group (P > 0.05).

CONCLUSIONThe expressions of ACE and ACE2 mRNA in lung tissue of the rats with paraquat poisoning are decreased. Na-DMPS can effectively improve the balance of RAS in local lung tissue and reduce the pathological changes of lung tissue, delay the poisoning symptoms and show protective effects for acute lung injury induced by paraquat.

Animals ; Lung ; drug effects ; enzymology ; Male ; Paraquat ; poisoning ; Peptidyl-Dipeptidase A ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Unithiol ; pharmacology

OBJECTIVEto investigate the changes of γ-aminobutyric acid (GABA) and glutamate (Glu) in the cerebral cortex following acute bromoxynil intoxication in mice and the protective effect of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODS30 ICR mice were randomly divided into blank control group (10), exposure group (10) and Na-DMPS protection group (10). The levels of GABA and Glu in the cerebral cortex were measured by RP-HPLC. The glutamine (Gln) level and the glutamine synthetase (GS), glutamate decarboxylation enzyme (GAD), γ-aminobutyric acid transaminase (GABA-T) activity in the cerebral cortex were determined by UV colorimetric.

RESULTScompared with the control group [GABA: (3.41 ± 0.12) micromol/g, Glu (14.00 ± 0.16) micromol/g, Gln (1.25 ± 0.19) micromol/g, GAD (13.50 ± 0.25) micromol × g(-1) × h(-1), GABA-T (25.51 ± 0.21) micromol × g(-1) × h(-1), GS(142.19 ± 1.31) U/mg pro], the level of GABA [(3.14 ± 0.14) micromol/g] was decreased (P < 0.05), whereas the level of Glu [(17.54 ± 0.40) micromol/g] and Gln [(3.35 ± 0.27) micromol/g] were increased (P < 0.05), the activity of GAD [(11.93 ± 0.15 micromol × g(-1) × h(-1)], GABA-T [(24.15 ± 0.22) micromol × g(-1) × h(-1)], GS [(140.75 ± 1.01) U/mg pro] was decreased (P < 0.05) in acute intoxication group; Compared with the acute intoxication group, the level of GABA [(3.52 ± 0.30) micromol/g] was increased (P < 0.05), whereas the level of Glu [(14.20 ± 0.32) micromol/g] and Gln [(1.32 ± 0.17) micromol/g] were decreased (P < 0.05), the activity of GAD [(13.01 ± 0.45 micromol × g(-1) × h(-1)], GABA-T [(25.19 ± 0.26) micromol × g(-1) × h(-1), GS [(142.35 ± 1.20) U/mg pro] was increased (P < 0.05); In contrast, the levels of GABA, Glu, Gln and the activity of GAD, GABA-T, and GS in Na-DMPS protection group were not significantly different in comparison with control group (P > 0.05).

CONCLUSIONthe central toxic effects of mice with acute bromoxynil intoxication may be related to the changes of GABA and Glu content in the cerebral cortex;Na-DMPS can protect mice from bromoxynil-induced central toxic effects and GABA and Glu abnormal change in the cerebral cortex.

Animals ; Cerebral Cortex ; drug effects ; metabolism ; Female ; Glutamic Acid ; metabolism ; Male ; Mice ; Mice, Inbred ICR ; Nitriles ; poisoning ; Toxicity Tests, Acute ; Unithiol ; pharmacology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVEto study the oxidative stress of rats with acute paraquat poisoning and the intervention of Sodium Dimercaptopropane Sulfonate (NA-DMPS).

METHODSEighty male SD rats were randomizedly divided into: the normal control group (n=8), NA-DMPS control group (n=8), the PQ group (n=32, the rats were intraperitoneally injected with 1% PQ solution at the dosage of 20 mg/kg) and the NA-DMPS protected group (n=32). The rats in the groups of normal and NA-DMPS control were sacrificed 1d after administration of NS or NA-DMPS. And the rats in the PQ group and the NA-DMPS protected group were sacrificed at 6h, 1, 3, 7d after poisoning. Samples of serum, bronchoalveolar lavage fluid (BALF) and lung tissue were gathered. The MDA and CAT in serum, BALF and lung homogenate, the glutathione (GSH) in serum and BALF were measured. And the expression of Nuclear factor E2-related factor 2 (Nrf2) mRNA in lung was tested with RT-PCR.

RESULTSCompared with the normal control group, the activities of MDA and CAT in serum, BALF and lung homogenate are higher in both groups of PQ and NA-DMPS protected. And compared with the PQ group, the activities of MDA in serum, BALF and lung homogenate of the NA-DMPS protected group decreased significantly at 6h, 1d after poisoning, whereas the activities of CAT are higher at 6h, 1, 3d in serum and 1, 3d in BALF and lung homogenate (P<0.05 or P<0.001). The serum GSH at 6h, 3d of the NA-DMPS protected group [(730.07 +/- 16.23), (793.66 +/- 7.40)] were higher than those in the PQ group. And the BALF GSH at 1, 3d of the NA-DMPS protected group [(609.75 +/- 6.74), (631.83 +/- 12.03)] were also markedly higher than the PQ group (P<0.05 or P<0.001). The expression of NRF2 mRNA of the lung at 1, 3, 7d in the PQ group [(0.71 +/- 0.061), (1.023 +/- 0.158), (0.969 +/- 0.046)] and the NA-DMPS protected group [(1.005 +/- 0.06), (1.464 +/- 0.166), (1.066 +/- 0.191)] were significantly higher than those in the control groups. Compared with the PQ group, the expression of NRF2 mRNA of the lung increased markedly in the NA-DMPS protected group at 1, 3d (P<0.01).

