Advanced oxidation protein products (AOPPs) in juvenile overweight and obesity prior to and following weight reduction

Objectives

To evaluate the formation of advanced oxidation protein products (AOPPs) in juvenile overweight/obesity and obesity-related disorders and to investigate the effect of weight reduction on AOPPs.

Design and methods

AOPPs were determined in 114 overweight/obese children and adolescents without/with insulin resistance and metabolic syndrome and compared with 53 lean controls. Measurements were repeated following weight reduction program (diet/exercise, bran-enriched diet/exercise, and diet/exercise plus metformin).

Results

Overweight/obese subjects had higher AOPPs than lean controls, more elevated in patients with co-occurring metabolic syndrome. AOPPs positively correlated with central obesity, triglycerides, lipid peroxidation and insulin, and negatively with glucose to insulin ratio. AOPPs decreased following obesity intervention and ΔAOPPs correlated with ΔBMI%. AOPPs reduction was more pronounced in subjects on bran-enriched diet. Baseline AOPPs were a better predictor of clinically significant weight reduction than BMI%.

Conclusions

Juvenile overweight/obesity was associated with AOPPs accumulation, more pronounced in metabolic syndrome. Body mass reduction decreased oxidative stress, with bran-enriched diet being more effective than diet/exercise alone.     

Terminalia arjuna Wight & Arn.--a useful drug for cardiovascular disorders

Ancient Indian physicians used the powdered tree bark of Terminalia arjuna Wight & Arn. for alleviating "hritshool" (angina) and other cardiovascular conditions. Its stem bark possesses glycosides, large quantities of flavonoids, tannins and minerals. Flavonoids have been detected to exert antioxidant, anti-inflammatory and lipid lowering effects while glycosides are cardiotonic, thus making Terminalia arjuna unique amongst currently used medicinal plants. In this review an attempt has been made to discuss various aspects of its ethnomedical, pharmacognostical, phytochemical, pharmacological and clinical relevance to cardiovascular conditions. Experimental studies have revealed its bark exerting significant inotropic and hypotensive effect, increasing coronary artery flow and protecting myocardium against ischemic damage. It has also been detected to have mild diuretic, antithrombotic, prostaglandin E(2) enhancing and hypolipidaemic activity. There is ample clinical evidence of its beneficial effect in coronary artery disease alone and along with statin. However, toxicological studies in experimental animals are lacking. Considering its anti-ischemic activity and its potential to correct dyslipidemia, reduce left ventricular mass and increase left ventricular ejection fraction, it is essential to examine the molecular mechanism of its action and its core constituents. Proposition to administer Terminalia arjuna along with statins deserves to be explored in depth for defining its place in the over all management and prevention of coronary artery disease.     

Managing cardiovascular disease risk in South Asian kidney transplant recipients

South Asians (SA) are at higher cardiovascular risk than other ethnic groups, and SA kidney transplant recipients (SA KTR) are no exception. SA KTR experience increased major adverse cardiovascular events both early and late post-transplantation. Cardiovascular risk management should therefore begin well before transplantation. SA candidates may require aggressive screening for pre-transplant cardiovascular disease (CVD) due to their ethnicity and comorbidities. Recording SA ethnicity during the pre-transplant evaluation may enable programs to better assess cardiovascular risk, thus allowing for earlier targeted peri- and post-transplant intervention to improve cardiovascular outcomes. Diabetes remains the most prominent post-transplant cardiovascular risk factor in SA KTR. Diabetes also clusters with other metabolic syndrome components including lower high-density lipoprotein cholesterol, higher triglycerides, hypertension, and central obesity in this population. Dyslipidemia, metabolic syndrome, and obesity are all significant CVD risk factors in SA KTR, and contribute to increased insulin resistance. Novel biomarkers such as adiponectin, apolipoprotein B, and lipoprotein (a) may be especially important to study in SA KTR. Focused interventions to improve health behaviors involving diet and exercise may especially benefit SA KTR. However, there are few interventional clinical trials specific to the SA population, and none are specific to SA KTR. In all cases, understanding the nuances of managing SA KTR as a distinct post-transplant group, while still screening for and managing each CVD risk factor individually in all patients may help improve the long-term success of all kidney transplant programs catering to multi-ethnic populations.     

Progressively decreasing plasma high-density lipoprotein cholesterol levels preceding diagnosis of smoldering myeloma

We report a case of disappearing high-density lipoprotein (HDL) syndrome caused by oxidative modification of HDL and by autoantibodies against modified HDL, with subsequent diagnosis of myeloma. An elderly Caucasian man had normal lipid levels with HDL cholesterol (HDL-C) levels in the upper 70 mg/dL range from 1999 to 2003. In 2003, his HDL-C levels began to progressively fall, and by 2011, they were undetectable (<5 mg/dL) when measured with a Beckman Synchron LX auto analyzer. Analyses of the plasma sample from 2011 using ultracentrifugation (Vertical Auto Profile), nuclear magnetic resonance, and Ace EXCEL auto analyzer have shown that HDL-C levels were easily detectable (47–54 mg/dL), although reduced compared with his pre-2003 values. Analyses of his plasma sample from 2011 also showed the presence of lipid-adducted apolipoprotein A1 (apoA1) and high titer of antibodies against the adducted apoA1. Interestingly, a negative correlation between HDL-C levels and the titer of antibodies against apoA1 adducts was found in the control cohort. Finally, we show that in the mouse system, an antibody against apoA1 increases the clearance of HDL from plasma. This case of smoldering myeloma preceded by acquired, severe HDL-C deficiency, likely because of oxidative modifications of the HDL protein leading to the formation of autoantibodies, interference with clinical measurement of HDL-C, and increased plasma clearance of HDL, adds to the list of diagnostic considerations for unexplained HDL-C decreases over time.