Clinical relevance of memory performance during Wada is stimulus type dependent

OBJECTIVES: This study aimed to investigate whether different types of memory stimulus provide different information during the Wada or intracarotid amytal procedure (IAP) in patients with refractory medial temporal lobe epilepsy (MTLE). METHODS: Eighty nine surgical candidates with documented MTLE and selected for left hemispheric language dominance underwent memory assessment with verbal and dually encodable stimuli during a presurgical IAP. RESULTS: The overall IAP memory performance with the left hemisphere is significantly better than with the right hemisphere regardless of lesion side. This can be explained by the left hemispheric advantage of encoding all stimuli, whereas the right hemisphere has only limited resources to encode verbal stimuli. More importantly, it appeared that dually encodable items remain more readily recognised following injection ipsilateral to the lesion, whereas verbal items are always better recognised following right hemisphere injection regardless of lesion side. CONCLUSIONS: Verbal IAP stimuli show left hemispheric sensitivity in left language dominant MTLE patients. The dually encodable items of the IAP appear lesion sensitive.     

Mixture design of theophylline retard formulation

Three different cellulose derivatives (hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC) and microcrystalline cellulose (MC)) were used to prepare tablets containing 10% of theophylline with the aid of wet granulation. The retardation effect of different compositions of these cellulose derivatives was investigated. Using mixture design, the formulations with the best retardation properties were selected. On the basis of these results, tablets with different compositions containing 60% (300 mg) of theophylline were prepared. The simulation was performed on a personal computer with the implemented digital simulation language SIMCOS to predict steady-state plasma levels. It was established that formulation C, composed of 34.6% of MC 4.7% of HPMC 0.7% of HPC and 60% of theophylline exhibits in vivo the same retardation effect as commercially available theophylline tablets.     

Grasping soft tissue by means of vacuum technique

IntroductionA notable characteristic of bariatric surgery is the frequent manipulation of the bowel. The bowel is large, delicate, flexible, and has a natural lubricant on the tissue surface. Therefore the bowel is difficult to grasp and manipulate. Vacuum technique is commonly used in industry for all types of grasping and manipulation. Two types of nozzles that differed slightly in geometry (NT1 and NT2), were reviewed in an experimental set up for pull tests on pig bowels.Materials and methodsAn experimental set-up was used to conduct a series of pull tests on pig bowel tissue. The basic principle of the measurements was a Newton's force balance; F_Pmax = Δp × A. Student t-tests, two-way ANOVA and Wilcoxon signed rank tests were conducted for the statistical analysis of NT1 and NT2 with regard to the maximum pull force (F_Pmax).ResultsConcerning NT1 the Newton's force balance could not be confirmed. Concerning NT2 the Newton's force balance could partly be confirmed. For both nozzle types the effect of Δp on F_Pmax was significant. F_Pmax increases linear in proportion as Δp increases. This relation between F_Pmax and Δp was confirmed by the Newton's force balance.DiscussionThe results confirm that vacuum technique can be used as a grasp technique for soft organs, particularly the bowels. By means of a clever design of the nozzle a firm grip can be obtained on the bowel segments. Therefore vacuum technique should be studied for further development of instruments, graspers and retractors, to be used in the abdominal area.     

Physicochemical characterization of protein-loaded pectin-chitosan nanoparticles prepared by polyelectrolyte complexation

Recent advances in nanotechnology applied to proteins are directed towards safer and simpler methods of preparation, using naturally occurring polymers such as alginate, pectin and chitosan. In this study, pectin-chitosan nanoparticles (NPs) were designed by the mild process of polyelectrolyte complexation, which occurs at room temperature without using sonication or organic solvents. NPs with a mean diameter between 300 and 400 nm and 45 to 86% protein association efficiency were obtained by varying the pectin:chitosan mass ratio and initial protein concentration. A prolonged release profile without burst effect of investigated ovalbumin from pectin-chitosan NPs was determined.     

Surgical successes and failures of invasive video-EEG monitoring in the presurgical evaluation of epilepsy

Invasive monitoring with intracranial electrodes continues to play a critical role in the presurgical evaluation of patients with medically intractable epilepsy. Intracranial monitoring helps in localizing the epileptogenic zone and can be used to delineate eloquent cortical areas adjacent to this zone. In this review we analyzed surgical successes and failures of invasive video-electroencephalography (EEG) monitoring. Thorough understanding of all potential complications is of paramount importance not only for detection and successful management of intractable epilepsy but also for medicolegal purposes, as patients and their relatives need to be fully informed about the possible risks associated with invasive monitoring. A mortality rate between 0.5% and 2.8% has been reported. Cerebrospinal fluid (CSF) leaks and infections are the most frequent complications, with an incidence ranging from 0-31.3% and from 0-17.4%, respectively. The incidence of intracranial hemorrhage is reported to be up to 14% with subdural hematomas being the most prevalent. Epidural hematomas are less frequent and encountered in up to 2.6% of cases. Intraparenchymal hematomas are even less frequent and are typically associated with the placement of depth electrodes. In 47-98% of cases, invasive video-EEG monitoring results into resective surgery. Invasive video-EEG monitoring is a reasonably safe and effective method to help delineate the epileptogenic zone and its relation to eloquent cortex.     

