Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model.

OBJECTIVE: Using a thrombus model prepared by ligation of the inferior vena cava (IVC), the influences of the glycoside, glycyrrhizin, on plasma antithrombin levels and antithrombin mRNA expression levels in the liver and IVC with the inhibition of venous thrombosis were investigated. MATERIALS AND METHODS: The rat IVC was exposed and ligated for 24 h immediately after the intravenous administration of 300 mg/kg glycyrrhizin. Among antithrombotic drugs, the Xa inhibitor, fondaparinux sodium, was used as a control drug. RESULTS: The mean thrombus weight was significantly smaller in the glycyrrhizin-treated group (18.3 mg) than in the saline-treated group (34.3 mg). In contrast, the inhibition of thrombosis was not observed in the fondaparinux-treated group. Antithrombin mRNA expression levels in the liver were significantly higher in the ligated groups than in the baseline control group. The mean plasma antithrombin level was significantly lower in the glycyrrhizin group (96.6%) than in the saline group (114.4%), but was not significantly different from that in the baseline control group (102.4%). CONCLUSION: The pretreatment with glycyrrhizin inhibited venous thrombosis, and antithrombin mRNA expression levels in the liver and IVC as well as plasma antithrombin levels were significantly lower than those in the saline group.

Tuberculosis infection among homeless persons and caregivers in a high-tuberculosis-prevalence area in Japan: a cross-sectional study.

BACKGROUND: Tuberculosis (TB) is a major public health problem. The Airin district of Osaka City has a large population of homeless persons and caregivers and is estimated to be the largest TB-endemic area in the intermediate-prevalence country, Japan. However, there have been few studies of homeless persons and caregivers. The objective of this study is to detect active TB and to assess the prevalence and risk factors for latent TB infection among homeless persons and caregivers. METHODS: We conducted a cross-sectional study for screening TB infection (active and latent TB infections) using questionnaire, chest X-ray (CXR), newly available assay for latent TB infection (QuantiFERON-TB Gold In-Tube; QFT) and clinical evaluation by physicians at the Osaka Socio-Medical Center Hospital between July 2007 and March 2008. Homeless persons and caregivers, aged 30-74 years old, who had not received CXR examination within one year, were recruited. As for risk factors of latent TB infection, the odds ratios (OR) and 95% confidence intervals (95% CI) for QFT-positivity were calculated using logistic regression model. RESULTS: Complete responses were available from 436 individuals (263 homeless persons and 173 caregivers). Four active TB cases (1.5%) among homeless persons were found, while there were no cases among caregivers. Out of these four, three had positive QFT results. One hundred and thirty-three (50.6%) homeless persons and 42 (24.3%) caregivers had positive QFT results. In multivariate analysis, QFT-positivity was independently associated with a long time spent in the Airin district: ≥10 years versus <10 years for homeless (OR = 2.53; 95% CI, 1.39-4.61) and for caregivers (OR = 2.32; 95% CI, 1.05-5.13), and the past exposure to TB patients for caregivers (OR = 3.21; 95% CI, 1.30-7.91) but not for homeless persons (OR = 1.51; 95% CI, 0.71-3.21). CONCLUSIONS: Although no active TB was found for caregivers, one-quarter of them had latent TB infection. In addition to homeless persons, caregivers need examinations for latent TB infection as well as active TB and careful follow-up, especially when they have spent a long time in a TB-endemic area and/or have been exposed to TB patients.

Prevention of venous thrombosis by preoperative glycyrrhizin infusion in a rat model.

