A proprietary alpha-amylase inhibitor from white bean (Phaseolus vulgaris): A review of clinical studies on weight loss and glycemic control

Obesity, and resultant health hazards which include diabetes, cardiovascular disease and metabolic syndrome, are worldwide medical problems. Control of diet and exercise are cornerstones of the management of excess weight. Foods with a low glycemic index may reduce the risk of diabetes and heart disease as well as their complications. As an alternative to a low glycemic index diet, there is a growing body of research into products that slow the absorption of carbohydrates through the inhibition of enzymes responsible for their digestion. These products include alpha-amylase and glucosidase inhibitors. The common white bean (Phaseolus vulgaris) produces an alpha-amylase inhibitor, which has been characterized and tested in numerous clinical studies. A specific and proprietary product named Phase 2^® Carb Controller (Pharmachem Laboratories, Kearny, NJ) has demonstrated the ability to cause weight loss with doses of 500 to 3000 mg per day, in either a single dose or in divided doses. Clinical studies also show that Phase 2 has the ability to reduce the post-prandial spike in blood glucose levels. Experiments conducted incorporating Phase 2 into food and beverage products have found that it can be integrated into various products without losing activity or altering the appearance, texture or taste of the food. There have been no serious side effects reported following consumption of Phase 2. Gastro-intestinal side effects are rare and diminish upon extended use of the product. In summary, Phase 2 has the potential to induce weight loss and reduce spikes in blood sugar caused by carbohydrates through its alpha-amylase inhibiting activity.     

Stable dye-labelled oligonucleotide-nanoparticle conjugates for nucleic acid detection

Metallic nanoparticles functionalized with oligonucleotides are used for a number of nucleic acid detection strategies. However, oligonucleotide-nanoparticle conjugates suffer from a lack of stability when exposed to certain conditions associated with DNA detection assays. In this study, we report the synthesis of thiol and thioctic acid-modified oligonucleotide gold nanoparticle (OGNs) conjugates functionalized with a dye label and varying spacer groups. The thioctic acid-modified conjugates exhibit increased stability when treated with dithiothreitol (DTT) compared to the more commonly used thiol modification. When the dye labelled oligonucleotide nanoparticle conjugates are exposed to the same conditions there is a pronounced increase in the stability for both thioctic acid and thiol modified sequences. These results open up the possibility of simply using a dye label to enhance the stability of oligonucleotide-nanoparticle conjugates in DNA detection assays where the enhanced stability of the conjugate system can be advantageous in more complex biological environments.     

A facile spin-cast route for cation exchange of multilayer perpendicularly-aligned nanorod assemblies

A facile spin cast route was developed to convert perpendicularly aligned nanorod assemblies of cadmium chalcogenides into their silver and copper analogues. The assemblies are rapidly cation exchanged without affecting either the individual rod dimensions or collective superlattice order extending over several multilayers.     

Implementation of the waste reduction (WAR) algorithm utilizing flowsheet monitoring

Environmental metric software can be used to evaluate the sustainability of a chemical based upon data from the chemical process used to manufacture it. An obstacle to the development of environmental metric software for use in chemical process modeling software has been the inability to obtain information about the process directly from the model. There have been past attempts to develop environmental metrics that make use of the process models, but there has not been an integrated, standardized approach to obtaining the process information required for calculating metrics. As a result, environmental evaluation packages are largely limited to use in a single simulation package, further limiting the development and adoption of these tools.This paper proposes a standardized mechanism for obtaining process information directly from a process model using a strongly integrated interface set, called flowsheet monitoring. The flowsheet monitoring interface provides read-only access to the unit operation and streams within the process model, and can be used to obtain the material flow data from the process streams. This material flow data can then be used to calculate process-based environmental metrics. The flowsheet monitoring interface has been proposed as an extension of the CAPE-OPEN chemical process simulation interface set.To demonstrate the capability of the flowsheet monitoring interfaces, the US Environmental Protection Agency (USEPA) WAste Reduction (WAR) algorithm is demonstrated in AmsterCHEM's COFE (CAPE-OPEN Flowsheeting Environment). The WAR add-in accesses the material flows and unit operations directly from the process simulator and uses flow data to calculate the potential environmental impact (PEI) score for the process. The WAR algorithm add-in is included in the latest release of COCO Simulation Environment, available from http://www.cocosimulator.org/.     

