Combination anti-inflammatory therapy: synergism in rats of NSAIDs/corticosteroids with some herbal/animal products

A useful function of any complementary medicine is to supplement some of the benefits from other treatment modalities. In rats, extracts from Indian celery seed and the NZ green-lipped mussel are powerful nutraceuticals that (i) amplify the potency of salicylates and prednisone for treating pre-established chronic inflammation (arthritis, fibrosis) and (ii) reduce the steroid's gastrotoxic and lymphopenic side effects. Such combinations might also be useful for treating inflammatory components of (a) osteoarthritis caused by microcrystalline hydroxyapatite (BCP) and (b) pseudo-gout, associated with calcium pyrophosphate crystals; that are usually refractory to monotherapy.     

SEEDi: 动脉粥样硬化性心血管病一二级预防的基本策略

目前国内外对于动脉粥样硬化性心血管病(atherosclerotic cardiovascular disease,ASCVD)一二级的预防主 要基于药物和改善生活方式的ABCDE策略,或称“药物为主型策略”。作者2005年提出的由“四大健康要素”[睡 眠(sleep)、情绪(emotion)、运动(exercise)和饮食(diet)]构成的非药物且健康的“种子(SEED)”法则,或称SEED干预 (SEEDi)策略是指导慢性非传染性疾病,特别是指导ASCVD的一二级预防的基本策略。大力推广SEEDi策略,将使我 国ASCVD等慢性病的防治实现“三大转变”：由被动型向主动型转变、由如何治向如何防转变、由住院治疗向家庭 保健转变,从而形成我国ASCVD防治花费少、效果好的新局面,使ASCVD发病率和病死率明显下降,疾病预后和患 者生活质量显著改善。     

Specificity in the relationship between depressive and eating disorder symptoms in remitted and nonremitted women.

OBJECTIVE: There is a strong association between eating disorders and depression. However, because both eating disorder symptoms and depression are multifactorial, this study explored the relationship between these two disorders in women with eating disorders and women in remission. METHOD: Two hundred and eight (mostly female) volunteers with a history of eating disorders participated. They completed a self-report questionnaire of eating disorder symptoms, the Short Evaluation for Eating Disorders (SEED), and a questionnaire measuring depression, the Beck Depression Inventory (BDI). RESULTS: According to the SEED, 57 volunteers were classified as being in remission and 151 were classified as being ill. Those who were in remission were significantly less depressed overall than those who were still ill with 72% of the former falling in the "not depressed" or "mildly depressed" categories and 73% of the latter falling in the "moderately" or "severely depressed" categories. Factor analyses of the SEED and BDI identified three subscales of eating disorder symptoms (dietary restriction, bulimia, and body mass index [BMI]/menstruation) and two subscales of depression (cognitive and somatic/affective). Dietary restriction and bulimia, but not BMI/menstruation, were uniquely associated with the cognitive symptoms of depression. However, none of the eating disorder symptoms were uniquely associated with the somatic/affective symptoms of depression. DISCUSSION: Although eating disorders and depression share considerable comorbidity, a specific association is restricted to that between the cognitive and behavioral symptoms of eating disorders and the cognitive symptoms of depression.     

Hydrophobicity maps and docking of molecular fragments with solvation

Two methods for structure-based computational ligand design are reviewed. Hydrophobicity maps allow to quantitatively estimate and graphically display the propensity of nonpolar groups to bind at the surface of a protein target [Scarsi etal., Proteins Struct. Funct. Genet., 37 (1999) 565].The program SEED (Solvation Energy for Exhaustive Docking) finds optimal positions and orientations of nonpolar fragments using the hydrophobicity maps, while polar fragments are docked with at least one hydrogen bond with the protein [Majeuxet al., Proteins Struct. Funct. Genet., 37 (1999) 88]. An efficient evaluation of the binding energy, including continuum electrostatic solvation, allows to dock a library of 100 fragments into a 25-residue binding site in about five hours on a personal computer. Applications to thrombin, a key enzyme in the blood coagulation cascade, andthe p38 mitogen-activated protein kinase, which is a target for the treatment of inflammatory and neurodegenerative diseases, are presented. The role of the hydrophobicity maps and structure-based docking of a fragment library in exploiting genomes to design drugs is addressed. This revised version was published online in June 2006 with corrections to the Cover Date.     

NSAID gastropathy: prevention by celery seed extracts in disease-stressed rats

Previous studies showed that some anti-inflammatory celery seed extracts (CSEs) were not gastrotoxic, in contrast to many OTC NSAIDs, when dosed to arthritic rats. The present investigation was designed to quantify the potential activity of CSEs against NSAID injury in rats with severe acute or chronic inflammation and to define the possible relationship of this to effects on mucosal prostaglandin production. Oral doses of alcoholic (A-CSE) (150-300 mg/kg) and supercritical fluid (S-CSE)(20-50 mg/kg) extracts of seeds of wild celery Apium graveolens from north India (Beagle Int. Nerang, Qld.) profoundly suppressed gastric injury elicited in disease-stressed female rats (Wistar, DA) with (a) chronic arthritic inflammation or (b) severe acute inflammation (from oleyl alcohol, 0.1 ml in tail base), fasted overnight and then dosed either (i) orally with ibuprofen (50 mg/kg), sodium naproxen (27.5 mg/kg), ketoprofen (5 mg/kg) or acidic ethanol (150 mg/kg); or (ii) parenterally with piroxicam (5 mg/kg) or nabumetone (100 mg/kg). By contrast several conventional gastroprotectants, e.g. sucralfate, cimetidine, bismuth salts, all given orally were ineffective in preventing gastric injury from parenteral piroxicam. Gastroprotection by CSEs was not over-ridden by co-dosing with isotonic HCl. Most other celery seed 'oils' were ineffective in these assays. A-CSE was found to have marked inhibitory effects on PGE₂ production by porcine gastric (fundic) mucosal explants in organ culture. Quercetin and mycrecetin which are reported components of some CSEs also inhibited PGE₂ production in concentrations of 10 _M, whereas limonene, another reported component of CSEs had little effect at the same concentration. These results suggest that gastroprotective effects of CSEs are probably mediated through non-prostaglandin mechanisms.