Influence of nanosized delivery systems with benzyl nicotinate and penetration enhancers on skin oxygenation

Many novel nanosized delivery systems have been designed for topical application of drugs since they can overcome the skin barrier and improve drug bioavailability. The increased absorption is often a consequence of a reversibly disrupted barrier function of the skin by the vehicle itself or by specific ingredients that act as penetration enhancers. This paper reports the effects of two nanosized systems (microemulsion and liposomes), in the presence and absence of penetration enhancers (PE), on the topical delivery of a lipophilic drug in vivo and compares that to classical hydrogel formulation. A vasodilator benzyl nicotinate (BN), which increases the blood flow of the skin, was incorporated into the formulations, and skin oxygenation was followed by electron paramagnetic resonance oximetry. It was found that microemulsions and liposomes (with or without PE) accelerate the rate of BN action when compared to hydrogel. However, incorporation of PE in microemulsion also improves the effectiveness of BN action. To understand why PE enhances the action of BN, its effect on the structure of the stratum corneum was investigated in vitro. The increased fluidity of the stratum corneum lipids provides an explanation for the greater penetration of BN into the skin when the drug and PE are together incorporated into the appropriate formulation.     

Calcipotriol Affects Keratinocyte Proliferation by Decreasing Expression of Early Growth Response-1 and Polo-like Kinase-2

Purpose Calcipotriol is a potent drug for topical treatment of psoriasis because it manages to inhibit keratinocyte proliferation. In the present study we investigated the effects of calcipotriol on gene expression in human keratinocytes in terms of mechanism of how calcipotriol decreases proliferation. Materials and methods Cell proliferation was analyzed by MTT assay. The differential display approach together with qPCR was used to assess the gene expression after treatment. In addition, Western immunoblotting revealed differences on the protein level. Finally, transfection of the KCs with specific small interfering RNA determined the genes necessary to inhibit proliferation. Results KCs proliferation was decreased in a concentration-dependent manner. Moreover, calcipotriol dowregulated the expression of two proliferation factors: early growth response-1 (EGR1) and polo-like kinase-2 (PLK2). The protein levels of EGR1 and PLK2 were also decreased. Specific siRNA against EGR1 and PLK2 in KCs resulted in marked reduction of EGR1 and PLK2 expression. In both cases, the reduction resolved in the decreased proliferation of KCs. Conclusion This study provides a new insight into how calcipotriol affects proliferation of keratinocytes by decreasing the expression of EGR1 and PLK2. Furthermore, the results offer groundwork for developing novel compounds for the treatment of hiperproliferative skin disorders like psoriasis.     

Surface active stabilizer tyloxapol in colloidal dispersions exerts cytostatic effects and apoptotic dismissal of cells

Solid lipid nanoparticles (SLN) have been praised for their advantageous drug delivery properties such as biocompatibility, controlled release and passive drug targeting. However, the cytotoxicity of SLN and their ingredients, especially over a longer time period, has not been investigated in detail. We examined the critical issues regarding the use of a surface active stabilizer Tyloxapol (Tyl) for the preparation of solid lipid particles (SLP) and their effects on cellular functions and viability.SLP composed of behenate, phospholipids and a stabilizer, Tyloxapol or Lutrol (Lut), were prepared by the lipid melt method, labeled with a fluorescent dye and tested on Jurkat or HEK293 cells. The nano-sized particles were rapidly internalized and exhibited cytoplasmic localization. Incubation of cells with SLP-Tyl resulted in a dose- and time-dependent cytostatic effect, and also caused moderate and delayed cytotoxicity. Tyloxapol solution or SLP-Tyl dispersion caused the detachment of HEK293 cells, a decrease in cell proliferation and alterations in cellular morphology. Cell cycle analysis revealed that, while the unfavourable effects of SLP-Tyl and Tyloxapol solution are similar initially, longer incubation results in partial recovery of cells incubated with the dispersion of SLP-Tyl, whereas the presence of Tyloxapol solution induces apoptotic cell death. These findings indicate that Tyloxapol is an unfavourable stabilizer of SLP used for intracellular delivery and reinforce the role of stabilizers in a design of SLP with minimal cytotoxic properties.     

Continuous local intrahippocampal delivery of adenosine reduces seizure frequency in rats with spontaneous seizures

Purpose: Despite different treatment options for patients with refractory epilepsy such as epilepsy surgery and neurostimulation, many patients still have seizures and/or drug‐related cerebral and systemic side effects. Local intracerebral delivery of antiepileptic compounds may represent a novel strategy with specific advantages such as the option of higher local doses and reduced side effects. In this study we evaluate the antiepileptic effect of local delivery of adenosine in the kainic acid rat model, a validated model for temporal lobe epilepsy. Methods: Fifteen rats, in which intraperitoneal kainic acid injection had induced spontaneous seizures, were implanted with a combination of depth electrodes and a cannula in both hippocampi. Cannulas were connected to osmotic minipumps to allow continuous hippocampal delivery. Rats were freely moving and permanently monitored by video‐EEG (electroencephalography). Seizures were scored during 2 weeks of local hippocampal delivery of saline (baseline), followed by 2 weeks of local adenosine (6 mg/ml) (n = 10) or saline (n = 5) delivery (0.23 μl/h) (treatment). In 7 of 10 adenosine‐treated rats, saline was also delivered during a washout period. Results: During the treatment period a mean daily seizure frequency reduction of 33% compared to the baseline rate was found in adenosine‐treated rats (p < 0.01). Four rats had a seizure frequency reduction of at least 50%. Both nonconvulsive and convulsive seizures significantly decreased during the treatment period. In the saline‐control group, mean daily seizure frequency increased with 35% during the treatment period. Conclusions: This study demonstrates the antiseizure effect of continuous adenosine delivery in the hippocampi in rats with spontaneous seizures.