OBJECTIVETo study the modulation effect of pro- and anti-inflammatory cytokines following long term use of water soluble ethanol extracts from different organs of Nyctanthes arbortristis (NAT) in mouse model of arthritis.

METHODSArthritis was induced in mice by two injections of Freund's complete adjuvant on days 0 and 12 in the sub-planter surface of the right hind paw.

RESULTSInjection of adjuvant resulted in a maximum primary edema of the footpad with erythema, and edema and distortion of joints of the right hind paw after 24-48 hours. Second injection of FCA led to the formation of secondary swellings persisting more than four weeks that spread onto the other hind limb but to a lesser extent. Histological analysis of the ankle on day 47 showed marked evidence of cartilage destruction in association with pannus formation and moderate bone resorption. Proinflammatory cytokine levels in the inflamed joint homogenate were elevated on days 2, 14, and 47. Oral administration of leaf and fruit extracts in arthritic mice reduced joint homogenate levels of tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 on days 2, 14, and 47 in comparison to untreated arthritic mice. Interleukin-10 level was elevated in the inflamed joint on days 2, 14, and 47 in comparisons to untreated arthritic mice.

CONCLUSIONEvidence of lesser inflammation of the footpad and joint and associated histological observation support the therapeutic benefit of leaf and fruit extracts from Nyctanthes arbortristis. This study helps in understanding the mechanism of anti-inflammatory action of Nyctanthes arbortristis in the light of pro- and anti-inflammatory cytokine balance.

Animals ; Arthritis, Experimental ; drug therapy ; immunology ; pathology ; Cytokines ; metabolism ; Disease Models, Animal ; Female ; Mice ; Mice, Inbred BALB C ; Oleaceae ; chemistry ; Phytotherapy ; Plant Extracts ; isolation & purification ; therapeutic use

INTRODUCTIONWe aimed to assess the efficacy of fixed dose combination of atorvastatin plus ezetimibe in Indian patients with dyslipidaemia.

METHODSA double-blind study was conducted to assess the effect of fixed dose combination of ezetimibe 10 mg plus atorvastatin 10 mg on lipid profile, oxidised low-density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hsCRP) and soluble intercellular cell adhesion molecule (sICAM) in dyslipidaemic patients with or at high risk of coronary artery disease, and compare it with atorvastatin 10 mg monotherapy. 30 patients were randomised to receive ezetimibe plus atorvastatin or atorvastatin once daily for four weeks.

RESULTSOf the 30 patients, 10 men and 5 women (mean age 54.3 ± 1.6 years) received ezetimibe plus atorvastatin, while 13 men and 2 women (mean age 53.7 ± 2.8 years) received only atorvastatin. The combination treatment significantly reduced total cholesterol (percentage treatment difference -14.4 ± 6.5, 95% confidence interval [CI] -1.0 to -27.7; p = 0.041) and LDL cholesterol (LDL-C; percentage treatment difference -19.9 ± 6.1, 95% CI -7.4 to -32.4; p = 0.003) compared to atorvastatin monotherapy. 13 patients on combination treament achieved the National Cholesterol Education Program target for LDL-C as compared to 9 patients on atorvastatin monotherapy (p = 0.032). Significant reductions in very low-density lipoprotein cholesterol, triglyceride, ox-LDL and sICAM were observed with combination treatment compared to atorvastatin monotherapy. However, no significant change was seen in high-density lipoprotein cholesterol or hsCRP levels between the two groups.

CONCLUSIONCombination treatment with atorvastatin and ezetimibe had relatively better lipid-lowering and anti-inflammatory efficacy than atorvastatin monotherapy.

Anti-Inflammatory Agents ; therapeutic use ; Anticholesteremic Agents ; administration & dosage ; Atorvastatin Calcium ; Azetidines ; administration & dosage ; C-Reactive Protein ; metabolism ; Double-Blind Method ; Drug Therapy, Combination ; methods ; Dyslipidemias ; drug therapy ; Ezetimibe ; Female ; Heptanoic Acids ; administration & dosage ; Humans ; Hypolipidemic Agents ; therapeutic use ; India ; Intercellular Adhesion Molecule-1 ; metabolism ; Lipoproteins, LDL ; metabolism ; Male ; Middle Aged ; Pyrroles ; administration & dosage ; Treatment Outcome