DNA Break Mapping Reveals Topoisomerase II Activity Genome-Wide

Genomic DNA is under constant assault by endogenous and exogenous DNA damaging agents. DNA breakage can represent a major threat to genome integrity but can also be necessary for genome function. Here we present approaches to map DNA double-strand breaks (DSBs) and single-strand breaks (SSBs) at the genome-wide scale by two methods called DSB- and SSB-Seq, respectively. We tested these methods in human colon cancer cells and validated the results using the Topoisomerase II (Top2)-poisoning agent etoposide (ETO). Our results show that the combination of ETO treatment with break-mapping techniques is a powerful method to elaborate the pattern of Top2 enzymatic activity across the genome.     

Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner

Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics.     

Synthesis and Biological Evaluation of CTP Synthetase Inhibitors as Potential Agents for the Treatment of African Trypanosomiasis

Acivicin analogues with an increased affinity for CTP synthetase (CTPS) were designed as potential new trypanocidal agents. The inhibitory activity against CTPS can be improved by increasing molecular complexity, by inserting groups able to establish additional interactions with the binding pocket of the enzyme. This strategy has been pursued with the synthesis of α‐amino‐substituted analogues of Acivicin and N1‐substituted pyrazoline derivatives. In general, there is direct correlation between the enzymatic activity and the in vitro anti‐trypanosomal efficacy of the derivatives studied here. However, this cannot be taken as a general rule, as other important factors may play a role, notably the ability of uptake/diffusion of the molecules into the trypanosomes.     

Novel Positive Allosteric Modulators of µ Opioid Receptor—Insight from In Silico and In Vivo Studies

Opioids are the drugs of choice in severe pain management. Unfortunately, their use involves serious, potentially lethal side effects. Therefore, efforts in opioid drug design turn toward safer and more effective mechanisms, including allosteric modulation. In this study, molecular dynamics simulations in silico and ‘writhing’ tests in vivo were used to characterize potential allosteric mechanism of two previously reported compounds. The results suggest that investigated compounds bind to μ opioid receptor in an allosteric site, augmenting action of morphine at subeffective doses, and exerting antinociceptive effect alone at higher doses. Detailed analysis of in silico calculations suggests that first of the compounds behaves more like allosteric agonist, while the second compound acts mainly as a positive allosteric modulator.     

Yttrium incorporation in Cr2AlC: On the metastable phase formation and decomposition of (Cr,Y)2AlC MAX phase thin films

Herein we report on the synthesis of a metastable (Cr,Y)₂AlC MAX phase solid solution by co-sputtering from a composite Cr–Al–C and elemental Y target, at room temperature, followed by annealing. However, direct high-temperature synthesis resulted in multiphase films, as evidenced by X-ray diffraction analyses, room-temperature depositions, followed by annealing to 760°C led to the formation of phase pure (Cr,Y)₂AlC by diffusion. Higher annealing temperatures caused a decomposition of the metastable phase into Cr₂AlC, Y₅Al₃, and Cr-carbides. In contrast to pure Cr₂AlC, the Y-containing phase crystallizes directly in the MAX phase structure instead of first forming a disordered solid solution. Furthermore, the crystallization temperature was shown to be Y-content dependent and was increased by ∼200°C for 5 at.% Y compared to Cr₂AlC. Calculations predicting the metastable phase formation of (Cr,Y)₂AlC and its decomposition are in excellent agreement with the experimental findings.