Modulation of neural cell membrane conductance by the herbal anxiolytic and antiepileptic drug aswal

To evaluate the effects of aswal on ionic fluxes and neuronal excitation, we performed extracellular and whole cell patch clamp recordings on CA1 pyramidal neurons of guinea pigs and Long-Evans rats. Aswal (100-250 mg/l) was administered systemically, and its effects on the rate of synchronized extracellular field potentials (EFP), membrane parameters, action potentials and postsynaptic potentials were recorded. The extracellular results obtained are consistent with calcium antagonistic properties. Intracellular recordings suggest that a direct sodium antagonistic effect as seen in many antiepileptic drugs plays no significant role. Further effects on ligand gated ion channels are discussed controversially. In summary, the cellular action of aswal appears heterogeneous with calcium antagonism playing a prominent role in counteracting excitation which may be a common feature in epilepsy and different psychiatric conditions as mood and anxiety disorder. Copyright (C) 2000 S. Karger AG, Basel

New insights into the mechanisms and sites of action of lamotrigine

This study was aimed at investigating the effects of lamotrigine (LTG) on electrically evoked field excitatory postsynaptic potentials (fEPSP) and population spikes in the CA1 hippocampal region of guinea pigs. The concentration response curves showed different actions of LTG on fEPSP and on population spikes. The data are in contrast to previous findings that suggest the drug acts primarily on presynaptic sites via a blockade of the release of excitatory amino acids, In the range of therapeutic plasma levels, synaptic transmission was not affected. Copyright (C) 2000 S. Karger AG, Basel

Differential treatment of bipolar disorder with old and new antiepileptic drugs

Although lithium remains the preferred medication for bipolar disorders, new investigations suggest that only 60 to 80% of patients have a good response with a classical presentation. The antiepileptics carbamazepine and valproate are important alternatives. Several studies have shown that lithium, carbamazepine and valproate are effective in pure mania. Mixed mania and rapid cycling respond, however, well to valproate. One disadvantage of carbamazepine is its enzyme inducing property with the consequence of a decrease of plasma levels of other psychotropic medications and a worsening of psychopathology. First data indicate a good antimanic and antidepressive efficacy of the new antiepileptic drug lamotrigine

Expression des "activated leukocyte cell adhesion molecule" im Mammakarzinom: Prädiktivität für das Ansprechen auf eine taxanfreie Chemotherapie

Zusammenfassung: Ziele: "Activated leukocyte cell adhesion molecule" (ALCAM) ist ein Oberflächenimmunglobulin und wird in vielen Mammakarzinomen exprimiert. Es wird vermutet, dass ALCAM in der Tumorgenese und -progression eine Rolle spielt. Die Bedeutung des Adhäsionsmoleküls ALCAM für das Ansprechen auf eine taxanfreie adjuvante Chemotherapie wurde untersucht. Material und Methoden: Gewebeproben von 162Patientinnen mit Mammakarzinomen wurden im Hinblick auf die Expression des ALCAM-Proteins untersucht. Immunhistologische Untersuchungen (IHC) und Western-Blot-Analysen (WB) wurden mit einem monoklonalen Antikörper gegen ALCAM durchgeführt. Die Proteinmengen im WB wurden densitometrisch quantifiziert und mit klinischen sowie histologischen Parametern korreliert. Die Ergebnisse wurden auf mRNA-Ebene mithilfe der Microarray-Analysen (Affymetrix) validiert. Ergebnisse: In der normalen Brustdrüse wird ALCAM in den luminalen und den basalen Epithelzellen exprimiert. Die WB-Analysen von Mammakarzinomen zeigen eine positive Korrelation der ALCAM-Expression mit dem Östrogenrezeptorstatus (p=0,04). Bei Patientinnen, die eine taxanfreie Chemotherapie erhalten haben, ist eine hohe ALCAM-Expression (WB, Affymetrix) prädikitiv für das Ansprechen einer Chemotherapie. Der mediane mRNA-Level von ALCAM war bei Patientinnen, die während des Beobachtungszeitraums noch lebten, 4,5-fach höher als bei Patientinnen, die verstarben. Schlussfolgerung: Ein hoher ALCAM-Gehalt korreliert positiv mit dem Östrogenrezeptorstatus. Außerdem ist ALCAM ein prädiktiver Faktor für das Ansprechen einer taxanfreien Chemotherapi

Book Review of Grandparents Raising Grandchildren: Coping with Addiction By Andrea Smith, PhD and Linda Dannison, PhD

Book Review of Grandparents Raising Grandchildren: Coping with Addiction By Andrea Smith, PhD and Linda Dannison, Ph

Approaches to the Different Levels of Consumer Protection in European Contract law, focusing on Food Safety Regulations

