Influence of anti-epileptic drugs on hematological and biochemical parameters in patients with epilepsy

Background: Epilepsy is a chronic neurological condition which may require long-term treatment with antiepileptic drugs (AEDs). The challenge in AED management is to attain freedom from seizures, without side-effects and with good quality-of-life. However, AEDs are reported to induce potential adverse effects, which can remain unnoticed over long time. In this regard, earlier studies report inconsistent results in hematological and biochemical toxicity of AEDs. The objective of the present study was to evaluate the effects of AED monotherapy and polytherapy on hematological and biochemical parameters.Methods: This was a cross-sectional, observational study carried out among patients with epilepsy (PWE) receiving AEDs. The data on baseline demographic characteristics, treatment, adverse drug reactions, hematological, and biochemical investigations were collected. Statistical analysis was performed using the SPSS version 18 and descriptive statistics such as mean and median were used to summarize the data and inferential tests like Chi-square was used to compare categorical variables between groups.Results: There were 255 PWE in mean age range of 28.68±9.29 years, with 56.54% males. A total of 78.04% had focal, 18.04% had generalized seizures and remaining 3.92% were unclassified. Majority of (55.69%) PWE received polytherapy with AEDs. Females had significantly lower levels of hemoglobin (Hb) when compared with males (p=0.000), and patients on AED polytherapy showed significant difference in low Hb (p=0.006) and high alkaline phosphatase (ALP) levels (p=0.001).Conclusions: The results of this study showed significant alterations in the levels of Hb and ALP with the use of AED polytherapy in PWE. Routine hematological and biochemical investigations may be considered during AED treatment in those patients receiving AED polytherapy

Life support systems analysis and technical trades for a lunar outpost

The NASA/JPL life support systems analysis (LISSA) software tool was used to perform life support system analysis and technology trades for a Lunar Outpost. The life support system was modeled using a chemical process simulation program on a steady-state, one-person, daily basis. Inputs to the LiSSA model include metabolic balance load data, hygiene load data, technology selection, process operational assumptions and mission parameter assumptions. A baseline set of technologies has been used against which comparisons have been made by running twenty-two cases with technology substitutions. System, subsystem, and technology weights and powers are compared for a crew of 4 and missions of 90 and 600 days. By assigning a weight value to power, equivalent system weights are compared. Several less-developed technologies show potential advantages over the baseline. Solid waste treatment technologies show weight and power disadvantages but one could have benefits associated with the reduction of hazardous wastes and very long missions. Technology development towards reducing the weight of resupplies and lighter materials of construction was recommended. It was also recommended that as technologies are funded for development, contractors should be required to generate and report data useful for quantitative technology comparisons

Natural history and clinical effect of aortic valve regurgitation after left ventricular assist device implantation

ObjectivesAortic valve regurgitation reduces left ventricular assist device mechanical efficiency. Evidence has also suggested that left ventricular assist device implantation can induce or exacerbate aortic valve regurgitation. However, this has not been compared with aortic valve regurgitation progression in a nonsurgical end-stage heart failure population. Furthermore, its clinical effect is unclear. We sought to characterize the development and progression of aortic valve regurgitation in left ventricular assist device recipients and to identify its clinical effect.MethodsA review of all consecutive patients who received an intracorporeal left ventricular assist device at Duke University Medical Center from January 2004 to January 2011 was conducted. Cases of previous or concomitant aortic valve surgery were excluded. Data from the remaining implants (n = 184) and a control group of contemporaneous nonsurgical patients with end-stage heart failure (n = 132) were analyzed. Serial transthoracic echocardiography was used to characterize aortic valve regurgitation as a function of time.ResultsLeft ventricular assist device implantation was associated with worsening aortic valve regurgitation, defined as an increase in aortic valve regurgitation grade, relative to the nonsurgical patients with end-stage heart failure (P < .0001). The recipients of continuous flow left ventricular assist devices were more likely than recipients of pulsatile left ventricular assist devices to develop worsening aortic valve regurgitation (P = .0348). Moderate or severe aortic valve regurgitation developed in 21 left ventricular assist device recipients; this was unrelated to the type of device implanted (continuous vs pulsatile; P = .754) or aortic valve regurgitation grade before left ventricular assist device implantation (P = .42). Five patients developed severe aortic valve regurgitation; all of whom underwent aortic valve procedures.ConclusionsNative aortic valve regurgitation developed and/or progressed after left ventricular assist device implantation, with this effect being more pronounced in continuous flow left ventricular assist device recipients. However, the preoperative aortic valve regurgitation grade failed to correlate with the development of substantial aortic valve regurgitation after left ventricular assist device implantation. After left ventricular assist device implantation, aortic valve regurgitation had a small, but discernible, clinical effect, with some patients developing severe aortic valve regurgitation and requiring aortic valve procedures. These data have implications for the long-term management of left ventricular assist device recipients, in particular as the durability of implantable continuous flow left ventricular assist device therapy improves

