Design and in vitro antibiofilm activity of propolis diffusion-controlled biopolymers.

In this study, a novel pH-sensitive hydrogel beads that is based on gelatin/sodium alginate/chitosan (GEL/SA/CS) loaded with propolis ethanolic extracts (PE) were synthesized. The swelling behavior of GEL/SA/CS hydrogel beads was studied in different pH solutions and compared with unloaded CS (GEL/SA) hydrogel beads. The in vitro release studies have been revealed using four different pH (1.3, 5.0, 6.0, and 6.8), a saliva environment (pH 6.8), a simulated gastric fluid (SGF) (pH 1.3), and a simulated intestinal fluid (SIF) (pH 6.8) to simulate the physiological conditions in gastrointestinal (GI) tract. Propolis-loaded hydrogel beads were found to be stable at pH 1.3, 5.0, 6.0, simulated saliva, SGF, and SIF mediums, whereas the beads lose their stability at pH 6.8 buffer solution. Tested microorganisms displayed greater sensitivity to PE-loaded hydrogel beads compared with pure propolis. Contrary to antimicrobial activity results, antibiofilm activity results of PE-loaded GEL/SA and GEL/SA/CS hydrogel beads were found at low levels. According to the obtained results, the propolis-loaded GEL/SA/CS hydrogel beads synthesized within this study can be used in the treatment of GI tract diseases such as oral mucositis, gastric ulcer, ulcerative colitis, and GI cancer, as controlled releasing carriers of propolis.

Improved synthesis of the bifunctional chelator p-SCN-Bn-HOPO.

The bifunctional ligand p-SCN-Bn-HOPO, which has four 1,2-hydroxypyridinone groups on a spermine backbone with an isothiocyanate linker, has been shown to be an efficient and stable chelator for Zr(iv) and, more importantly, the radioisotope 89Zr for use in radiolabeling antibodies for positron emission tomography (PET) imaging. Previous studies of 89Zr-HOPO-trastuzumab in mice showed low background, good tumor to organ contrast, and very low bone uptake which show p-SCN-Bn-HOPO to be an important next-generation bifunctional chelator for radioimmunoPET imaging with 89Zr. However, the reported synthesis of p-SCN-Bn-HOPO involves nine steps and multiple HPLC purifications with an overall yield of about 1.4%. Herein we report an improved and efficient synthesis of p-SCN-Bn-HOPO in four steps with 14.3% overall yield which will improve its availability for further biological studies and wider application in PET imaging. The new synthetic route also allows variation in linker length and chemistries which may be helpful in modifying in vivo clearance behaviors of future agents.

Comparison of relationship between histopathological, serological and biochemical parameters in patients with chronic hepatitis B infection.

OBJECTIVE: To demonstrate the relationship between liver histology, alanine aminotransferase (ALT)/aspartate aminotransferase (AST) and hepatitis B virus (HBV) DNA levels based on hepatitis B e antigen (HBeAg) seropositivity status in naive patients with chronic hepatitis B (CHB). MATERIALS AND METHOD: Naive patients with CHB admitted to our hospital between January 2012 and April 2014 were evaluated retrospectively. The patients were allocated into one of two groups based on HBeAg-seropositivity status. RESULTS: Two hundred and fourteen patients were enrolled in the study. Of these 214 patients, 103 (48.1%) were HBeAg-positive and 111 (51.9%) were HBeAg-negative. In the HBeAg-positive group, positive correlations were found between histologic activity index (HAI) scores and ALT (t=3.3, r=0.31, p=0.001), AST (t=2.8, r=0.27, p=0.005) and HBV DNA load (t=2.5, r=0.24, p=0.014). Additionally, in this group, fibrosis scores had positive correlations with ALT (t=3.3, r=0.32, p=0.001) and AST (t=2.7, r=0.26, p=0.008). In the HBeAg-negative group, positive correlations were found between HAI scores and ALT (t=3, r=0. 28, p=0.003), AST (t=3, r=0. 28, p=0.003) and HBV DNA (t=5.3, r=0. 45, p=0). In this same group, fibrosis scores had a positive correlation with HBV DNA (t=2.2, r=0. 21, p=0.024). Multivariate logistic regression analysis showed a positive relationship between fibrosis and ALT in the HBeAg-positive group and a positive relationship between fibrosis and HBV DNA load in the HBeAg-negative group. CONCLUSIONS: This study showed that HBV DNA load is an independent predictive factor for evaluating HAI and fibrosis in the HBeAg-negative group. Also, ALT is an independent predictive factor for evaluating fibrosis in the HBeAg-positive group.

p-SCN-Bn-HOPO: A Superior Bifunctional Chelator for (89)Zr ImmunoPET.

