Does menopause affect the epilepsy?

Hormonal fluctuations in the menstrual cycle have been shown to have an impact on the epilepsy in women with catamenial epilepsy. The epilepsy frequency is higher in the elderly, and this part of the population is steadily increasing. It is therefore of interest whether the hormonal changes in the menopausal transition affects the epilepsy. The perimenopause is associated with hormonal fluctuations and may worsen the epilepsy in women with catamenial epilepsy. It has been suggested that seizures may improve after menopause, particularly in the women with catamenial epilepsy. There is still however, limited data on the effects of menopause on the epilepsy. Prospective studies imply a long time span, and research in this field is scarce. More research on the relationship between hormonal fluctuations and seizures may enable us to predict the effect on the epilepsy. Special awareness should be given to a woman with epilepsy in the menopausal transition.     

Molecular adsorbent recirculating system in patients with early allograft dysfunction after liver transplantation: a pilot study.

Early allograft dysfunction (EAD) after orthotopic liver transplantation (OLT) causes marked morbidity and mortality. We conducted a prospective pilot study to assess the safety and efficacy of molecular adsorbent recirculating system (MARS) in treatment of EAD after OLT. Twelve consecutive adult liver allograft recipients with a median age of 48 years, 9 of whom were male, were prospectively included and supported with MARS. EAD was defined as the presence of at least 2 of the following: serum bilirubin >10 mg/dL, prothrombin time <40%, aspartate aminotransferase or alanine transferase >1,000 U/L, and plasma disappearance rate of indocyanine green (PDR(ICG)) <10% per minute within 72 hours after reperfusion. One-year patient and graft survival was 66%. There was a significant decrease in serum bilirubin (P = 0.002), serum creatinine (P = 0.006), and aspartate aminotransferase (P = 0.005) and a significant increase in PDR(ICG) (P = 0.007) after MARS treatment. Prothrombin time, albumin level, and platelet count remained stable. Sustained improvement of renal and neurological function and of mean arterial pressure were observed. No MARS-related adverse effects occurred. MARS treatment provides a safe approach to the treatment of EAD after OLT. On the basis of this pilot study, a multicenter randomized clinical trial that uses MARS treatment in EAD after OLT has been initiated.     

On sex/gender related similarities and differences in fMRI language research

Again and again, attempts have been made to find correlates of sex/gender differences in the human brain. Despite the insistence with which differences have been stated, empirical results have not been unequivocal: evidence for and against the influence of sex in the makeup of men's and women's brains has been presented. This article focuses on the relevance of sex/gender related differences in fMRI research, especially with regard to language processing. By discussing some crucial criteria from fMRI examinations, we demonstrate the existence of paradigmatic, methodological and statistical defaults that interfere with assessing the presence or absence of sex/gender differences. These criteria are, among others, the use of contrast analyses, the function of the variable sex/gender as a co-item and the “publication bias”. It is argued that dealing with the sex/gender variable will, at least to some degree, inevitably lead to the detection of differences rather than to the detection of similarities.     

Establishment and validation of an ex vivo human cervical tissue model for local delivery studies.

The objective of this study was to establish and validate an ex vivo human cervical tissue model appropriate for transport studies of molecular and especially nucleic acid based drugs. For that purpose conditions had to be established for a standardized tissue handling and preparation following hysterectomy to allow an immediate experimental use of fresh tissue samples. Samples of the ectocervical, endocervical and the transition zone representing the entire cervix organ were characterized in Franz diffusion cells by the determination of the in vitro permeation of low and high molecular weight markers (propanolol, mannitol, dextran 4000, 10,000, 20,000 and 40,000Da). Additionally, the permeability of mannitol and dextran 4000 across fresh and frozen cervical tissue was compared. The apparent permeability coefficients (P(app)) of the various markers demonstrated (i) that with increasing molecular weight the marker permeability decreases, (ii) an upper permeability limit between 10,000 and 20,000Da, (iii) no significant difference of the permeability across the three cervical tissue zones, (iv) a statistically significant but effectively small variation of the permeability among different patient samples. A continuous difference of approximately two log values between the P(app) values of mannitol and dextran 4000 makes them suitable as an internal marker control pair for each biopsy. Moreover, the P(app) values of both markers across fresh and frozen tissue are comparable. According to the presented data we conclude that the human cervical tissue model has been well characterized and is therefore suitable for local delivery and permeation studies.     

Photodynamic Therapy in Dermatology – an Update 2008

Photodynamic therapy (PDT) is used for the prevention and treatment of non‐melanoma skin cancer. Until recently, clinically approved indications have been restricted to actinic keratoses, nodular and superficial basal cell carcinoma, and – since 2006 – Bowen disease. However, the range of indications has been expanding continuously. PDT is also used for the treatment of non‐malignant conditions such as acne vulgaris and leishmaniasis, as well as for treating premature skin aging due to sun exposure. Here, PDT is used for the stimulation of immunomodulatory effects in contrast to the induction of necrosis and apoptosis as produced in the treatment of skin tumors. The porphyrin precursor 5‐aminolevulinic acid (ALA) or its methyl ester (MAL, so far the only approved formulation in Europe) is applied topically as photosensitizer to exclude systemic reactions. Possible light sources include lasers as well as incoherent light sources; irradiation with incoherent light sources is cheaper and more appropriate for large treatment areas. The main advantages of PDT in comparison to other treatment modalities are its excellent cosmetic results and its high remission rates despite low invasiveness.This article provides up‐to‐date information about PDT with focus on recently published studies.     

