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Clinical and Parasitological Effects of Aspilia africana (Pers.) C.D. Adams in Fifteen Patients with Uncomplicated Malaria

This paper reports the findings of a clinical study of a herbal preparation of Aspilia africana (Pers.) C.D. Adams against malaria, corroborated by in vitro antiplasmodial and cytotoxicity tests. In a non-controlled prospective design, 15 patients with uncomplicated malaria were administered with the herbal preparation and assessed for clinical manifestations of malaria, parasitaemia and global quality of life using the Kanorfsky Performance Scale. Antiplasmodial activity of extracts against the chloroquine-resistant strain of Plasmodium falciparum Dd2 was determined using the [3H]-hypoxanthine radioactive method while cytotoxicity against human urinary bladder carcinoma (ECV-304) and human hepatocellular carcinoma (HepG2) cell lines was determined using the MTT assay. Remarkable clinical improvements occurred 3 to 21 days after initiation of treatment. Forty nine days after starting treatment, all 15 patients had complete resolution of malaria symptoms and were cleared of parasitaemia and attained a Karnofsky Performance score of 100. The petroleum ether/ethyl acetate extract possessed in vitro antiplasmodial activity (IC50 30μg/ml) but no remarkable cytotoxicity. The A. africana preparation shows potential as an alternative for the management of uncomplicated malaria.East and Central African Journal of Pharmaceutical Sciences Vol. 12 (2009) 37-4

In Vitro Aging of Human Skin Fibroblasts: Age-Dependent Changes in 4-Hydroxynonenal Metabolism

Evidence suggests that the increased production of free radicals and reactive oxygen species lead to cellular aging. One of the consequences is lipid peroxidation generating reactive aldehydic products, such as 4-hydroxynonenal (HNE) that modify proteins and form adducts with DNA bases. To prevent damage by HNE, it is metabolized. The primary metabolic products are the glutathione conjugate (GSH-HNE), the corresponding 4-hydroxynonenoic acid (HNA), and the alcohol 1,4-dihydroxynonene (DHN). Since HNE metabolism can potentially change during in vitro aging, cell cultures of primary human dermal fibroblasts from several donors were cultured until senescence. After different time points up to 30 min of incubation with 5 \ub5M HNE, the extracellular medium was analyzed for metabolites via liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS). The metabolites appeared in the extracellular medium 5 min after incubation followed by a time-dependent increase. But, the formation of GSH-HNL and GSH-DHN decreased with increasing in vitro age. As a consequence, the HNE levels in the cells increase and there is more protein modification observed. Furthermore, after 3 h of incubation with 5 \ub5M HNE, younger cells showed less proliferative capacity, while in older cells slight increase in the mitotic index was noticed

Amorfrutin B is an efficient natural peroxisome proliferator-activated receptor gamma (PPARgamma) agonist with potent glucose-lowering properties

AIMS/HYPOTHESIS: The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is an important gene regulator in glucose and lipid metabolism. Unfortunately, PPARgamma-activating drugs of the thiazolidinedione class provoke adverse side effects. As recently shown, amorfrutin A1 is a natural glucose-lowering compound that selectively modulates PPARgamma. In this study we aimed to characterise, in vitro, a large spectrum of the amorfrutins and similar molecules, which we isolated from various plants. We further studied in vivo the glucose-lowering effects of the so far undescribed amorfrutin B, which featured the most striking PPARgamma-binding and pharmacological properties of this family of plant metabolites. METHODS: Amorfrutins were investigated in vitro by binding and cofactor recruitment assays and by transcriptional activation assays in primary human adipocytes and murine preosteoblasts, as well as in vivo using insulin-resistant high-fat-diet-fed C57BL/6 mice treated for 27 days with 100 mg kg(-1) day(-1) amorfrutin B. RESULTS: Amorfrutin B showed low nanomolar binding affinity to PPARgamma, and micromolar binding to the isotypes PPARalpha and PPARbeta/delta. Amorfrutin B selectively modulated PPARgamma activity at low nanomolar concentrations. In insulin-resistant mice, amorfrutin B considerably improved insulin sensitivity, glucose tolerance and blood lipid variables after several days of treatment. Amorfrutin B treatment did not induce weight gain and furthermore showed liver-protecting properties. Additionally, amorfrutins had no adverse effects on osteoblastogenesis and fluid retention. CONCLUSIONS/INTERPRETATION: The application of plant-derived amorfrutins or synthetic analogues thereof constitutes a promising approach to prevent or treat complex metabolic diseases such as insulin resistance or type 2 diabetes

Ion-pairing chromatography and amine derivatization provide complementary approaches for the targeted LC-MS analysis of the polar metabolome.

