Reduction of rapid eye movement sleep by diurnal and nocturnal seizures in temporal lobe epilepsy

BACKGROUND: Patients with brief, complex partial seizures frequently suffer from tiredness and decreased productivity that continue well beyond the postictal period. A possible explanation is that seizures, even when occurring during the day, disrupt sleep the following night. OBJECTIVE: To determine the effect of temporal lobe complex partial seizures on sleep structure and daytime drowsiness. METHODS: Patients with temporal lobe epilepsy were admitted for video-electroencephalography monitoring. All-night polysomnography was recorded under the following 3 conditions: seizure free, seizure during the day before the recording, and seizure during the recording. Percentage of time in each sleep stage, sleep efficiency, and time to first and second rapid eye movement (REM) period were compared for seizure vs control conditions. Daytime drowsiness was also measured, using a modified maintenance of wakefulness test and 2 subjective drowsiness tests. RESULTS: Daytime seizures reduced REM from 18%+/-1% to 12%+/-2% (P = .003). Night seizures reduced REM from 16%+/-1% to 6.8%+/-2% (P<.001). Night seizures also significantly reduced stages 2 and 4 while increasing stage 1 sleep. Night seizures, but not day seizures, significantly reduced sleep efficiency, increased time to first REM period, and increased drowsiness as measured by the maintenance of wakefulness test. CONCLUSIONS: Temporal lobe complex partial seizures decrease REM sleep, particularly when occurring during sleep but also when occurring on the previous day. This may, in part, be responsible for the prolonged impairment of functioning that some patients report following seizures.     

Naked DNA vaccination differentially modulates autoimmune responses in experimental autoimmune encephalomyelitis

Vaccination with naked DNA represents a therapeutic strategy currently under consideration in multiple sclerosis (MS). In this study, we tested the potential therapeutic effect of vaccination with a naked DNA construct encoding proteolipid protein (pRc/CMV-PLP) upon the outcome of subsequent sensitization for experimental autoimmune encephalomyelitis (EAE) actively-induced in SJL mice with PLP139-151 peptide in adjuvant. Intramuscular vaccination with the naked DNA pRc/CMV-PLP construct led to PLP expression in local muscle tissue that persisted for about 8 weeks. Early sensitization for EAE (4 weeks after DNA vaccination) caused recipient mice to develop a severe, exacerbated form of disease (in comparison to control mice), while late sensitization (>10 weeks) resulted in a milder, ameliorated form. In the groups sensitized <10 weeks post-DNA vaccination with pRc/CMV-PLP induction of a Th1-type cytokine response was noted. In contrast, sensitization >10 weeks post-DNA vaccination led to peripheral tolerance as evidenced by a decrease in T cell proliferation and cytotoxic T cell response, no Th2 response, and no increase in apoptosis. These data are novel in that they demonstrate a differential effect of DNA vaccination and have important implications for its use as a mechanism to enhance or modulate immune reactivity.     

Tailoring width of microfabricated nanochannels to solute size can be used to control diffusion kinetics.

Top-down microfabrication techniques were used to create silicon-based membranes consisting of arrays of uniform channels having a width as small as 7 nm. The measurement of diffusion kinetics of solutes across these membranes under sink conditions reveals non-Fickian behavior as the nanopore width approaches the hydrodynamic diameter of the solute. Zero-order diffusion of interferon is observed at channel width of 20 nm, and the same phenomenon occurs with albumin and 13-nm-wide channels, whereas Fickian diffusion kinetics is seen at 26 nm and larger pore sizes. A prototypical drug delivery device is described that is fitted with a 13-nm nanopore membrane and loaded with radio-labeled BSA. Following subcutaneous implantation in rats, diffusion from the device provided prolonged levels of BSA in the blood. Such a nonmechanical device offers important advantages in drug delivery applications, including zero-order release and high loading capacity.     