Casein kinase I δ/ɛ phosphorylates topoisomerase IIα at serine-1106 and modulates DNA cleavage activity

We previously reported that phosphorylation of topoisomerase (topo) IIα at serine-1106 (Ser-1106) regulates enzyme activity and sensitivity to topo II-targeted drugs. In this study we demonstrate that phosphorylation of Ser-1106, which is flanked by acidic amino acids, is regulated in vivo by casein kinase (CK) Iδ and/or CKIɛ, but not by CKII. The CKI inhibitors, CKI-7 and IC261, reduced Ser-1106 phosphorylation and decreased formation of etoposide-stabilized topo II–DNA cleavable complex. In contrast, the CKII inhibitor, 5,6-dichlorobenzimidazole riboside, did not affect etoposide-stabilized topo II–DNA cleavable complex formation. Since, IC261 specifically targets the Ca2+-regulated isozymes, CKIδ and CKIɛ, we examined the effect of down-regulating these enzymes on Ser-1106 phosphorylation. Down-regulation of these isozymes with targeted si-RNAs led to hypophosphorylation of the Ser-1106 containing peptide. However, si-RNA-mediated down-regulation of CKIIα and α′ did not alter Ser-1106 phosphorylation. Furthermore, reduced phosphorylation of Ser-1106, observed in HRR25 (CKIδ/ɛ homologous gene)-deleted Saccharomyces cerevisiae cells transformed with human topo IIα, was enhanced following expression of human CKIɛ. Down-regulation of CKIδ and CKIɛ also led to reduced formation of etoposide stabilized topo II–DNA cleavable complex. These results provide strong support for an essential role of CKIδ/ɛ in phosphorylating Ser-1106 in human topo IIα and in regulating enzyme function

R parity violating contribution to e+e−(μ+μ−)→tcˉe^+e^-(\mu^+\mu^-)\to t{\bar c}

In this article we consider the contribution of $R_p$ violating couplings to the process $e^+e^-(\mu^+\mu^-)\to t{\bar c}$ at high energy lepton collider. We show that the present upper bound on the relevant $R_p$ violating coulpings obtained from low energy measurements would produce a few hundred to a thousand top-charm events at the next linear $e^+e^-(\mu^+\mu^-)$ collider. Hence, it should be possible to observe the rare process at future lepton collider.Comment: LaTEX, 13 pages, one figure is removed. A brief discussion on possible backgrounds is added. To appear in Phys. Rev.

Flavor changing single top quark production channels at e^+e^- colliders in the effective Lagrangian description

We perform a global analysis of the sensitivity of LEP2 and e^+e^- colliders with a c.m. energy in the range 500 - 2000 GeV to new flavor-changing single top quark production in the effective Lagrangian approach. The processes considered are sensitive to new flavor-changing effective vertices such as Ztc, htc, four-Fermi tcee contact terms as well as a right-handed Wtb coupling. We show that e^+ e^- colliders are most sensitive to the physics responsible for the contact tcee vertices. For example, it is found that the recent data from the 189 GeV LEP2 run can be used to rule out any new flavor physics that can generate these four-Fermi operators up to energy scales of \Lambda > 0.7 - 1.4 TeV, depending on the type of the four-Fermi interaction. We also show that a corresponding limit of \Lambda > 1.3 - 2.5 and \Lambda > 17 - 27 TeV can be reached at the future 200 GeV LEP2 run and a 1000 GeV e^+e^- collider, respectively. We note that these limits are much stronger than the typical limits which can be placed on flavor diagonal four-Fermi couplings. Similar results hold for \mu^+\mu^- colliders and for tu(bar) associated production. Finally we briefly comment on the necessity of measuring all flavor-changing effective vertices as they can be produced by different types of heavy physics.Comment: 34 pages, plain latex, 7 figures embadded in the text using epsfig. Added new references and discussions regarding their relevance to the paper. Added more comments on the comparison between flavor-changing and flavor-diagonal contact terms and on the importance of measuring the Ztc verte

