Scalp EEG for the diagnosis of epilepsy and photosensitivity in the baboon

Spontaneous seizures have been observed in several baboon species housed at the Southwest National Primate Research Center (SNPRC), including Papio hamadryas anubis and cynocephalus/anubis, hamadryas/anubis, and papio/anubis hybrids. The goal of this study was to establish a noninvasive, reliable electroencephalographic technique to characterize epilepsy phenotypes and assess photosensitivity in these subspecies. Thirty baboons with witnessed seizures, and 15 asymptomatic baboons underwent scalp electroencephalograms (EEGs) with photic stimulation (PS). The sensitivity and specificity of surface EEG for identifying interictal epileptic discharges (IEDs) in baboons with witnessed seizures were examined. The morphology of IEDs, electroclinical features of seizures and responses to PS, reproducibility of EEG findings, and intrarater reliability were also evaluated. Twenty-three seizure baboons (77%) demonstrated IEDs, predominantly with frequencies of 4-6 Hz in 18 baboons and 2-3 Hz in six baboons. Two seizure animals had a mixture of 2-3-Hz and 4-6-Hz IEDs. All animals with 2-3-Hz IEDs were 3 years old or younger. Myoclonic seizures (MS) and generalized tonic-clonic seizures (GTCS) were recorded in 13 baboons (43%). PS activated IEDs in 15 baboons (50%) and seizures in nine baboons. The presence of IEDs or seizures was not associated with a particular gender or species (Fisher exact test, alpha=0.05). Seizures were more common in animals >3 years old, while PS-induced IEDs and seizures were more prevalent in P.h. anubis/cynocephalus crosses compared to P.h. anubis. In the asymptomatic controls, IEDs were recorded in five baboons (33%), and photoparoxysmal responses were observed in two (13%). Surface EEG is a sensitive and reliable instrument for characterizing the epilepsy encountered in Papio species. Electroclinically, the seizure animals had generalized epilepsy with photosensitivity. The variation in IED morphology may be age-related or it may reflect different epileptic phenotypes. Ketamine provoked IEDs and seizures in most seizure animals and only in a few asymptomatic baboons; therefore, it may enhance the sensitivity of surface EEG for detecting a predisposition to epilepsy.     

Dosimetry of total skin electron irradiation

Elaboration of such a simple technique for total skin electron irradiation which ensures good dose homogeneity and minimal x-ray background dose. MATERIALS AND METHODS: We started large electron field irradiations with the Neptun 10p linear accelerator in the National Institute of Oncology -Budapest in 1986. After the installation of the Siemens Mevatron KD linear accelerator it was possible to introduce the modified Stanford technique. This technique satisfies better the requirements given in the objective. The required field size of 200x75 cm is produced as a result of two fields with 30 degrees angular separation (dual field) at a source skin distance of 465 cm. The patient's body is exposed to six dual electron fields. The electron energy is 6 MeV. Despite the long source skin distance the treatment time is relatively short due to the high dose rate (940 mu/min) capability of our Mevatron KD. The in air dose profiles were measured in miniphantom with semiconductor detector. Depth dose curves were measured in water and in polystyrene phantom with semiconductor detector and with films. RESULTS: The measured dose homogeneity of the 6 MeV energy dual field with 30 degrees angular separation is within +/- 5%in a 200x75cm plane field. The depth of dose maximum of the resulting dose distribution of six dual field irradiation is between 2 mm and 5 mm, while the depth of 80% isodose curve is about 8 mm. The total body x-ray background dose is less than 1% of the skin dose. CONCLUSION: The modified Stanford technique adapted to our Mevatron KD linear accelerator is suitable for total skin electron beam therapy.     

