Effect of garlic component s-allyl cysteine sulfoxide on glycated human serum albumin induced activation of endothelial cells: an in vitro study.

OBJECTIVE: Alternative medicine or herbal therapies have been in use for blood glucose control in patients with diabetes for considerable time. Effect of garlic, more specifically its biologically active component s-allyl cysteine, on amelioration of hyperglycemia has also been reported. However, the cellular or molecular target of this compound is little known. This study was designed to determine the action of s-allyl cysteine sulfoxide (SACSO) at the cellular and molecular level in the widely reported HUVEC model when activated with advanced glycation end products (AGEs). MATERIALS AND METHODS: AGE-HSA was derived from non-enzymatic glycation of human serum albumin in the presence of 20 mM glucose. AGE-HSA induced expression of receptors of AGEs, namely RAGE and galectin-3 has been assayed. Activity of endothelial nitric oxide synthase (NOS) denoting normal endothelial function and expression of AGE-RAGE triggered inflammatory marker sICAM-1 is also evaluated in the presence or absence of SACSO. RESULTS: In presence of SACSO, AGE-HSA induced expression of RAGE was down-regulated, galectin-3 was significantly up-regulated, NOS activity was enhanced and sICAM-1 expression was reduced. CONCLUSIONS: The data suggest that SACSO exerts an attenuating effect on 20 mM glucose derived AGE-HSA induced inflammation, by selectively inhibiting RAGE while stimulating galectin-3 expression. The former triggers inflammatory pathways while the latter sequesters AGE molecules and prevents AGE-RAGE engagement. This may form the basis for its therapeutic action.

Outcomes of elderly patients aged 80 and over with symptomatic, severe aortic stenosis: impact of patient's choice of refusing aortic valve replacement on survival.

BACKGROUND: Aortic valve replacement (AVR) can be performed safely in selected elderly patients with aortic stenosis (AS). However, the survival benefits of AVR over conservative treatment have not been convincingly demonstrated in AS patients aged above 80. AIM: To investigate the outcomes of patients aged 80 and over with symptomatic, severe AS and by analyzing the effects of patient's choice in either agreeing or refusing to undergo AVR, determine the survival benefits afforded by AVR. DESIGN: Cohort study. METHODS: Subjects aged 80 and over with severe symptomatic AS, diagnosed between 2001 and 2006 were segregated into three groups: subjects who underwent AVR (Group A); patients who were fit for AVR but declined surgery due to personal choice (Group B) and those who were not fit for surgery and were managed conservatively (Group C). Follow-up was conducted by out-patient attendances, review of medical records and telephone interviews. The primary endpoint was all-cause mortality. RESULTS: A total of 103 patients (86.0 +/- 4.2 years, 41% male) were identified and no patient was lost during follow-up. In Group A (n = 17), all 15 patients who underwent AVR were alive after 3.6 +/- 1.4 years follow-up and 2 died whilst awaiting AVR. Seventy-four percent of Group B (n = 24) and 76% of Group C (n = 62) died during follow-up. Group A had significantly better survival than B and C. (P < 0.01) Amongst patients fit for AVR with similar operative risks (Groups A and B), refusal to undergo surgery (hazard ratio 12.61, P = 0.001) was the only predictor of mortality in a multivariate model. CONCLUSION: For elderly AS patients fit for surgery, the patient's decision to refuse AVR is associated with a >12-fold increase in mortality risk. These findings have significant implications for informed decision-making when managing the fit, elderly patient with AS.