Flavor changing Z-decays from scalar interactions at a Giga-Z Linear Collider

The flavor changing decay Z -> d_I \bar{d}_J is investigated with special emphasis on the b \bar{s} final state. Various models for flavor violation are considered: two Higgs doublet models (2HDM's), supersymmetry (SUSY) with flavor violation in the up and down-type squark mass matrices and SUSY with flavor violation mediated by R-parity-violating interaction. We find that, within the SUSY scenarios for flavor violation, the branching ratio for the decay Z -> b \bar{s} can reach 10^{-6} for large \tan\beta values, while the typical size for this branching ratio in the 2HDM's considered is about two orders of magnitudes smaller at best. Thus, flavor changing SUSY signatures in radiative Z decays such as Z -> b \bar{s} may be accessible to future ``Z factories'' such as a Giga-Z version of the TESLA design.Comment: 27 pages, 15 figures, REVTeX4. A new section added and a few minor corrections were made in the tex

Broken R Parity Contributions to Flavor Changing Rates and CP Asymmetries in Fermion Pair Production at Leptonic Colliders

We examine the effects of the R parity odd renormalizable interactions on flavor changing rates and CP violation asymmetries in the production of fermion-antifermion pairs at $e^-- e^+$ leptonic colliders. The produced fermions may be leptons, down-quarks or up-quarks, and the center of mass energies may range from the Z-boson pole up to $1000$ GeV. Off the Z-boson pole, the flavor changing rates are controlled by tree level amplitudes and the CP asymmetries by interference terms between tree and loop level amplitudes. At the Z-boson pole, both observables involve loop amplitudes. The lepton number violating interactions, associated with the coupling constants, \l_{ijk}, \l'_{ijk}, are only taken into account. The consideration of loop amplitudes is restricted to the photon and Z-boson vertex corrections. We briefly review flavor violation physics at colliders. We present numerical results using a single, species and family independent, mass parameter, $\tilde m$, for all the scalar superpartners and considering simple assumptions for the family dependence of the R parity odd coupling constants.Comment: Latex File. 23 pages. 4 postscript figures. 1 table. Revised version with new results and several corrections in numerical result

Charged Lepton Flavour Violation from Massive Neutrinos in Z Decays

Present evidences for neutrino masses and lepton flavour mixings allow to predict, in the Standard Model with light neutrinos, branching rates for the decays Z --> e mu, mu tau, e tau of less than 10^{-54}, while present experimental exclusion limits from LEP 1 are of order 10^{-5}. The GigaZ option of the TESLA Linear Collider project will extend the sensitivity down to about 10^{-8}. We study in a systematic way some minimal extensions of the Standard Model and show that GigaZ might well be sensitive to the rates predicted from these scenarios.Comment: 24 pages, 4 figures, LaTeX, uses axodraw.st

Lepton flavor violating Z boson decays induced by scalar unparticle

We predict the branching ratios of the lepton flavor violating Z boson decays Z\to e^{\pm} \mu^{\pm}, Z\to e^{\pm} \tau^{\pm} and Z\to \mu^{\pm} \tau^{\pm} in the case that the lepton flavor violation is carried by the scalar unparticle mediation. We observe that their BRs are strongly sensitive to the unparticle scaling dimension and the branching ratios can reach to the values of the order of 10^{-8}, for the heavy lepton flavor case, for the small values of the scaling dimension.Comment: 15 pages, 5 figures, 1 tabl