Concerted suppressive effects of carisbamate, an anti-epileptic alkyl-carbamate drug, on voltage-gated Na+ and hyperpolarization-activated cation currents

Carisbamate (CRS, RWJ-333369) is a new anti-seizure medication. It remains unclear whether and how CRS can perturb the magnitude and/or gating kinetics of membrane ionic currents, despite a few reports demonstrating its ability to suppress voltage-gated Na+ currents. In this study, we observed a set of whole-cell current recordings and found that CRS effectively suppressed the voltage-gated Na+ (INa) and hyperpolarization-activated cation currents (Ih) intrinsically in electrically excitable cells (GH3 cells). The effective IC50 values of CRS for the differential suppression of transient (INa(T)) and late INa (INa(L)) were 56.4 and 11.4 μM, respectively. However, CRS strongly decreased the strength (i.e., Δarea) of the nonlinear window component of INa (INa(W)), which was activated by a short ascending ramp voltage (Vramp); the subsequent addition of deltamethrin (DLT, 10 μM) counteracted the ability of CRS (100 μM, continuous exposure) to suppress INa(W). CRS strikingly decreased the decay time constant of INa(T) evoked during pulse train stimulation; however, the addition of telmisartan (10 μM) effectively attenuated the CRS (30 μM, continuous exposure)-mediated decrease in the decay time constant of the current. During continued exposure to deltamethrin (10 μM), known to be a pyrethroid insecticide, the addition of CRS resulted in differential suppression of the amplitudes of INa(T) and INa(L). The amplitude of Ih activated by a 2-s membrane hyperpolarization was diminished by CRS in a concentration-dependent manner, with an IC50 value of 38 μM. For Ih, CRS altered the steady-state I–V relationship and attenuated the strength of voltage-dependent hysteresis (Hys(V)) activated by an inverted isosceles-triangular Vramp. Moreover, the addition of oxaliplatin effectively reversed the CRS-mediated suppression of Hys(V). The predicted docking interaction between CRS and with a model of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel or between CRS and the hNaV1.7 channel reflects the ability of CRS to bind to amino acid residues in HCN or hNaV1.7 channel via hydrogen bonds and hydrophobic interactions. These findings reveal the propensity of CRS to modify INa(T) and INa(L) differentially and to effectively suppress the magnitude of Ih. INa and Ih are thus potential targets of the actions of CRS in terms of modulating cellular excitability

Enhancing the efficiency of a PCR using gold nanoparticles

We found that the PCR could be dramatically enhanced by Au nanoparticles. With the addition of 0.7 nM of 13 nm Au nanoparticles into the PCR reagent, the PCR efficiency was increased. Especially when maintaining the same or higher amplification yields, the reaction time could be shortened, and the heating/cooling rates could be increased. The excellent heat transfer property of the nanoparticles should be the major factor in improving the PCR efficiency. Different PCR systems, DNA polymerases, DNA sizes and complex samples were compared in this study. Our results demonstrated that Au nanoparticles increase the sensitivity of PCR detection 5- to 10-fold in a slower PCR system (i.e. conventional PCR) and at least 10(4)-fold in a quicker PCR system (i.e. real-time PCR). After the PCR time was shortened by half, the 100 copies/µl DNA were detectable in real-time PCR with gold colloid added, however, at least 10(6) copies/µl of DNA were needed to reach a detectable signal level using the PCR reagent without gold colloid. This innovation could improve the PCR efficiency using non-expensive polymerases, and general PCR reagent. It is a new viewpoint in PCR, that nanoparticles can be used to enhance PCR efficiency and shorten reaction times

Signs of outflow feedback from a nearby young stellar object on the protostellar envelope around HL Tau

HL Tau is a Class I-II protostar embedded in an infalling and rotating envelope and possibly associated with a planet forming disk, and it is co-located in a 0.1 pc molecular cloud with two nearby young stellar objects. Our ALMA observations revealed two arc-like structures on a 1000 au scale connected to the disk, and their kinematics could not be explained with any conventional model of infalling and rotational motions. In this work, we investigate the nature of these arc-like structures connected to the HL Tau disk. We conducted new observations in the 13CO and C18O (3-2; 2-1) lines with JCMT and IRAM 30m, and obtained the ACA data with the 7-m array. With the single-dish, ACA, and ALMA data, we analyzed the gas motions on both 0.1 pc and 1000 au scales in the HL Tau region. We constructed new kinematical models of an infalling and rotating envelope with the consideration of relative motion between HL Tau and the envelope. By including the relative motion between HL Tau and its protostellar envelope, our kinematical model can explain the observed velocity features in the arc-like structures. The morphologies of the arc-like structures can also be explained with an asymmetric initial density distribution in our model envelope. In addition, our single-dish results support that HL Tau is located at the edge of a large-scale (0.1 pc) expanding shell driven by the wind or outflow from XZ Tau, as suggested in the literature. The estimated expanding velocity of the shell is comparable to the relative velocity between HL Tau and its envelope in our kinematical model. These results hints that the large-scale expanding motion likely impacts the protostellar envelope around HL Tau and affects its gas kinematics. We found that the mass infalling rate from the envelope onto the HL Tau disk can be decreased by a factor of two due to this impact by the large-scale expanding shell.Comment: Accepted by A&

Effects of manual lymphatic drainage on breast cancer-related lymphedema: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Lymphedema is a common complication of axillary dissection for breast cancer. We investigated whether manual lymphatic drainage (MLD) could prevent or manage limb edema in women after breast-cancer surgery. METHODS: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the effectiveness of MLD in the prevention and treatment of breast-cancer-related lymphedema. The PubMed, EMBASE, CINAHL, Physiotherapy Evidence Database (PEDro), SCOPUS, and Cochrane Central Register of Controlled Trials electronic databases were searched for articles on MLD published before December 2012, with no language restrictions. The primary outcome for prevention was the incidence of postoperative lymphedema. The outcome for management of lymphedema was a reduction in edema volume. RESULTS: In total, 10 RCTs with 566 patients were identified. Two studies evaluating the preventive outcome of MLD found no significant difference in the incidence of lymphedema between the MLD and standard treatment groups, with a risk ratio of 0.63 and a 95% confidence interval (CI) of 0.14 to 2.82. Seven studies assessed the reduction in arm volume, and found no significant difference between the MLD and standard treatment groups, with a weighted mean difference of 75.12 (95% CI, −9.34 to 159.58). CONCLUSIONS: The current evidence from RCTs does not support the use of MLD in preventing or treating lymphedema. However, clinical and statistical inconsistencies between the various studies confounded our evaluation of the effect of MLD on breast-cancer-related lymphedema