Alkylation of 6-thiopurine derivatives by the Mitsunobu reaction

Alkylation of thiopurine derivatives with alcohols by the Mitsunobu reaction are reported in moderated to good yields. The method was applied in synthesis of number of thiopurine and thiopurine ribosides derivatives.</p

Advanced glycation end products dietary restriction effects on bacterial gut microbiota in peritoneal dialysis patients; a randomized open label controlled trial

<div><p>The modern Western diet is rich in advanced glycation end products (AGEs). We have previously shown an association between dietary AGEs and markers of inflammation and oxidative stress in a population of end stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). In the current pilot study we explored the effects of dietary AGEs on the gut bacterial microbiota composition in similar patients. AGEs play an important role in the development and progression of cardiovascular (CVD) disease. Plasma concentrations of different bacterial products have been shown to predict the risk of incident major adverse CVD events independently of traditional CVD risk factors, and experimental animal models indicates a possible role AGEs might have on the gut microbiota population. In this pilot randomized open label controlled trial, twenty PD patients habitually consuming a high AGE diet were recruited and randomized into either continuing the same diet (HAGE, <i>n</i> = 10) or a one-month dietary AGE restriction (LAGE, <i>n</i> = 10). Blood and stool samples were collected at baseline and after intervention. Variable regions V3-V4 of 16s rDNA were sequenced and taxa was identified on the phyla, genus, and species levels. Dietary AGE restriction resulted in a significant decrease in serum N^<i>ε</i>-(carboxymethyl) lysine (CML) and methylglyoxal-derivatives (MG). At baseline, our total cohort exhibited a lower relative abundance of <i>Bacteroides</i> and <i>Alistipes</i> genus and a higher abundance of <i>Prevotella</i> genus when compared to the published data of healthy population. Dietary AGE restriction altered the bacterial gut microbiota with a significant reduction in <i>Prevotella copri</i> and <i>Bifidobacterium animalis</i> relative abundance and increased <i>Alistipes indistinctus</i>, <i>Clostridium citroniae</i>, <i>Clostridium hathewayi</i>, and <i>Ruminococcus gauvreauii</i> relative abundance. We show in this pilot study significant microbiota differences in peritoneal dialysis patients’ population, as well as the effects of dietary AGEs on gut microbiota, which might play a role in the increased cardiovascular events in this population and warrants further studies.</p></div

One month dAGE restriction resulted in changes in gut bacterial microbiota.

<p>Operational taxonomic units were annotated and analyzed at species levels, and shows no difference in microbiota projection onto the principal components at baseline (A), followed by changes after dietary intervention (B). HAGE, high advanced glycation end products group; LAGE, low advanced glycation end products group.</p

Species (A), genus (B), and Phyla (C) differences between groups at baseline and after intervention.

<p>HAGE (bl), high advanced glycation end products group at baseline; LAGE (bl), low advanced glycation end products group at baseline; HAGE (Int), high advanced glycation end products group after intervention; LAGE (Int), low advanced glycation end products group after intervention. The top ten species in relative abundance (74%) are shown in Fig 3A, full species are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0184789#pone.0184789.s002" target="_blank">S2 Fig</a>.</p

Shannon-Wiener diversity index indicating no differences among groups before and after intervention (bars and columns represent diversity index mean ± standard deviation).

<p>HAGE (bl), high advanced glycation end products group at baseline; LAGE (bl), low advanced glycation end products group at baseline; HAGE (Int), high advanced glycation end products group after intervention; LAGE (Int), low advanced glycation end products group after intervention.</p