bjectiveTo observe the effecacy of immunosuppressive agents on modulation of the disorders of inflammatory and antiinflammatory cytokines in acute pancreatitis, and to investigate the mechanism of treatment of acute pancreatitis with immunosuppressive agents. MethodsSD male rats were divided into 6 groups: group 1, the normal control group (n=6); group 2, acute pancreatitis induced by ductual injection of 5%sodium cholate sulfur at the volume of 1.0 ml/kg without treatment (n=8). After the pancreatitis were induced, the rest rats were injected intravenously with 5Fu 40 mg/kg (group 3, n=6); or methylprednisolone 30 mg/kg (group 4, n=6); or cyclophosphamide 20 mg/kg (group 5, n=6); or methotrexate 1.2 mg/kg (group 6, n=6). Twentyfour hours afteroperation, the animals were killed, the blood samples were taken for measurement of TNFα, IL1, IL6 (by bioassay), and IL10, TGFβ (by ELISA) as well as amylase. ResultsThe inflammatory cytokines (TNFα,IL1,IL6 ) and the antiinflammatory cytokines (IL10 and TGFβ), in blood of acute pancreatitis were increased significantly. After treated with immunosuppressive agents, both the inflammatory and antiinflammatory cytokines were decreased in different degrees. Some indexes of the severity of acute pancreatitis, such as amylase and pancreatic weight were improved obviously.ConclusionImmunosuppressive agents can regulate inflammatoryassociated cytokines increased remarkably in the acute pancreatitis. Therefore, improvement of acute pancreatitis can be achieved through rectifying the abnormal immunity and relieving the pathophysiological disorders of the acute pancreatitis by immunosuppressive agents.
In order to investigate the mechanism of enterogenous infection, sixty SD rats were randomly allocated into four groups∶ group of intestinal obstruction; group of cyclophosphamide+intestinal obstruction; group of cyclophosphamide and group of sham-operation. Each group included 15 rats. Twenty four hours after obstruction of the terminal ileum, the bacteria in blood of portal vein, blood of heart, peritoneal fluid, mesenteric lymph node (MLN) and content of gut were determined quantitatively, the concentration of endotoxin in portal system were measured. The results showed that early (24 hours) intestinal obstruction led to endotoxemia in portal vein, overgrowth of enteric G－bacili and bacterial translocation into the MLN. The immunosuppressive agent cyclophosphamide not only increased the rate of bacterial translocation into MLN and the number of living bacteria in MLN, but also promoted bacteria to spread into the systemic circulation. The authors conclude that under immunosuppression the bacterial translocation from gut by way of lymphatic channel plays an important role in enterogenous infection.
Objective To study the effect of low-dose cyclophosphamide (CY) on apoptosis of lung parenchyma cells in the early severe burn stage in rats. Methods Ninety clean SD male rats were randomly divided into 3 groups: the normal group (n=10), the experimental group (n=40) and the burn group (n=40). The model of degree III with 30% burn area was made in the experimental group and the burn group. CY (2 mg/kg) was injected into the abdominal cavity right after burn in the experimental group. No treatment was done in the normal group and burn group. Lung tissues were obtained at 3, 6, 12and 24 hours, respectively, after burn, and were observed by HE staining. Apoptosis of lung parenchyma cells was observed by TUNEL. Results Lung tissues were observed under the opticalmicroscopy in the normal group: the pulmonary structure was clear, and there were no inflammatory cells and exudation in the alveolar space and bronchial lumen. Besides, a few RBCs were seen. Pathological changes of lung tissues were observed under the opticalmicroscopy in the burn group: alveolar septum was obviously widened; alveolar wall was destroyed; interstitial edema and atelectasis occurred; and pathological lesion was gradually aggravated as time passed by. The pathological lesion of lung tissues mentioned above in the experimental group was better than those in the burn group. Compared with the normal group, the apoptosis ratio of lung parenchyma cells continuously increased in the burn group from the 3 hour after burn, and reached the peak at 12 hours. There were significant differences between the two groups (P lt; 0.05). However, in the experimental group, the apoptosis ratio of lung parenchyma cells increased at 3 hours after burn, cut down to normal at 6 and 12 hours, respectively, and notably decreased at 24 hours. There were significant differences between the experimental group and the normal group (P lt; 0.05). Compared with the burn group, the apoptosisrate of lung parenchyma cells in the experimental group began to decrease strikingly from the 6 hours after burn, and there were significant differences between the two groups (P lt; 0.05). Conclusion Low-dose CY can restrain the apoptosis of lung parenchyma cells in the early severe burn stage in rats and alleviate the injury of the lung.
Objective To assess the clinical effectiveness and safety of fludarabine and cyclophosphamide (FC) combined with rituximab chemotherapy regimen (FCR regimen) for patients with chronic lymphoblastic leukemia (CLL). Methods The databases such as PubMed, The Cochrane Library, SpringerLink, CNKI, and CBM were searched from 2000 to 2011. The randomized controlled trials (RCTs) on FC regimen versus FCR regimen for CLL were retrieved. The methodological quality of the included studies was assessed according to the Cochrane Reviewer’s Handbook, and meta-analyses were performed using RevMan 5.0 software. Results Three RCTs involving 1 623 patients with CLL were included. The results of meta-analyses showed that significant differences were found in the progression-free survival (PSF)(Plt;0.001), overall response (OR=1.94, 95%CI 1.49 to 2.53, Plt;0.000 01), complete remission (OR=2.54, 95%CI 2.00 to 3.22, Plt;0.000 01), and grade III or IV neutropenia (OR=1.60, 95%CI 1.33 to 1.92, Plt;0.000 01); but no significant differences were found in the partial response (OR=0.74, 95%CI 0.35 to 1.55, P=0.43), grade III or IV thrombocytopenia (OR=0.97, 95%CI 0.74 to 1.27, P=0.83) and autoimmune hemolytic anemia (OR=0.86, 95%CI 0.59 to 1.27, P=0.45) between FCR and FC regimen. Conclusion The FCR regimen can improve the progression-free survival, overall response and complete remission. Meanwhile, it sometimes increases the incidence of Grade III or IV events, such as neutropenia, thrombocytopenia, autoimmune hemolytic anemia and nausea and vomiting.
