Safety of herbal medicinal products: Echinacea and selected alkylamides do not induce CYP3A4 mRNA expression

Copyright © 2011 Maryam Modarai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.A major safety concern with the use of herbal medicinal products (HMP) is their interactions with conventional medicines, which are often mediated via the cytochrome P450 (CYP) system. Echinacea is a widely used over-the-counter HMP, with proven immunomodulatory properties. Its increasing use makes research into its safety an urgent concern. Previously, we showed that Echinacea extracts and its alkylamides (thought to be important for Echinacea's immunomodulatory activity) mildly inhibit the enzymatic activity of the main drug metabolising CYP isoforms, but to this date, there is insufficient work on its ability to alter CYP expression levels. We now report for the first time the effect of a commercial Echinacea extract (Echinaforce) and four Echinacea alkylamides on the transcription of the major drug metabolizing enzyme CYP3A4. HepG2 cells were exposed for 96 h to clinically relevant concentrations of Echinaforce (22, 11.6 and 1.16g mL-1) or the alkylamides (1.62 and 44 nM). CYP3A4 mRNA levels were quantified using real-time reverse transcription polymerase chain reaction (RT-PCR). Neither Echinaforce nor the alkylamides produced any significant changes in the steady-state CYP3A4 mRNA levels, under these conditions. In contrast, treatment with 50M rifampicin resulted in a 3.8-fold up-regulation over the vehicle control. We conclude that Echinaforce is unlikely to affect CYP3A4 transcriptional levels, even at concentrations which can inhibit the enzymatic activity of CYP3A4. Overall, our data provides further evidence for the lack of interactions between Echinacea and conventional drugs.Bioforce, Switzerland and the Maplethorpe Trust (University of London)

Concatenated dynamical decoupling with virtual pulses

The loss of quantum information due to interaction with external degrees of freedom, which is known as decoherence, remains one of the main obstacles for large-scale implementations of quantum computing. Accordingly, different measures are being explored for reducing its effect. One of them is dynamical decoupling (DD) which offers a practical solution because it only requires the application of control pulses to the system qubits. Starting from basic DD sequences, more sophisticated schemes were developed that eliminate higher-order terms of the system-environment interaction and are also more robust against experimental imperfections. A particularly successful scheme, called concatenated DD (CDD), gives a recipe for generating higher order sequences by inserting lower order sequences into the delays of a generating sequence. Here, we show how this scheme can be improved further by converting some of the pulses to virtual (and thus ideal) pulses. The resulting scheme, called vCDD, has lower power deposition and is more robust against pulse imperfections than the original CDD scheme.Comment: 9 pages, 9 figure

Almost Routine Prophylactic Cholecystectomy During Laparoscopic Gastric Bypass is Safe

Background: Morbidly obese patients are at high risk to develop gallstones, and rapid weight loss after bariatric surgery further enhances this risk. The concept of prophylactic cholecystectomy during gastric bypass has been challenged recently because the risk may be lower than reported earlier and because cholecystectomy during laparoscopic gastric bypass may be more difficult and risky. Methods: A review of prospectively collected data on 772 patients who underwent laparoscopic primary gastric bypass between January 2000 and August 2007 was performed. The charts of patients operated before 2004 were retrospectively reviewed regarding preoperative echography and histopathological findings. Results: Fifty-eight (7.5%) patients had had previous cholecystectomy. In the remaining patients, echography showed gallstones or sludge in 81 (11.3%). Cholecystectomy was performed at the time of gastric bypass in 665 patients (91.7%). Gallstones were found intraoperatively in 25 patients (3.9%), for a total prevalence of gallstones of 21.2%. The age of patients with gallstones was higher than that of gallstone-free patients (43.5 vs 38.7years, p < 0.0001). Of the removed specimens, 81.8% showed abnormal histologic findings, mainly chronic cholecystitis and cholesterolosis. Cholecystectomy was associated with no procedure-related complication, prolonged duration of surgery by a mean of 19min (4-45), and had no effect on the duration of hospital stay. Cholecystectomy was deemed too risky in 59 patients (8.3%) who were prescribed a 6-month course of ursodeoxycolic acid. Conclusion: Concomitant cholecystectomy can be performed safely in most patients during laparoscopic gastric bypass and does not prolong hospital stay. As such, it is an acceptable form of prophylaxis against stones forming during rapid weight loss. Whether it is superior to chemical prophylaxis remains to be demonstrated in a large prospective randomized stud

Separation of quadrupolar and magnetic contributions to spin-lattice relaxation in the case of a single isotope

We present a NMR pulse double-irradiation method which allows one to separate magnetic from quadrupolar contributions in the spin-lattice relaxation. The pulse sequence fully saturates one transition while another is observed. In the presence of a Delta m = 2 quadrupolar contribution, the intensity of the observed line is altered compared to a standard spin-echo experiment. We calculated analytically this intensity change for spins I=1, 3/2, 5/2, thus providing a quantitative analysis of the experimental results. Since the pulse sequence we used takes care of the absorbed radio-frequency power, no problems due to heating arise. The method is especially suited when only one NMR sensitive isotope is available. Different cross-checks were performed to prove the reliability of the obtained results. The applicability of this method is demonstrated by a study of the plane oxygen 17O (I = 5/2) in the high-temperature superconductor YBa_2Cu_4O_8: the 17O spin-lattice relaxation rate consists of magnetic as well as quadrupolar contributions.Comment: 7 pages, 6 figure

Nuclear spin qubits in a trapped-ion quantum computer

Physical systems must fulfill a number of conditions to qualify as useful quantum bits (qubits) for quantum information processing, including ease of manipulation, long decoherence times, and high fidelity readout operations. Since these conditions are hard to satisfy with a single system, it may be necessary to combine different degrees of freedom. Here we discuss a possible system, based on electronic and nuclear spin degrees of freedom in trapped ions. The nuclear spin yields long decoherence times, while the electronic spin, in a magnetic field gradient, provides efficient manipulation, and the optical transitions of the ions assure a selective and efficient initialization and readout.Comment: 7 page

NMR quantum simulation of localization effects induced by decoherence

The loss of coherence in quantum mechanical superposition states limits the time for which quantum information remains useful. Similarly, it limits the distance over which quantum information can be transmitted, resembling Anderson localization, where disorder causes quantum mechanical states to become localized. Here, we investigate in a nuclear spin-based quantum simulator, the localization of the size of spin clusters that are generated by a Hamiltonian driving the transmission of information, while a variable-strength perturbation counteracts the spreading. We find that the system reaches a dynamic equilibrium size, which decreases with the square of the perturbation strength.Comment: 5 pages, 5 figure