6-Shogaol reduced chronic inflammatory response in the knees of rats treated with complete Freund's adjuvant

BACKGROUND: 6-Shogaol is one of the major compounds in the ginger rhizome that may contribute to its anti-inflammatory properties. Confirmation of this contribution was sought in this study in Sprague- Dawley rats (200–250 g) treated with a single injection (0.5 ml of 1 mg/ml) of a commercial preparation of complete Freund's Adjuvant (CFA) to induce monoarthritis in the right knee over a period of 28 days. During this development of arthritis, each rat received a daily oral dose of either peanut oil (0.2 ml-control) or 6-shogaol (6.2 mg/Kg in 0.2 ml peanut oil). RESULTS: Within 2 days of CFA injection, the control group produced maximum edematous swelling of the knee that was sustained up to the end of the investigation period. But, in the 6-shogaol treated group, significantly lower magnitudes of unsustained swelling of the knees (from 5.1 ± 0.2 mm to 1.0 ± 0.2 mm, p < 0.002, n = 6) were produced during the investigation period. Unsustained swelling of the knees (from 3.2 ± 0.6 mm to 0.8 ± 1.1 mm, p < 0.00008, n = 6) was also produced after 3 days of treatment with indomethacin (2 mg/Kg/day) as a standard anti-inflammatory drug, but during the first 2 days of drug treatment swelling of the knees was significantly larger (11.6 ± 2.0 mm, p < 0.0002, n = 6) than either the controls or the 6-shogaol treated group of rats. This exaggerated effect in the early stage of indomethacin treatment was inhibited by montelukast, a cysteinyl leukotriene receptor antagonist. Also, 6-shogaol and indomethacin were most effective in reducing swelling of the knees on day 28 when the controls still had maximum swelling. The effect of 6-shogaol compared to the controls was associated with significantly lower concentration of soluble vascular cell adhesion molecule-1 (VCAM-1) in the blood and infiltration of leukocytes, including lymphocytes and monocytes/macrophages, into the synovial cavity of the knee. There was also preservation of the morphological integrity of the cartilage lining the femur compared to damage to this tissue in the peanut oil treated control group of rats. CONCLUSION: From these results, it is concluded that 6-shogaol reduced the inflammatory response and protected the femoral cartilage from damage produced in a CFA monoarthritic model of the knee joint of rats

Determinants of leptospirosis in Sri Lanka: Study Protocol

<p>Abstract</p> <p>Background</p> <p>Leptospirosis is becoming a major public health threat in Sri Lanka as well as in other countries. We designed a case control study to determine the factors associated with local transmission of leptospirosis in Sri Lanka, in order to identify major modifiable determinants of leptospirosis. The purpose of this paper is to describe the study protocol in detail prior to the publishing of the study results, so that the readership will be able to understand and interpret the study results effectively.</p> <p>Methods</p> <p>A hospital based partially matched case control design is proposed. The study will be conducted in three selected leptospirosis endemic districts in central Sri Lanka. Case selection will include screening all acute fever patients admitted to selected wards to select probable cases of leptospirosis and case confirmation using an array of standard laboratory criteria. Age and sex matched group of acute fever patients with other confirmed diagnosis will be used as controls. Case to control ratio will be 1:2. A minimum sample of 144 cases is required to detect 20% exposure with 95% two sided confidence level and 80% power. A pre tested interviewer administered structured questionnaire will be used to collect data from participants. Variables included in the proposed study will be evaluated using conceptual hierarch of variables in three levels; Exposure variables as proximal; reservoir and environmental variables as intermediate; socio-demographic variables as distal. This conceptual hierarch hypothesised that the distal and intermediate variables are mediated through the proximal variables but not directly. A logistic regression model will be used to analyse the probable determinants of leptospirosis. This model will evaluate the effect of same level and upper level variables on the outcome leptospirosis, using three blocks.</p> <p>Discussion</p> <p>The present national control programme of leptospirosis is hampered by lack of baseline data on leptospirosis disease transmission. The present study will be able to provide these essential information for formulation of better control strategies.</p