Liquid chromatography coupled to mass spectrometry is a key metabolomics/metabonomics technology. Reversed-phase liquid chromatography (RPLC) is very widely used as a separation step, but typically has poor retention of highly polar metabolites. Here, we evaluated the combination of two alternative methods for improving retention of polar metabolites based on 6-aminoquinoloyl-N-hydroxysuccinidimyl carbamate derivatization for amine groups, and ion-pairing chromatography (IPC) using tributylamine as an ion-pairing agent to retain acids. We compared both of these methods to RPLC and also to each other, for targeted analysis using a triple-quadrupole mass spectrometer, applied to a library of ca. 500 polar metabolites. IPC and derivatization were complementary in terms of their coverage: combined, they improved the proportion of metabolites with good retention to 91%, compared to just 39% for RPLC alone. The combined method was assessed by analyzing a set of liver extracts from aged male and female mice that had been treated with the polyphenol compound ampelopsin. Not only were a number of significantly changed metabolites detected, but also it could be shown that there was a clear interaction between ampelopsin treatment and sex, in that the direction of metabolite change was opposite for males and females

Conservation and divergence of myelin proteome and oligodendrocyte transcriptome profiles between humans and mice

Human myelin disorders are commonly studied in mouse models. Since both clades evolutionarily diverged approximately 85 million years ago, it is critical to know to what extent the myelin protein composition has remained similar. Here, we use quantitative proteomics to analyze myelin purified from human white matter and find that the relative abundance of the structural myelin proteins PLP, MBP, CNP, and SEPTIN8 correlates well with that in C57Bl/6N mice. Conversely, multiple other proteins were identified exclusively or predominantly in human or mouse myelin. This is exemplified by peripheral myelin protein 2 (PMP2), which was specific to human central nervous system myelin, while tetraspanin-2 (TSPAN2) and connexin-29 (CX29/GJC3) were confined to mouse myelin. Assessing published scRNA-seq-datasets, human and mouse oligodendrocytes display well-correlating transcriptome profiles but divergent expression of distinct genes, including Pmp2, Tspan2, and Gjc3. A searchable web interface is accessible via www.mpinat.mpg.de/myelin. Species-dependent diversity of oligodendroglial mRNA expression and myelin protein composition can be informative when translating from mouse models to humans

Tourist Shoppers’ Evaluation of Retail Service: A Study of Cross-Border versus International Outshoppers

This article extends the concept of customer perceived value (CPV) to the tourist outshopping context and explores the differences in antecedents and outcomes of CPV between cross-border and international outshoppers. A large-scale field survey in Hong Kong with cross-border outshoppers from mainland China and international shoppers from four Western countries (Australia, Canada, the United Kingdom, and the United States) shows that perceived product quality, risk, and value for money have a stronger effect on CPV for cross-border outshoppers, and employee service quality and lifestyle congruence for international outshoppers. CPV also has a stronger positive effect on satisfaction, word of mouth, and repeat purchase intentions for cross-border outshoppers, whereas satisfaction has a stronger positive impact on word of mouth and repeat purchase intentions for international outshoppers. We discuss the conceptual contribution and managerial implications of our findings for international retailers, researchers, and tourism organizations

Compact Chirped Fiber Bragg Gratings for Single-Photon Generation from Quantum Dots

A scalable source of single photons is a key constituent of an efficient quantum photonic architecture. To realize this, it is beneficial to have an ensemble of quantum emitters that can be collectively excited with high efficiency. Semiconductor quantum dots hold great potential in this context, due to their excellent photophysical properties. Spectral variability of quantum dots is commonly regarded as a drawback introduced by the fabrication method. However, this is beneficial to realize a frequency-multiplexed single-photon platform. Chirped pulse excitation, relying on the so-called adiabatic rapid passage, is the most efficient scheme to excite a quantum dot ensemble due to its immunity to individual quantum dot parameters. Yet, the existing methods of generating chirped laser pulses to excite a quantum emitter are bulky, lossy, and mechanically unstable, which severely hampers the prospects of a quantum dot photon source. Here, we present a compact, robust, and high-efficiency alternative for chirped pulse excitation of solid-state quantum emitters. Our simple plug-and-play module consists of chirped fiber Bragg gratings (CFBGs), fabricated via femtosecond inscription, to provide high values of dispersion in the near-infrared spectral range, where the quantum dots emit. We characterize and benchmark the performance of our method via chirped excitation of a GaAs quantum dot, establishing high-fidelity single-photon generation. Our highly versatile chirping module coupled to a photon source is a significant milestone toward realizing practical quantum photonic devices