329 research outputs found
Efficacy, safety, and potential of extended-release lamotrigine in the treatment of epileptic patients
Epilepsy is a frequent, chronic disease demanding long-term medication with antiepileptic drugs (AEDs). When slow release formulations of AEDs are used the chance of compliance and control of seizures is increased. Lamotrigine (LTG) is a broad spectrum antiepileptic drug (AED), effective against both generalized and partial seizures. Its immediate-release formulation (LTG-IR) requires twice-daily dosing. In contrast, an extended-release formulation (LTG-XR) may be given once daily, providing a flatter dose-concentration curve with apparently lower maximum serum levels. Simplified dosing positively affects compliance and LTG-XR has a similar profile of efficacy and tolerability to LTG-IR. Rashes, including Stevens–Johnson syndrome, are the most serious adverse effect impacting 0.8% of pediatric patients. Thus, LTG-XR should be discontinued upon the appearance of rash
Clinical utility of adjunctive retigabine in partial onset seizures in adults
In ~30% of epileptic patients, full seizure control is not possible, which is why the search for novel antiepileptic drugs continues. Retigabine exhibits a mechanism of action that is not shared by the available antiepileptic drugs. This antiepileptic enhances potassium currents via Kv7.2–7.3 channels, which very likely results from destabilization of a closed conformation or stabilization of the open conformation of the channels. Generally, the pharmacokinetics of retigabine are linear and the drug undergoes glucuronidation and acetylation. Results from clinical trials indicate that, in the form of an add-on therapy, retigabine proves an effective drug in refractory epileptic patients. The major adverse effects of the add-on treatment are dizziness, somnolence, and fatigue. This epileptic drug is also considered for other conditions – neuropathic pain, affective disorders, stroke, or even Alzheimer’s disease
Pharmacological and non-pharmacological approaches to life threatening conditions in epilepsy
Cauchy's infinitesimals, his sum theorem, and foundational paradigms
Cauchy's sum theorem is a prototype of what is today a basic result on the
convergence of a series of functions in undergraduate analysis. We seek to
interpret Cauchy's proof, and discuss the related epistemological questions
involved in comparing distinct interpretive paradigms. Cauchy's proof is often
interpreted in the modern framework of a Weierstrassian paradigm. We analyze
Cauchy's proof closely and show that it finds closer proxies in a different
modern framework.
Keywords: Cauchy's infinitesimal; sum theorem; quantifier alternation;
uniform convergence; foundational paradigms.Comment: 42 pages; to appear in Foundations of Scienc
Aegilops-Secale amphiploids: chromosome categorisation, pollen viability and identification of fungal disease resistance genes
The aim of this study was to assess the potential breeding value of goatgrass-rye amphiploids, which we are using as a “bridge” in a transfer of Aegilops chromatin (containing, e.g. leaf rust resistance genes) into triticale. We analysed the chromosomal constitution (by genomic in situ hybridisation, GISH), fertility (by pollen viability tests) and the presence of leaf rust and eyespot resistance genes (by molecular and endopeptidase assays) in a collection of 6× and 4× amphiploids originating from crosses between five Aegilops species and Secale cereale. In the five hexaploid amphiploids Aegilops kotschyi × Secale cereale (genome UUSSRR), Ae. variabilis × S. cereale (UUSSRR), Ae. biuncialis × S. cereale (UUMMRR; two lines) and Ae. ovata × S. cereale (UUMMRR), 28 Aegilops chromosomes were recognised, while in the Ae. tauschii × S. cereale amphiploid (4×; DDRR), only 14 such chromosomes were identified. In the materials, the number of rye chromosomes varied from 14 to 16. In one line of Ae. ovata × S. cereale, the U-R translocation was found. Pollen viability varied from 24.4 to 75.4%. The leaf rust resistance genes Lr22, Lr39 and Lr41 were identified in Ae. tauschii and the 4× amphiploid Ae. tauschii × S. cereale. For the first time, the leaf rust resistance gene Lr37 was found in Ae. kotschyi, Ae. ovata, Ae. biuncialis and amphiploids derived from those parental species. No eyespot resistance gene Pch1 was found in the amphiploids
A study to evaluate the prevalence and determinants of stress coping strategies in heart failure patients in Poland (CAPS-LOCK-HF sub-study)
"Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma "en coup de sabre" with CNS tumor
Ten Misconceptions from the History of Analysis and Their Debunking
The widespread idea that infinitesimals were "eliminated" by the "great
triumvirate" of Cantor, Dedekind, and Weierstrass is refuted by an
uninterrupted chain of work on infinitesimal-enriched number systems. The
elimination claim is an oversimplification created by triumvirate followers,
who tend to view the history of analysis as a pre-ordained march toward the
radiant future of Weierstrassian epsilontics. In the present text, we document