In the area of contract law an important aspect is consumer protection, on the national and European level, which involves cross border elements. Within the European Union Directives and Regulations secure a minimum level of protection for the consumer. These laws are designed to prevent business to gain by fraud or unfair practices; they protect the weaker party, the consumer, from the stronger party, the businesses. In Article 2 (B) of Directive 93/13/EEC on unfair terms in consumer contracts, a consumer is defined as “any natural person who, is acting for purposes which are outside his business, trade or profession.” To achieve the optimal level of consumer protection within the EU, in order for the internal market to work properly; the aim of this paper is to address the following research question: “How to approach the differences in level of Consumer protection, in a civil law country compared to a country under the common law regime?”. In order to be able to outline some of the differences the issue of food safety will be used as a case-study

Book Review of Grandparents Raising Grandchildren: Expanding Your View

N/A for book revie

Examining Fifth-Grade In-School Physical Activity Patterns and How Many Days of Monitoring are Needed

PURPOSE: The purpose of the study was to examine in-school physical activity patterns among fifth-grade students residing in a Midwestern community. Variables observed were minutes of vigorous + activity, vigorous activity, moderate activity, easy activity and very easy activity along with steps and calories expended. A secondary purpose of this study was to determine the minimum number of days necessary to estimate mean physical activity levels, as both moderate-to-vigorous physical activity (MVPA) and steps per day, in fifth-grade students using objective physical activity monitors across two semesters. METHODS: Activity patterns were assessed during two school semesters, spring (N = 82 boys & 84 girls) and fall (N = 89 boys & 91 girls), from 10-12 year old fifth-grade students in four Midwestern elementary schools. Data was collected using wrist worn activity trackers. The devices were administered by teachers at the start of each school day and collected at the end of each school day for two consecutive weeks. Monitors measured MVPA and steps per day. Demographic and anthropometric data were also recorded (age, height, weight). All data was uploaded to the device website database and then collected by the primary researcher. Physical activity measures were surveyed and compared across the four different schools, semesters and genders. In the secondary analysis, steps and MVPA were examined, individually, with Cronbach’s alpha to determine how many days of measurement were needed to assess mean activity patterns. RESULTS: Average in-school MVPA for boys in the fall semester accounted for 79.17% of the daily recommendation (47.5 of the 60 minutes), for girls, in-school MVPA accounted for 69.14% of the daily recommendation (41.49 of the 60 minutes). During the spring semester, boys attained 74.39% or 44.64 minutes of their MVPA in-school, while girls attained 60.46% or 36.27 minutes of their MVPA in-school. Average steps measured in-school during the fall semester was 7,491 or 57% of total daily recommendation, average steps measured during the spring semester was 7,006 or 54% of the daily recommendation. The reliability analysis suggested that at least four days of measurement were needed to achieve an alpha of 0.80 for both steps (α = 0.825, 95% CI [0.777-0.865]) and MVPA (α = 0.839, 95% CI [0.795-0.87]) during spring collection. During the fall semester, at least four days were also necessary to achieve a reliability of 0.80 in steps (α = 0.803, 95% CI [0.751-0.846]) and MVPA (α = 0.811, 95% CI [0.761-0.852]). However, fall five-day activity patterns did exhibit greater variability than four-day activity patterns in both steps (α = 0.784, 95% CI [0.730-0.830]) and MVPA (α = 0.794, 95% CI [0.742-0.838]). CONCLUSIONS: Our results show that boys attained more steps and minutes of MVPA during both semesters of collection than girls. Both reached promising levels of activity in-school, allowing them optimal opportunity out of school to reach daily activity goals. These results also indicate that four-day activity monitoring protocols most accurately estimate the mean in-school physical activity patterns, steps and MVPA, in fifth grades students. It should be noted that the results indicate consistency was not improved by a fifth day of measurement in steps and MVPA during a five-day collection period

Analysis of hyperekplexia mutations identifies transmembrane domain rearrangements that mediate glycine receptor activation

Pentameric ligand-gated ion channels (pLGICs) mediate numerous physiological processes and are therapeutic targets for a wide range of clinical indications. Elucidating the structural differences between their closed and open states may help in designing improved drugs that bias receptors toward the desired conformational state. We recently showed that two new hyperekplexia mutations, Q226E and V280M, induced spontaneous activity in α1 glycine receptors. Gln-226, located near the top of transmembrane (TM) 1, is closely apposed to Arg-271 at the top of TM2 in the neighboring subunit. Using mutant cycle analysis, we inferred that Q226E induces activation via an enhanced electrostatic attraction to Arg-271. This would tilt the top of TM2 toward TM1 and hence away from the pore axis to open the channel. We also concluded that the increased side chain volume of V280M, in the TM2-TM3 loop, exerts a steric repulsion against Ile-225 at the top of TM1 in the neighboring subunit. We infer that this steric repulsion would tilt the top of TM3 radially outwards against the stationary TM1 and thus provide space for TM2 to relax away from the pore axis to create an open channel. Because the transmembrane domain movements inferred from this functional analysis are consistent with the structural differences evident in the x-ray atomic structures of closed and open state bacterial pLGICs, we propyose that the model of pLGIC activation as outlined here may be broadly applicable across the eukaryotic pLGIC receptor family