ABSTRACT
BACKGROUND: Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains. METHODS: The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured. Liver histopathology was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury. RESULTS: Compared with wild-type mice, the liver function indices and inflammation factors presented no significant difference in the Mif-/- mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1ß were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, mRNA levels of TNF-α, IL-1ß and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice. CONCLUSIONS: In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis.
Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Macrophage Migration-Inhibitory Factors , Sepsis , Animals , Gene Knockout Techniques , Lipopolysaccharides/toxicity , Liver , Macrophage Migration-Inhibitory Factors/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , Tumor Necrosis Factor-alpha/geneticsABSTRACT
BACKGROUND: Rabies is a serious reemerging zoonosis in China. At present human rabies cases are primarily diagnosed based on clinical presentation. CASE PRESENTATION: In August 2012, a woman and her son were attacked by a stray dog in Henan, China. The son received rabies postexposure prophylaxis (wound treatment followed by vaccine, no immunoglobulin), however, the mother did not. Rabies infection was subsequently laboratory confirmed in the mother and she died in December; her son is alive and healthy after 2 years of follow-up. CONCLUSION: This report documents that the timely utilization of postexposure prophylaxis is a required measure in preventing rabies after exposure to an animal bite.
Subject(s)
Bites and Stings/etiology , Post-Exposure Prophylaxis/statistics & numerical data , Rabies Vaccines/administration & dosage , Rabies virus/physiology , Rabies/drug therapy , Adult , Animals , Child , China , Dog Diseases/virology , Dogs , Fatal Outcome , Female , Humans , Male , Rabies/immunology , Rabies virus/geneticsABSTRACT
OBJECTIVE: To evaluate the application value of serum CA19-9, CEA, CA125 and CA242 in diagnosis and prognosis of pancreatic cancer cases treated with concurrent chemotherapy. MATERIALS AND METHODS: 52 patients with pancreatic cancer, 40 with benign pancreatic diseases and 40 healthy people were selected. The electrochemiluminescence immunoassay method was used for detecting levels of CA19-9, CEA and CA125, and a CanAg CA242 enzyme linked immunoassay kit for assessing the level of CA242. The Kaplan-Meier method was used for analyzing the prognostic factors of patients with pancreatic cancer. The Cox proportional hazard model was applied for analyzing the hazard ratio (HR) and 95% confidential interval (CI) for survival time of patients with pancreatic cancer. RESULTS: The levels of serum CA19-9, CEA, CA125 and CA242 in patients with pancreatic cancer were significantly higher than those in patients with benign pancreatic diseases and healthy people (P<0.001). The sensitivity of CA19-9 was the highest among these, followed by CA242, CA125 and CEA. The specificity of CA242 is the highest, followed by CA125, CEA and CA19-9. The sensitivity and specificity of joint detection of serum CA19-9, CEA, CA125and CA242 were 90.4% and 93.8%, obviously higher than single detection of those markers in diagnosis of pancreatic cancer. The median survival time of 52 patients with pancreatic cancer was 10 months (95% CI7.389~12.611).. Patients with the increasing level of serum CA19-9, CEA, CA125, CA242 had shorter survival times (P=0.047. 0.043, 0.0041, 0.029). COX regression analysis showed that CA19-9 was an independent prognostic factor for patients with pancreatic cancer (P=0.001, 95%CI 2.591~38.243). CONCLUSIONS: The detection of serum tumor markers (CA19.9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer and joint detection of tumor markers helps improve the diagnostic efficiency. Moreover, CA19-9 is an independent prognostic factor for patients with pancreatic cancer.