Resolution of acute gastroenteritis symptoms in children and adults treated with a novel polyphenol-based prebiotic.

AIM: To test efficacy and durability of a polyphenol-based prebiotic treatment for acute gastroenteritis in a 300 patient double-blinded clinical study. METHODS: A two-arm randomized, double-blinded, placebo-controlled clinical study was conducted at two public health centers in Managua, Nicaragua. Potential subjects who qualified based on inclusion and exclusion criteria were randomly assigned to one of two treatment arms. Two thirds of the subjects (n = 200) received a single titrated 0.5-2 ounce liquid dose of a novel polyphenol-based prebiotic (Aliva(TM)) diluted with 2 to eight ounces of oral rehydration solution (ORS). One third of the subjects (n = 100) were randomized to receive two liquid ounces of a taste and color-matched placebo diluted in eight ounces of ORS. The outcome variables measured included stool consistency, stomach discomfort, gas and bloating, and heartburn/indigestion. The study subjects ranked their stool consistency and the severity of their subjective symptoms at specified intervals from immediately prior to treatment, to five days post treatment. All subjects recorded their symptoms in a study diary. The study subjects also recorded the time and consistencies of all stools in their study diary. Stool consistency was compared to the picture and descriptions on the Bristol Stool Chart, and any stool rated greater than Type 4 was considered unformed. The clinical study team reviewed the study diaries with subjects during daily follow-up calls and close-out visits, and recorded the data in case report forms. RESULTS: After receiving a single dose, Aliva treated subjects reported shorter median time to their last unformed stool (1 h 50 min) than placebo treated subjects (67 h 50 min.), a statistically significant difference [95%CI: -3178-(-2018), P = 0.000]. Aliva treated subjects also reported shorter median their time to last unformed stool (TTLUS) (1 hrs 50 min) than placebo treated subjects (67 h 50 min), which was also a statistically significant difference (P = 0.000).The percentage of subjects recording TTLUS was greater for those who received Aliva vs placebo at 30 min (P = 0.027), 2 h (P = 0.000), 24 h (P = 0.000), 48 h (P = 0.000), 72 h (P = 0.000), and 5 d (P = 0.000) post dose. There were 146 study subjects 14 years old or older, which was the criteria set for reliable self-reporting of subjective symptoms. Of those 146 subjects, 142 reported stomach pain and discomfort during screening. From 90 minutes [95%CI: -1.8-(-0.01), P = 0.048] through 5 d [95%CI: -3.4-(-1.9), P = 0.000), the subjects treated with Aliva experienced significantly less stomach pain and discomfort than those who received placebo. Of those same 146 participants, 114 subjects reported gas and bloating during screening. Similarly, subjects who received Aliva experienced significantly less gas and bloating from 2 h [95%CI: -1.7-(-0.39), P = 0.030] through 5 d (95%CI: -2.0-0.42, P = 0.005) compared with the placebo arm. CONCLUSION: In this double-blind, randomized clinical study, subjects with acute gastroenteritis receiving Aliva prebiotic showed significant and sustained improvement of multiple symptoms vs those receiving placebo.

Capillary electrophoretic separation-based approach to determine the labeling kinetics of oligodeoxynucleotides.

With the recent advances in electron microscopy (EM), computation, and nanofabrication, the original idea of reading DNA sequence directly from an image can now be tested. One approach is to develop heavy atom labels that can provide the contrast required for EM imaging. While evaluating tentative labels for the respective nucleobases in synthetic oligodeoxynucleotides (oligos), we developed a streamlined CE protocol to assess the label stability, reactivity, and selectivity. We report our protocol using osmium tetroxide 2,2'-bipyridine (Osbipy) as a thymidine (T) specific label. The observed rates show that the labeling process is kinetically independent of both the oligo length, and the base composition. The conditions, i.e. temperature, optimal Osbipy concentration, and molar ratio of reagents, to promote 100% conversion of the starting oligo to labeled product were established. Hence, the optimized conditions developed with the oligos could be leveraged to allow osmylation of effectively all Ts in ssDNA, while achieving minimal mislabeling. In addition, the approach and methods employed here may be adapted to the evaluation of other prospective contrasting agents/labels to facilitate next-generation DNA sequencing by EM.

Novel hexahydropyrrolo[3,4-c]pyrrole CCR5 antagonists.

Starting with a high-throughput screening lead, a novel series of CCR5 antagonists was developed utilizing an information-based approach. Improvement of pharmacokinetic properties for the series was pursued by SAR exploration of the lead template. The synthesis, SAR and biological profiles of the series are described.

Kinamycin Biosynthesis. Synthesis, Isolation, and Incorporation of Stealthin C, an Aminobenzo[b]fluorene.

A new intermediate in the biosynthesis of the benzo[b]fluorene antibiotic, kinamycin D, has been identified. 11-Amino-4,5,9-trihydroxy-2-methyl-10H-benzo[b]fluoren-10-one was synthesized and shown to be present in extracts of Streptomyces murayamaensisfermentations. A deuterated sample was prepared and shown to be specifically incorporated into kinamycin D. This new intermediate, now named stealthin C, is also the probable hydroxylation substrate for the biosynthesis of stealthin A by S. viridochromogenes.