BACKGROUND: Glycyrrhizin is an agent with the capacity to bind to selectin molecules expressed on vascular endothelial cells and potentially prevent the adherence of neutrophils to the vascular endothelial surface. It has been found to prevent intravenous thrombus formation. METHODS: Venous thrombosis was induced in male rats by ligation of the inferior vena cava (IVC) for 6 h. Before the ligation, the study rats were given intravenous injections of glycyrrhizin through the IVC. After 6 h of venous ligation, the rats were sacrificed and the IVC segments were harvested. Thrombus within the IVC was collected to measure the wet weight. Gene expression of P-, L-, and E-selectin was detected by reverse transcriptase polymerase chain reaction using extracts of mRNA from the IVC vein wall. As baseline controls, IVC samples without ligation were harvested immediately after laparotomy. Neutrophil adhesion to the luminal surface of IVC was assessed on histological sections stained with hematoxylin and eosin. Blood samples were collected through the IVC proximal to the ligation after 6 h to estimate activated partial thromboplastin time (APTT) and prothrombin time (PT). To investigate the effect of glycyrrhizin on binding capacity of P-selectin to human neutrophils, real-time biospecific interaction analysis was performed with the Biacore 2000 system. RESULTS: The mean weight of thrombus in the glycyrrhizintreated group was 12.9 +/- 11.1 mg, which is significantly lower than that of the saline-treated control group (21.3 +/- 12.5 mg). The expression level of P-and L-selectin mRNA in both saline-and glycyrrhizin-treated groups was significantly higher than that of the baseline control. Histological studies of cross sections of IVC showed significantly fewer neutrophils adhering to the luminal surface with glycyrrhizin treatment than in the saline-treated controls. There was no significant difference in the values of coagulation parameters with or without glycyrrhizin treatment. In vitro analysis showed that glycyrrhizin caused a dose-dependent reduction of neutrophils binding to immobilized recombinant P-selectin. CONCLUSIONS: Preoperative treatment with glycyrrhizin is potentially useful for preventing venous thrombosis by suppressing the adherence of neutrophils to the venous endothelium during the initial phase of thrombus formation without reducing coagulation capacity and the subsequent risk for increased bleeding.

[Significance of tuberculosis screening of outpatients in areas with high prevalence of tuberculosis].

OBJECTIVE: The Osaka Socio-Medical Center Hospital is a medical care facility located in the Airin area of Osaka city where the prevalence of tuberculosis is high, and treats day laborers and homeless people mainly, either free of charge or with a small fee. To investigate whether this hospital can play a role to reduce the prevalence of tuberculosis in this area, we investigated the case rate of active tuberculosis in outpatients of the hospital. SUBJECTS AND METHODS: Of 1673 patients who first visited the Orthopaedic Outpatient Clinic between March 31, 2005 and June 15, 2006, 538 patients consented to undergo screening and underwent chest X-ray examination (screening group). We also analyzed chest X-ray examination in 2000 patients examined at the Department of Internal Medicine during the same period (control group). RESULTS: Of the 538 patients in the screening group (523 males and 15 females), 13 male patients (2.4%) requiring treatment were detected. Of the 2000 patients in the control group, 85 patients (84 males and 1 female) (4.3%) requiring treatment were detected. CONCLUSION: The tuberculosis case rate (2.4%) in the screening group was similar to that of tuberculosis screenings (1.1-1.8%) in the Airin area in 2004. The case rate in the control group was two times higher. Since the prevalence is very high in patients of this hospital, the hospital should play a significant role in the health care of tuberculosis patients in this community by reinforcing the screening system and enriching the outpatient clinic system.

Use of glycyrrhizin in prevention of tissue damage caused by ischemia-reperfusion in rabbit hind limbs.

BACKGROUND: Glycyrrhizin, an agent that can bind to selectins and inhibit their ability to bind neutrophils, was found to be effective in preventing tissue edema caused by ischemia-reperfusion in a rabbit model. METHODS: Complete ischemia was produced by applying a tight Esmarch tourniquet to the hind limbs of 24 Japanese white rabbits. Immediately before and 1 h after release of the tourniquet, 12 animals were given glycyrrhizin intravenously; 12 controls received saline. RESULTS: The mean relative increase in the circumference of the shins before and after ischemia-reperfusion with or without glycyrrhizin treatment was 4.6% +/- 2.4% and 9.6% +/- 4.2%, respectively, indicating that tissue edema caused by the ischemia-reperfusion was significantly attenuated by glycyrrhizin. Histological studies of cross sections of the anterior tibial muscle 24 h after reperfusion showed a significant reduction in the incidence of necrotic muscle fibers in the glycyrrhizin-treated animals compared with the controls that did not receive glycyrrhizin. The mRNA levels of P- and E-selectin 24 h after reperfusion were significantly higher in the ischemic anterior tibial muscle than in the nonischemic normal muscle. After 24 h of reperfusion, the mean activity of myeloperoxidase, a neutrophil-specific enzyme, in the anterior tibial muscles of the group given glycyrrhizin (0.0022 +/- 0.0013 absorbance units) was lower than that of the untreated group (0.027 +/- 0.026 absorbance units). CONCLUSIONS: These data suggest that glycyrrhizin treatment is effective in suppressing the acute inflammatory reaction or edema following ischemia-reperfusion and might be potentially useful in clinical practice for preventing ischemia-reperfusion injuries to the extremities.