ABSTRACT
BACKGROUND: Changes in the microbiota composition have been implicated in the development of obesity and type 2 diabetes. However, not much is known on the involvement of gut microbiota in lipid and cholesterol metabolism. In addition, the gut microbiota might also be a potential source of plasma oxyphytosterol and oxycholesterol concentrations (oxidation products of plant sterols and cholesterol). Therefore, the aim of this study was to modulate the gut microbiota by antibiotic therapy to investigate effects on parameters reflecting cholesterol metabolism and oxyphytosterol concentrations. DESIGN: A randomized, double blind, placebo-controlled trial was performed in which 55 obese, pre-diabetic men received oral amoxicillin (broad-spectrum antibiotic), vancomycin (antibiotic directed against Gram-positive bacteria) or placebo (microcrystalline cellulose) capsules for 7days (1500mg/day). Plasma lipid and lipoprotein, non-cholesterol sterol, bile acid and oxy(phyto)sterol concentrations were determined at baseline and after 1-week intervention. RESULTS: Plasma secondary bile acids correlated negatively with cholestanol (marker for cholesterol absorption, r=-0.367; P<0.05) and positively with lathosterol concentrations (marker for cholesterol synthesis, r=0.430; P<0.05). Fasting plasma secondary bile acid concentrations were reduced after vancomycin treatment as compared to placebo treatment (-0.24±0.22µmol/L vs. -0.08±0.29µmol/L; P<0.01). Vancomycin and amoxicillin treatment did not affect markers for cholesterol metabolism, plasma TAG, total cholesterol, LDL-C or HDL-C concentrations as compared to placebo. In addition, both antibiotic treatments did not affect individual isoforms or total plasma oxyphytosterol or oxycholesterol concentrations. CONCLUSION: Despite strong correlations between plasma bile acid concentrations and cholesterol metabolism (synthesis and absorption), amoxicillin and vancomycin treatment for 7days did not affect plasma lipid and lipoprotein, plasma non-cholesterol sterol and oxy(phyto)sterol concentrations in obese, pre-diabetic men.
Subject(s)
Amoxicillin/pharmacology , Anti-Bacterial Agents/pharmacology , Cholesterol/metabolism , Vancomycin/pharmacology , Administration, Oral , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Bile Acids and Salts/blood , Bile Acids and Salts/metabolism , Cholesterol/blood , Double-Blind Method , Humans , Male , Middle Aged , Obesity/blood , Obesity/metabolism , Prediabetic State/blood , Prediabetic State/metabolism , Vancomycin/administration & dosageABSTRACT
Since the introduction of radioiodinated m-iodobenzylguanidine in 1980, much research has been performed, both in the chemical field as well as in medical sciences. This paper reviews the synthesis, radiolabelling and stability of radioiodinated m-iodobenzylguanidine. Regarding the many radiolabelling procedures for m-iodobenzylguanidine, the Cu(1+)-assisted nucleophilic exchange radioiodination can be considered as the method of first choice. Quality control of the radiopharmaceutical product is discussed and attention is paid to recent studies regarding the radiochemical stability of iodine-131 labelled m-iodobenzylguanidine.
Subject(s)
Iodine Radioisotopes , Iodobenzenes/chemistry , Iodobenzenes/chemical synthesis , Sympatholytics/chemical synthesis , 3-Iodobenzylguanidine , Chromatography, High Pressure Liquid , Copper , Drug Stability , Indicators and Reagents , Isotope Labeling/methods , Sympatholytics/chemistryABSTRACT
An accurate and simple high-performance liquid chromatographic (HPLC) assay is presented for the quantitative determination of metaiodobenzylguanidine (MIBG) in human whole blood and plasma. The sample pretreatment involves a solid-phase extraction on Bakerbond SPE cyano columns. The HPLC system comprises a microBondapak C18 column and ammonium phosphate (pH4.0; 25 mM)-acetonitrile (80:20, v/v) as the mobile phase. Detection is performed by UV absorbance measurements at 254 nm. Linear regression with weighting factor l/chi 2 yielded the smallest sum of per cent relative concentration residuals over the concentration range of the assay (0.1-10 micrograms ml-1). MIBG levels, at the end of a 3-h infusion, in whole blood and plasma of carcinoid patients were measured and compared with the results obtained with radiodetection after addition of iodine-131-labelled MIBG.