Zirconium-89 has an ideal half-life for use in antibody-based PET imaging; however, when used with the chelator DFO, there is an accumulation of radioactivity in the bone, suggesting that the (89)Zr(4+) cation is being released in vivo. Therefore, a more robust chelator for (89)Zr could reduce the in vivo release and the dose to nontarget tissues. Evaluation of the ligand 3,4,3-(LI-1,2-HOPO) demonstrated efficient binding of (89)Zr(4+) and high stability; therefore, we developed a bifunctional derivative, p-SCN-Bn-HOPO, for conjugation to an antibody. A Zr-HOPO crystal structure was obtained showing that the Zr is fully coordinated by the octadentate HOPO ligand, as expected, forming a stable complex. p-SCN-Bn-HOPO was synthesized through a novel pathway. Both p-SCN-Bn-HOPO and p-SCN-Bn-DFO were conjugated to trastuzumab and radiolabeled with (89)Zr. Both complexes labeled efficiently and achieved specific activities of approximately 2 mCi/mg. PET imaging studies in nude mice with BT474 tumors (n = 4) showed good tumor uptake for both compounds, but with a marked decrease in bone uptake for the (89)Zr-HOPO-trastuzumab images. Biodistribution data confirmed the lower bone activity, measuring 17.0%ID/g in the bone at 336 h for (89)Zr-DFO-trastuzumab while (89)Zr-HOPO-trastuzumab only had 2.4%ID/g. We successfully synthesized p-SCN-Bn-HOPO, a bifunctional derivative of 3,4,3-(LI-1,2-HOPO) as a potential chelator for (89)Zr. In vivo studies demonstrate the successful use of (89)Zr-HOPO-trastuzumab to image BT474 breast cancer with low background, good tumor to organ contrast, and, importantly, very low bone uptake. The reduced bone uptake seen with (89)Zr-HOPO-trastuzumab suggests superior stability of the (89)Zr-HOPO complex.

Synthese and characterization of boronic acid functionalized macroporous uniform poly(4-chloromethylstyrene-co-divinylbenzene) particles and its use in the isolation of antioxidant compounds from plant extracts.

Aminophenyl boronic acid (APBA) carrying uniform-macroporous poly(chloromethylstyrene-co-divinylbenzene), poly(CMS-co-DVB) particles were synthesized for selective separation of cis-diol-containing flavonoids from plant extracts. For this purpose, 2.5 µm polystyrene seed particles were first swelled by a mixture of dibutyl phthalate (DBP), toluene and dodecanol, then by a monomer mixture including CMS and DVB. The repolymerization of the monomer phase in the swollen seed particles provided macroporous and uniform particles, approximately 7 µm in size. Chlorine atoms on the surface of these particles were derivatized with APBA to gain affinity properties for flavonoids containing vicinal hydroxyl groups. Model adsorption studies showed that these particles selectively adsorbed quercetin and rutin containing cis-diol groups, but did not adsorb apigenin similar to quercetin and not carrying cis-diol groups. These particles were also tested in adsorption/desorption studies for ethanol and ethyl acetate extracts of the Hypericum perforatum (HP) stems to obtain high antioxidant mixtures. With ethanol extract, the antioxidant activity of the desorption solution was a bit higher than that of the post-adsorption solutions. However, the DPPH radical scavenging activity of the desorption solution decreased with respect to the original extract and post-adsorption solutions. A similar result was obtained for the antioxidant activity of the desorption solution using ethyl acetate extract. An interesting result was obtained that DPPH radical scavenging activity of the post-adsorption solution was higher than that of the original ethyl acetate extract and desorption solutions. These results were attributed to selective adsorption of antioxidant characterized cis-diol-containing apolar molecules much more rather than that radical scavenger characterized polar molecules.