CONCLUSIONNa-DMPS decreases the activity of MDA and increases the activity of CAT, GSH and the expression of Nrf2 mRNA. NA-DMPS can protected rats from PQ intoxication by improving the balance of redox reaction.

Acute Disease ; Animals ; Male ; Oxidative Stress ; drug effects ; Paraquat ; poisoning ; Rats ; Rats, Sprague-Dawley ; Unithiol ; pharmacology

OBJECTIVETo observe the expression and effect of thrombomodulin (TM) mRNA and endothelial protein C receptor (EPCR) mRNA in lung tissue of acute paraquat poisoned rats, and intervention of sodium dimercaptopropane sulfonate (Na-DMPS).

METHODSEighty male SD rats were randomizedly divided into four groups: the normal control group (n=8), the Na-DMPS control group (n=8, administered with 200 mg/kg Na-DMPS intraperitoneally), the PQ group (n=32, administered with 20 mg/kg 1% PQ intraperitoneally), the NA-DMPS protected group (n=32, administered with 200 mg/kg Na-DMPS intraperitoneally before with 20 mg/kg 1% PQ). The expression of TM mRNA and EPCR mRNA in the PQ group and the Na-DMPS protected group was evaluated at the six hour, on the first, third and seventh day.

RESULTSThe expression of TM mRNA and EPCR mRNA in lung tissue of poisoned rats, was significantly increased and reached the peak at the six hour, was decreased slowly on the first day, and returned to normal level on the seventh day. In the Na-DMPS protected group, at the six hour and on the first day, the expression of TM mRNA (1.071 +/- 0.097, 1.055 +/- 0.051) was less than that in the PQ group (P<0.05 or P<0.01). EPCR mRNA (0.678 +/- 0.005), (0.650 +/- 0.007) at the six hour and on the first day in the Na-DMPS protected group was less than that in the PQ group (P<0.05 or P<0.01).

CONCLUSIONThe expression of TM mRNA and EPCR mRNA of rats after PQ intoxication is increased, and can significantly be decreased after administered with Na-DMPS.

Animals ; Antigens, CD ; genetics ; metabolism ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Paraquat ; poisoning ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; genetics ; metabolism ; Thrombomodulin ; genetics ; metabolism ; Unithiol ; therapeutic use

Animals ; Bridged-Ring Compounds ; poisoning ; Disease Models, Animal ; Female ; Male ; Mice ; Sodium Oxybate ; therapeutic use ; Unithiol ; therapeutic use

OBJECTIVETo observe the effect of Gandou Decoction IV (GDIV) on serum indexes of hepatic fibrosis and liver function in patients with Wilson's disease (WD).

METHODSSixty-one WD patients were assigned to two groups, 30 patients in the sodium dimercaptosulphonate (DMPS) group and 31 patients in the GD IV group. Both groups received 8 courses of DMPS treatment with 6 days as one course, and the GD IV group was given GD IV additionally. Serum indexes of liver function were examined, serum matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were detected by double antibody sandwish ABC enzyme-linked immunosorbent assay (ELISA), and serum hyaluronic (HA), laminin (LN), procollagen III (PC III) and collagen type IV (C-IV) were determined by radioimmunoassay (RIA).

RESULTSAfter treatment, all indexes of hepatic fibrosis and liver function had no significant change in the DMPS group, while in the GD IV group, the serum TIMP-1 level markedly decreased (P <0.05), the ratio of MMP-1/TIMP-1 significantly increased (P <0.01), and serum indexes of liver function markedly decreased (P < 0.05), but the changes in serum levels of HA, LN and PCIII, as well as in serum MMP-1 and C-IV were insignificant (P> 0.05), though they showed a trend of decreasing or increasing, respectively.

CONCLUSIONShort-term decopper-ing treatment with DMPS alone has no significant effect on hepatic function and serum fibrosis indexes in WD patients, while combined with GD IV, it can improve liver function and display an anti-fibrosis effect through inhibiting the serum TIMP-1 level and increasing the ratio of MMP-1/TIMP-1.

Adolescent ; Adult ; Chelating Agents ; therapeutic use ; Child ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; therapeutic use ; Hepatolenticular Degeneration ; blood ; drug therapy ; Humans ; Liver Cirrhosis ; blood ; prevention & control ; Matrix Metalloproteinase 1 ; blood ; Phytotherapy ; Tissue Inhibitor of Metalloproteinase-1 ; blood ; Unithiol ; pharmacology ; therapeutic use ; Young Adult