Clinical trials in relapsing-remitting multiple sclerosis /a new proposal for dealing with basic problems and restrictions

The natural course of multiple sclerosis is characterized by a high variability of pattern, relapse rate and different progression indices. They also present a dramatic impact on the interpretation of treatment trials. Reports, based on uncontrolled observations are therefore of little value. Currently it is generally accepted that a proper treatment trial should be double blinded and, although probably controversial, that it should be compared with a group of MS patients treated with placebo. Currently MS is considered as a generalized degenerative disease. The lesions are persistent, which is the reason why immunomodulatory treatment has to be started as early as possible. An alternative approach, somewhat suggestive for the use of placebo trials, seems to be a comparison of proposed new drug therapy group with a group of patients treated with a generally accepted reference drug.     

Near-infrared spectroscopy in evaluation of cerebral oxygenation during vasovagal syncope

Near-infrared spectroscopy (NIRS) offers a non-invasive, real-time monitoring of cerebral oxygenation. This method is based on the oxygenation and the light wavelength dependent absorption of near-infrared light by tissue chromophores, e.g. oxyhaemoglobin and deoxyhaemoglobin. The objective of the present study was the application of NIRS for evaluation of the brain function during vasovagal syncope (VVS). The VVS is a clinical syndrome affecting ca 3.5% of the population and for which the widely used diagnostic examination in this disease entity is the head-up tilt table test (HUT). In this study 69 patients with a history of VVS were examined using HUT. In 42 patients VVS was provoked. Results of the examination have shown that the changes in cerebral oxygenation measured by the NIRS technique are distinctly visible before the syncope. A gradual decrease of oxyhaemoglobin followed by its sudden drop was observed in all the VVS patients. Changes in the oxyhaemoglobin concentration measured by NIRS were observed on average 3.3 min before the syncope. They preceded the presyncope symptoms about 1.3 min (p < 0.005), the blood pressure and heart rate drop 2.2 min (p < 0.0001) and the arterial blood saturation 2.6 min (p < 0.00001).     

The influence of SiO2 and SiO2–TiO2 intermediate coatings on bond strength of titanium and Ti6Al4V alloy to dental porcelain

ObjectivesThe purpose of this study was to evaluate the bond strength of commercially pure CPTi and Ti6Al4V alloy with SiO₂ and SiO₂–TiO₂ intermediate coatings to Triceram low-fusing dental porcelain.MethodsThe multilayered systems were characterized from the standpoint of microstructure analysis (SEM), the mode of failure, the nature of bonding and the influence of intermediate coatings on the improvement of bond strength. The SiO₂ and SiO₂–TiO₂ intermediate coatings were applied on the substrate materials by the sol–gel dipping technique. The metal–ceramic bond strength was investigated according to ISO 9693 standards using the three-point flexure bond test.ResultsStatistically significant higher bond strength of the metal–porcelain for Ti6A14V alloy (28.24 MPa), Ti6Al4V/SiO₂ (32.17 MPa) and Ti6Al4V/SiO₂–TiO₂ (36.09 MPa) was noted in comparison to CPTi (23.04 MPa), CPTi/SiO₂ (27.98 MPa) and CPTi/SiO₂–TiO₂ (28.84 MPa), respectively. The nature of metal-intermediate coating–porcelain bonding was both mechanical and chemical. The failure in all systems was cohesive and adhesive, mainly adhesive.SignificanceThe application of SiO₂ and SiO₂–TiO₂ intermediate coatings, produced by the sol–gel method, to both CPTi and Ti6Al4V alloy significantly improves the bond strength of metal–porcelain systems in comparison to the metal substrate only after sandblasting, and may have clinical use.     

Targeting the function of mature dendritic cells by human cytomegalovirus: a multilayered viral defense strategy.

Human cytomegalovirus (HCMV) can suppress and evade the immune system. We have identified as a mechanism the ability of HCMV to infect dendritic cells (DC), which initiate the antiviral immune response. HCMV-infected DC show enhanced expression of costimulatory molecules. In contrast, MHC molecules are partially downregulated, leading to a reduced antigen-presenting capacity. Moreover, the apoptosis-inducing ligands CD95L (FasL) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are upregulated, thereby enabling HCMV-infected DC to delete activated T lymphocytes. This additional layer of viral defense is complemented by nondeletional mechanisms, which suppress surviving T cells. Thus, infection of DC allows the virus to blunt the antiviral T cell response by a multilayered defense strategy and could play a pivotal role in HCMV-triggered immunosuppression.