Physico-chemical characterization and pharmacological evaluation of sulfated polysaccharides from three species of Mediterranean brown algae of the genus Cystoseira

Background

Seaweed polysaccharides are highly active natural substances having valuable applications. The present study was conducted to characterize the physico-chemical properties of sulphated polysaccharides from three Mediterranean brown seaweeds (Cystoseira sedoides, Cystoseira compressa and Cystoseira crinita) and to evaluate their anti-radical, anti-inflammatory and gastroprotective activities.

Methods

The different rates of neutral sugars, uronic acids, L-fucose and sulphate content were determined by colorimetric techniques. The different macromolecular characteristics of isolated fucoidans were identified by size exclusion chromatography equipped with a triple detection: multiangle light scattering, viscometer and differential refractive index detectors, (SEC/MALS/VD/DRI). Anti-inflammatory activity was evaluated, using the carrageenan-induced rat paw edema test in comparison to the references drugs Acetylsalicylate of Lysine and Diclofenac. The gastroprotective activity was determined using HCl/EtOH induced gastric ulcers in rats and to examine the antioxidant effect of fucoidans in the three species, the free radical scavenging activity was determined using 1,1-diphenyl-2-picrylhydrazyl.

Results

The pharmacological evaluation of the isolated fucoidans for their anti-inflammatory, and their gastroprotective effect established that these products from C. sedoides, C. compressa and C. crinita exhibited a significant anti-inflammatory activity at a dose of 50 mg/kg, i.p; the percentages of inhibition of the oedema were 51%, 57% and 58% respectively. And, at the same dose, these fucoidans from C. sedoides and C. compressa showed a significant decrease of the intensity of gastric mucosal damages compared to a control group by 68%, whereas, the fucoidan from C. crinita produced a less gastroprotective effect. Furthermore, the isolated fucoidans exhibited a radical scavenging activity.

Conclusion

The comparative study of fucoidans isolated from three species of the genus Cystoseira showed that they have similar chemicals properties and relatives anti-radical, anti-inflammatory and gastroprotective activities which are found to be promising.     

Brucella endocardititis: clinical particularities and therapeutic modalities

Brucella infective endocarditis is an uncommon, but serious complication of brucellosis. The aortic valve is the most commonly affected cardiac valve. Due to characteristics of the infection, medical therapy alone is not sufficient in treating the disease and best results are obtained with surgery combination. We describe a case of Brucella endocarditis involving the aortic valve suspected in front of the clinical data and the results of serology, confirmed by the culture of the native valves. In association with the medical treatment, management valve replacement lead to a favorable medium-term evolution.     

The Role of Cyclooxygenase-2 in Inflammation

Prostaglandins (PGs) can be synthetized via two isoforms of cyclooxygenase (COX). COX-1 is constitutively expressed in normal tissues, and its activity represent the normal physiological output of PGs. In inflammatory states, the newly discovered COX-2 is rapidly induced, and its activity accounts for the large amounts of PGs seen in inflammation. The commercially available nonsteroidal anti-inflammatory drugs (NSAIDs) are nonselective inhibitors of both COX isoforms; therefore, they provide anti-inflammatory activity as well as side effects associated with COX-1 inhibition. Selective inhibition of COX-2 expression explains at least in part the potent anti-inflammatory activity of steroids. Anti-inflammatory activity of newly developed COX-2 inhibitors, such as NS-398 or SC-58125, suggest a new approach of inflammatory diseases with more efficacious NSAIDs essentially devoid of side effects such as stomach ulcers.     

Comparative in vitro and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A by H2-receptor antagonists

The isozymes CYP1A2, CYP2D6, and CYP3A4/5 are involved in the majority of all cytochrome P450-mediated drug biotransformations. In this study we investigated the inhibition profiles of CYP1A2 (substrate: caffeine) CYP2D6 (substrate: dextromethorphan), and CYP3A4/5 (substrate: dextrorphan) by cimetidine, ranitidine, and the novel H2-receptor antagonist ebrotidine in human liver microsomes. The inhibitory effect of the drugs on the enzymes activities were as follows: CYP1A2: cimetidine > ranitidine = ebrotidine; CYP2D6: cimetidine > ranitidine = ebrotidine; CYP3A4/5: ebrotidine > cimetidine > ranitidine. The inhibition of CYP3A4/5 enzyme activity by ebrotidine was competitive. To test whether the inhibitory effect of ebrotidine in CYP3A activity was also found in vivo, we analyzed the biodisposition of midazolam in 8 healthy volunteers. Midazolam biodisposition was significantly reduced when administered together with cimetidine (P < .05), whereas no significant inhibition was observed with ebrotidine or ranitidine compared with placebo. Psychomotor performance analysis revealed no significant effect of the observed reduction on midazolam biodisposition. We concluded that patients who are receiving treatment with drugs metabolized through CYP3A may experience enhanced drug effects as a result of pharmacokinetic interaction when treated concomitantly with cimetidine. In contrast, the effect of ranitidine or ebrotidine on CYP3A activity in vivo seems to have little clinical significance.     

Pathomechanics of the throwing shoulder

Many anatomic, physiological, and biomechanical alterations have been observed in overhead athletes who present with painful shoulders. This is probably due to the complex kinetic chain mechanics required in the overhead throwing or serving motion. Any alteration along the kinetic chain can result in deficits in force production or increase in joint loads in other parts of the chain. The "disabled throwing shoulder" (DTS) is a general term that describes the limitations in function that exist in symptomatic overhead athletes. DTS typically results from a "cascade to injury" with alterations in the kinetic chain. Evaluation of athletes with the DTS should include examination of the local and distant anatomic injuries and screening for physiological (muscle inflexibilities, weakness, or imbalances) or biomechanical (motions, positions) alterations.     

Internal impingement: concurrent superior labral and rotator cuff injuries

Internal impingement is a general term usually applied to the pathologic combination of a superior labral anterior-posterior injury and a partial thickness rotator cuff injury that is commonly seen in the disabled throwing shoulder. Clinical presentation varies but involves a combination of internal derangement (popping, clicking, catching, sliding) and rotator cuff weakness. Evaluation should be precise to delineate all components of the injury. Treatment must be directed toward both of the components and any other coexisting pathology. Labral repair should aim at restoring all aspects of the roles of the labrum. Rotator cuff treatment should take into account the need for optimal rotation and may not include complete take down and repair. Pitfalls in diagnosing and treating internal impingement should be known and avoided. Comprehensive rehabilitation emphasizing kinetic chain principles and full ranges of motion should be used.     

Improving integrated team working to support people to die in the place of their choice

Dying in a place of one's choice is considered to be a quantifiable measure of the effectiveness of end of life services in primary care. Although most people say they would prefer to die in their own home, very few actually do so. This article looks at how a team of community nurses and GPs changed their practice by using recognised end of life care tools. These helped practitioners in supporting adults with terminal illnesses to die in a place of their choice. A subsequent audit of patients' actual place of death against their preferred place demonstrates how working in more integrated ways has helped.