Objective To assess the effects of combining intravenous immunoglobulin for systemic lupus erythematosus (SLE) by analyzing the randomized controlled trials (RCT). Methods The electronic databases such as PubMed (1966 to Aug. 2010), EMbase (1974 to Aug. 2010), The Cochrane Library (Issue 2, 2010), CNKI (1994 to Aug. 2010), VIP (1989 to Aug. 2010), CBM (1978 to Aug. 2010) and Chinese Medical Association Digital Periodicals (1998 to Aug. 2010) were searched to collect RCTs of intravenous immunoglobulin for the patients with SLE. The methodology quality of the included studies was evaluated in accordance with RCTs quality evaluation standard of the Cochrane Handbook 4.2.6, and meta-analyses were performed by using RevMan 5.0 software. Results Four RCTs involving 154 participants were included. The results of meta-analyses showed that compared with cyclophosphamide pulse therapy, the combining intravenous immunoglobulin markedly reduced the SLE disease activity index (MD= –3.09, 95%CI –4.21 to –1.97), the incidence of infection (OR=0.24, 95%CI 0.11 to 0.54), the proteinuria (MD= –1.09, 95%CI –2.11 to –0.06), and the relapse of SLE (OR=0.07, 95%CI 0.01 to 0.37). But there was no significant difference in elevating of complement between two groups. Conclusion According to the results of meta-analyses, compared with cyclophosphamide pulse therapy, cyclophosphamide combining intravenous immunoglobulin may be more efficient in improving clinical symptoms, decreasing incidence rate of infectious diseases, and reducing relapse for SLE patients.
Objective To assess the efficacy and safety of mycophenolate mofetil (MMF) versus cyclophosphamide (CTX) in the induction treatment for lupus nephritis (LN). Methods Such databases as MEDLINE, EMBASE, SCIE, The Cochrane Library, the Cochrane Controlled Trials Register, CBM, and CNKI were searched from their establishment date to August of 2010 to retrieve the randomized controlled trials (RCTs) about MMF versus CTX for LN. The methodology quality of included studies was evaluated. The efficacy indexes i.e. the clinical total remission (TR), complete remission (CR), partial remission (PR), pathological activity index, the chronicity index and complete induction therapy rate (CIR), and the safety indexes i.e. the rate of patient intolerance-to-drug, the incidence of infection, leukopenia and diarrhea, were abstracted. Finally the Meta-analyses were conducted by using Cochrane Collaboration’s RevMan 4.2. Results Eight RCTs involving 773 patients met the inclusive criteria. The results of meta-analyses showed that the total remission rate (OR=1.49, 95%CI 1.10 to 2.02) and complete remission rate (OR=1.67, 95%CI 1.08 to 2.57) were significantly higher in the MMF group than the CTX group. There was no significant difference in the rate of partial remission, the complete induction rate, the rate of patient intolerance-to-drug, the incidence of infection and leukopenia. However, the incidence of diarrhea was higher in the MMF group (OR=2.99, 95%CI 1.87 to 4.78). The results of meta-analyses for type IV LN were the same. Conclusion MMF is superior to CTX in the induction therapy to Lupus Nephritis (type III, IV, V), but the incidence of diarrhea is higher.
ObjectiveTo systematically review the efficacy and safety of mycophenolate mofetil (MMF) for Henoch-Schonlein purpura nephritis (HSPN). MethodsDatabases such as PubMed, EMbase, CENTRAL, VIP, CNKI, CBM and WanFang Data were electronically searched for comprehensively collecting the randomized controlled trials (RCTs) on the efficacy and safety of MMF for HSPN from inception to December, 2013. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.1 software. ResultsA total of 10 RCTs involving 426 patients (231 in the trial group and 195 in the control group) were included. The trial group was treated with MMF and corticosteroids, and the control group was treated with corticosteroids monotherapy or combined with cyclophosphamide (CTX), leflunomide (LEF), or azathioprine (AZA). The results of meta-analysis showed that, as for efficacy, no significant difference was found between the two groups after six-mouth treatment (OR=1.36, 95%CI 0.67 to 2.73, P=0.85), while after twelve-mouth treatment, MMF was superior to CTX with a significant difference (OR=6.58, 95%CI 2.45 to 17.33, P=0.002). In addition, the efficacy of MMF was still superior to the azathioprine group, but not better than either LEF or prednisone monotherapy. Lower incidence of side effects were found in the MMF group, compared with the CTX group (OR=0.25, 95%CI 0.13 to 0.45, P < 0.000 01) and the prednisone monotherapy group (OR=0.26, 95%CI, 0.09 to 0.79, P=0.02), while there was no significant difference between the MMF group and the LEF group in side effects. ConclusionBased on the current evidence, the efficacy of MMF for HSPN is better than CTX, and its side effects are less than those of CTX and prednisone.