Endogenous brain protection by granulocyte-colony stimulating factor after ischemic stroke

Several lines of evidence have demonstrated beneficial effects of the hematopoietic factor G-CSF in experimental stroke. A conclusive demonstration of this effect in G-CSF deficient mice is, however, lacking. We therefore investigated the effect of G-CSF deficiency on infarct volumes, functional recovery, mRNA and protein expression of the matrix metalloproteinase 9 (MMP-9) after stroke. Furthermore we tested the efficacy of G-CSF substitution in G-CSF deficient animals to prevent the potential consequences of G-CSF deficiency. In the present study experimental stroke was induced in female non-treated wildtype (wt), G-CSF deficient mice and G-CSF substituted G-CSF deficient mice followed by assessment of infarct volumes, neurological outcome and sensorimotor function. In addition, immunohistochemistry and real-time PCR of the peri-ischemic area were performed. G-CSF deficient mice showed increased infarct volumes, whereas G-CSF substituted mice had a remarkable reduction in lesion size compared to wt mice. These findings are accompanied by an improvement in neurological and sensorimotor function. G-CSF deficiency resulted in an upregulation of MMP-9 in the direct peri-ischemic tissue. Treatment with G-CSF suppressed the upregulation of MMP-9. Taken together, G-CSF deficiency clearly resulted in enlarged infarct volumes, and worsened neurological outcome. G-CSF substitution abolished these negative effects, led to significant reduced lesion volumes, and improved neurological outcome. G-CSF mediated suppression of MMP-9 further demonstrates that endogenous G-CSF plays a significant role in brain protective mechanisms. We have shown for the first time that endogenous G-CSF is required for brain recovery mechanisms after stroke.     

Accumulation of Potassium and Calcium in Rat Myocardium Exposed to α-1-Adrenoceptor Stimulation

Abstract: Net fluxes of potassium, calcium, sodium and chloride were examined in isolated perfused rat hearts during α-1-adrenoceptor stimulation. The ion measurements were performed in the non-recirculating perfusate. Hearts were exposed to α-1-adrenoceptor stimulation (phenylephrine 5×10^–5 mol/1 in the presence of the β-blocker timolol 10^–6 mol/1). During α-1-adrenoceptor stimulation perfusate potassium fell relatively rapidly by about 0.10 mmol/1 after approximately 100 sec. followed by a slower rise. About 180 sec. after onset of α-1-adrenoceptor stimulation, the potassium level was about 0.06 mmol/1 below the control concentration level. This reduction was eliminated by the α-1-adrenoceptor blocker prazosin (10^–7 mol/1). The effects on net calcium fluxes were measured at two different calcium concentrations. For both concentrations we found a small but statistically significant reduction of the calcium concentration in the perfusate after α-1-adrenoceptor stimulation. Neither sodium nor chloride perfusate concentrations showed statistical significant changes compared to control values. The present observations revealed the existence of α-1-adrenoceptor regulated mechanisms related to a net uptake of both potassium and calcium in rat heart.     

Beneficial effect of modified peptide inhibitor of alpha4 integrins on experimental allergic encephalomyelitis in Lewis rats.

An important event in the pathogenesis of the autoimmune disease multiple sclerosis (MS) is the recruitment of lymphocytes and inflammatory macrophages to the central nervous system (CNS). Recruitment requires adhesive interactions between the leukocytes and the microvascular endothelium, perivascular cells, and astrocytes in the CNS parenchyma. Previous studies using an animal model of MS, experimental allergic encephalomyelitis (EAE), have shown the involvement of the alpha4 integrin VLA-4 (beta4beta1). In the present study, the effect of a modified peptide inhibitor of alpha4 integrins on the clinical course and leukocyte infiltration during EAE is investigated. EAE was either induced actively, by immunizing Lewis rats with whole guinea pig MBP, or passively, by transfer of an MBP-specific T cell line. Treatment with the inhibitor (CS1 ligand mimic) completely prevented both clinical signs and cellular infiltration in passively induced EAE. Peptide treatment of actively induced EAE, which has a more severe disease course than the transfer model, significantly reduced clinical signs although the recruitment of inflammatory cells and induction of MHC class II expression was not prevented. The alpha4 inhibitor did inhibit the adhesion of lymphocytes to primary astrocytes in vitro suggesting a role for astrocyte-leukocyte interactions in the pathogenesis of induced EAE. Astrocytes were found to express an extracellular matrix protein distinct from fibronectin, which shows immune cross-reactivity with the CS1 domain of fibronectin. Our results show that small-molecule inhibitors of alpha4 integrins act therapeutically in EAE possibly by interfering with cell adhesion events involved in this autoimmune disease.     

Training and certifying behavior analysts.

Proper professional certification and training of behavior analysts who work with individuals with autism is critical in ensuring that those individuals receive the highest quality behavior analytic services. This article discusses the current issues surrounding certification of behavior analysts and describes the important features of the Behavior Analyst Certification Board and its credentials. The article also reviews approaches to the training of professional behavior analyst practitioners and discusses appropriate training content for behavior analysts who work with persons with autism. The interrelationship between training and certification is explored.