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Aim To investigate the role of P2X7 recep-tor and its mediated NLRP3 inflammatory signaling pathway in alcohol-induced liver injury. Methods The acute alcoholic liver injury model was established by NIAAA method, and thirty C57BL/6 male mice were randomly divided into three groups (n =10):control group, model group, A438079 group, The three groups were processed as follows in the last week:control group and model group: given an equal dose of saline intraperitoneal injection(about 0.2 mL/only) once a day. According to the weight of the mice, A438079 group was given intraperitoneally injection by 200 μmol·kg-1of A-438079 (prepared at 7 g·L-1 of A438079,about 0.2 mL/only) once a day. And it was given a single 31.5% alcohol solution by intragas-tric administration on the last day of the morning,with the dose of 10 mL·kg-1. Nine hours later alanine aminotransferase (ALT), aspartate aminotransferase (AST),cholesterol(TCHO),triglyceride(TG) were measured by orbital blood in mice. HE staining was used to observe the pathological changes of the liver. Immunohistochemical method was applied to detect the expression of P2X7R in liver tissues. Western blot was employed to detect the levels of P2X7R, NLRP3, ASC, IL-1β and IL-18 in liver tissues. Results Compared with control group,the levels of ALT,AST, TG and TCHO in model group were significantly en-hanced, and the liver injury was obvious. Compared with model group, the levels of ALT, AST, TG and TCHO in A438079 group significantly decreased. Compared with control group, the expressions of P2X7, NLRP3, ASC, IL-1β, IL-18 in model group were significantly higher than those in control group. Compared with model group, the expression levels of P2X7, NLRP3, ASC, IL-1β and IL-18 in A438079 group significantly decreased. Conclusion Alcohol-induced liver injury may be associated with P2X7R-NLRP3 signaling pathway.
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Objective To investigate theprognostic factors and prognostic value of acute organophosphorus pesticide poisoning. Methods Patients with acute organophosphorus pesticide from January 2009 to January 2017 in Cangzhou city emergency center from poisoning, describing the demographic characteristics, and clinical characteristics and prognosis of poisoning, using Logistic regression model analysis of admission when white blood cell count (WBC) , cholinesterase (ChE), lactic acid (Lac), blood glucose (GLU), serum myocardial enzymes (CK) and acute physiology and chronic health score (APACHE score) effects on the prognosis of patients, using Logistic regression probability prediction model and ROC curve analysis of the value of the index prediction on the prognosis of the patients. Results A total of 519 patients with acute organophosphorus pesticide poisoning were treated, the ratio of male to female was 1 :1.21 (235/284), the age was 20-50 years old (73.41%), mainly for farmers (64.74%), and the cause of poisoning was suicide (73.99%) . 87.09% patients were cured or improved, healed or dead patients accounted for 12.52%, accounting for 0.39% of the other. WBC (OR=5.056, 95% CI:1.714~14.915) , ChE (OR=5.190, 95% CI:1.396 ~ 19.298) , Lac (OR=5.124, 95% CI:1.347 ~ 19.497) , APACHE score (OR=10.098, 95% CI:1.311 ~ 77.767) is a risk factor for the prognosis of patients with organophosphorus poisoning. Logistic regression probability prediction results P=0.52, AUC:0.717 (95%CI:0.677~0.901), sensitivity: 0.70, specificity: 0.91, Kappa value: 0.460. The ROC curve was established by the APACHE II score alone, and the APACHE II score was 17.5 points, and AUC: 0.987 (95%CI:0.977~0.998), sensitivity: 0.99, specificity: 0.88, Kappa value: 0.543. Conclusion The scores of WBC, ChE, Lac and APACHE II were the prognostic factors of organophosphate poisoning. The predictive effect of the APACHE II score alone was better than that of WBC, ChE, Lac and APACHE II scoring.
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<p><b>BACKGROUND</b>While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection.</p><p><b>METHODS</b>An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package.</p><p><b>RESULTS</b>In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P < 0.05). In further paired comparisons of the CSSSI group vs. modeling control/sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P < 0.05), whereas sodium hyaluronate vs. sinomenine hydrochloride comparison failed to reach significance (P > 0.05).</p><p><b>CONCLUSIONS</b>CSSSI has a sustained-release effect on sinomenine hydrochloride. Intra-articular injection of CSSSI was significantly better than the sole sodium hyaluronate or sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.</p>
Subject(s)
Animals , Male , Rabbits , Hyaluronic Acid , Therapeutic Uses , Injections, Intra-Articular , Morphinans , Therapeutic Uses , Osteoarthritis , Drug Therapy , Random AllocationABSTRACT
<p><b>OBJECTIVE</b>To explore the penetrability and therapeutic effect of vancomycin to the prostates of rats with bacterial prostatitis (BP) or benign prostate hyperplasia (BPH)-BP.</p><p><b>METHODS</b>The experimental rats with BP or BPH-BP were injected with vancomycin through the tail vein. The prostate tissues and sera were isolated respectively from the rats at 10 min to approximately 24 h after treatment and the antibiotic activities of the samples were detected by serial dilution test and agar diffusion test. The rats with BP or BPH-BP were treated with vancomycin by intravenous injection daily for 5 days. The prostates were collected the second day after injection and bacteria were isolated and determined. One to five weeks after treatment, the prostates of the animals were isolated and pathologic tests were done.</p><p><b>RESULTS</b>No bacteria could be isolated from the prostates of the normal rats, but positive isolation was achieved from the prostates of the infected animals 28th day after infection. In the first 4 days after treatment, a decrease of bacteria could be detected in the prostate samples of the rats treated with BP or BPH-BP. After 5th day, no bacteria could be detected from 91.7% prostates of the treated groups. Obvious antibiotic activity in both sera and prostates could be detected 10 to approximately 150 min after the antibiotic injection. Antibiotic activity of the prostate tissues could be lower or higher than or equal to that of the sera in the same period. Pathologic tests detected obvious exudation and leukocyte invasion in the prostate tissues of the BP rats and gland proliferation in the BPH rats. Vancomycin treatment and the consequent reduction of bacteria obviously alleviated the inflammatory pathological changes in the prostates of the BP rats.</p><p><b>CONCLUSION</b>Vancomycin given intravenously has more penetrability to the prostates of either BP or BPH-BP rats. The antibiotic concentration in the prostate tissues may be equal to or higher than that of the sera, so that the susceptive bacteria in the prostates will be killed and the alleviation of the inflammation and repair of the tissues accelerated effectively.</p>