distortions of the history of analysis stemming from the triumvirate ideology
of ontological minimalism, which identified the continuum with a single number
system. Such anachronistic distortions characterize the received interpretation
of Stevin, Leibniz, d'Alembert, Cauchy, and others.Comment: 46 pages, 4 figures; Foundations of Science (2012). arXiv admin note:
text overlap with arXiv:1108.2885 and arXiv:1110.545
Gene and protein expression of glucose transporter 1 and glucose transporter 3 in human laryngeal cancer—the relationship with regulatory hypoxia-inducible factor-1α expression, tumor invasiveness, and patient prognosis
Increased glucose uptake mediated by glucose
transporters and reliance on glycolysis are common features
of malignant cells. Hypoxia-inducible factor-1α supports the
adaptation of hypoxic cells by inducing genes related to
glucose metabolism. The contribution of glucose transporter
(GLUT) and hypoxia-inducible factor-1α (HIF-1α) activity to
tumor behavior and their prognostic value in head and neck
cancers remains unclear. The aim of this study was to examine
the predictive value of GLUT1, GLUT3, and HIF-1α messenger
RNA (mRNA)/protein expression as markers of tumor
aggressiveness and prognosis in laryngeal cancer. The level of
hypoxia/metabolic marker genes was determined in 106 squamous
cell laryngeal cancer (SCC) and 73 noncancerous
matched mucosa (NCM) controls using quantitative realtime
PCR. The related protein levels were analyzed by
Western blot. Positive expression of SLC2A1, SLC2A3, and
HIF-1α genes was noted in 83.9, 82.1, and 71.7 % of SCC
specimens and in 34.4, 59.4, and 62.5 % of laryngeal cancer
samples. Higher levels of mRNA/protein for GLUT1 and
HIF-1α were noted in SCC compared to NCM (p<0.05).
SLC2A1 was found to have a positive relationship with grade,
tumor front grading (TFG) score, and depth and mode of
invasion (p<0.05). SLC2A3 was related to grade and invasion
type (p<0.05). There were also relationships of HIF-1α with
pTNM, TFG scale, invasion depth and mode, tumor recurrences,
and overall survival (p<0.05). In addition, more advanced
tumors were found to be more likely to demonstrate
positive expression of these proteins. In conclusion, the
hypoxia/metabolic markers studied could be used as molecular
markers of tumor invasiveness in laryngeal cancer.This work was supported, in part, by the statutory
fund of the Department of Cytobiochemistry, University of Łódź, Poland
(506/811), and by grant fromtheNational Science Council, Poland (N403
043 32/2326)
7. Biological Effectiveness of 12 C and 20 Ne Ions with Very High LET
Knowledge of radiobiological effects of heavy ions at the cellular and molecular level is of fundamental importance in the field of radiation therapy (for example C ions) and space radiation biology (for example Ne ions). One of the issues that require deeper investigations is a determination of RBE values for a wide range of LET, for all relevant doses, for many cell types and various kinds of radiations During recent years, the biological effectiveness of heavy ions has been widely investigated with the aim to identify physical characteristics relevant to biological actions. These investigations are pertinent to the use of heavy ions in radiosurgery and radiotherapy. What has not been investigated so thoroughly is the biological effectiveness of heavy ions at low energies and very high LET values. The LET, which is equal to the stopping power of heavy particles, increases sharply at the end of the particle's path, forming a so-called Bragg peak. The shape of the Bragg peak depends on the particle type. Because overlying beams with different energies and components of primary and secondary particles are used in radiotherapy, the knowledge of RBE values of very high LET radiation need to be well characterized. An experimental set-up designed for such investigations was constructed at the isochronic cyclotron in Heavy Ion Laboratory. A more detailed description of the set-up can be found in Ref. CHO-K1 cells have been used as a suitable biological system for our studies. The cell line is characterized by genetic stability, the ability to form colonies, a relatively rapid growth rate with a cell cycle of 12-14 hours. For exposure to ions the cells were seeded in specially designed Petri dishes, which were filled with medium, sealed by a parafilm cover and placed in a vertical sample holder mounted in an x-y-z table that was connected to a special stepping motor. The irradiated sample moved under the beam according to a planned route. Movement was initiated when the number of counts detected by the 20 o particle detector reached the preset value. When all fields have been exposed the sample holder returned to the start position. Stored information enabled to evaluate the beam stability and intensity. The whole set-up was surveyed by a digital camera. The total time of exposure per dish was between 1-5 min. depending on the dose and beam intensity. The dose rates were changed from 0.05 Gy/min. to 1 Gy/min depending on the dose. Cell survival was estimated according to standard procedure
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