Regulatory relationship among piwi, pumilio, and bag-of-marbles in Drosophila germline stem cell self-renewal and differentiation

The transition from a Drosophila ovarian germline stem cell (GSC) to its differentiated daughter cell, the cystoblast, is controlled by both niche signals and intrinsic factors. piwi and pumilio (pum) are essential for GSC self-renewal, whereas bag-of-marbles (bam) is required for cystoblast differentiation. We demonstrate that Piwi and Bam proteins are expressed independently of each other in reciprocal patterns in GSCs and cystoblasts. However, overexpression of either one antagonizes the other in these cells. Furthermore, piwi;bam double mutants phenocopy the bam mutant. This epistasis reflects the niche signaling function of piwi because depleting piwi from niche cells in bam mutant ovaries also phenocopies bam mutants. Thus, bam is epistatic to niche Piwi, but not germline Piwi function. Despite this, bam- ovaries lacking germline Piwi contain approximately 4-fold fewer germ cells than bam- ovaries, consistent with the role of germline Piwi in promoting GSC mitosis by 4-fold. Finally, pum is epistatic to bam, indicating that niche Piwi does not regulate Bam-C through Pum. We propose that niche Piwi maintains GSCs by repressing bam expression in GSCs, which consequently prevents Bam from downregulating Pum/Nos function in repressing the translation of differentiation genes and germline Piwi function in promoting germ cell division.     

Radiotherapy of lung cancer: survey and latest evidences

Based on their experience, the authors survey Hungarian and international literature for changes of indications, techniques and results in lung cancer radiotherapy. At the end of historical review, the latest evidence-based levels of different indications, the up-to-date techniques and the expected results are discussed.     

Therapy of brain metastasis based on the RPA classification

RPA classification of patients suffering from brain metastases is not widely used in Hungary. The authors reviewed the RPA disposition-based therapeutic recommendations in the literature. Retrospective analysis of their 123 brain metastatic cases showed 3.8 months median, 34.1% 1-year and 7.9% 2-year overall survival. Patient number and median survival in subgroups: RPA 1: 42/14 months, RPA 2: 38/6,2 months, RPA 3a: 6/3.1 months, 3b: 13/2 months, 3c: 10/0.7 months. Median survival of patients with brain metastases from cancer of unknown primary (CUP) was 3 months. In RPA class 1 and 2, 10% undertreatment has been found for solid brain metastases, and all of the 3c patients were over-treated according to literature recommendations. The authors strongly recommend the use of RPA classification in the management of brain metastases and in contemplation of the capacity of radiotherapy/neurosurgery and oncology.     

Elevated Levels of Asymmetric Dimethylarginine (ADMA) in the Pericardial Fluid of Cardiac Patients Correlate with Cardiac Hypertrophy

Background

Pericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology.

Methods

L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined.

Results

We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7±4.6 μmol/L vs. 58.1±4.9 μmol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9±0.0 μmol/L vs. 0.7±0.0 μmol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VR_plasma: 76.1±6.6 vs. CABG_plasma: 125.4±10.7, p = 0.004; VR_PF: 81.7±4.8 vs. CABG_PF: 110.4±7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7±0.5 mm vs. 11.9±0.4 mm, p = 0.000); posterior wall thickness (12.6±0.3 mm vs. 11.5±0.2 mm, p = 0.000); left ventricular (LV) mass (318.6±23.5 g vs. 234.6±12.3 g, p = 0.007); right ventricular (RV) (33.9±0.9 cm² vs. 29.7±0.7 cm², p = 0.004); right atrial (18.6±1.0 cm² vs. 15.4±0.6 cm², p = 0.020); left atrial (19.8±1.0 cm² vs. 16.9±0.6 cm², p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR.

Conclusion

We suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling.     

Aging exacerbates hypertension‐induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection

Recent studies demonstrate that aging exacerbates hypertension‐induced cognitive decline, but the specific age‐related mechanisms remain elusive. Cerebral microhemorrhages (CMHs) are associated with rupture of small intracerebral vessels and are thought to progressively impair neuronal function. To determine whether aging exacerbates hypertension‐induced CMHs young (3 months) and aged (24 months) mice were treated with angiotensin II plus L‐NAME. We found that the same level of hypertension leads to significantly earlier onset and increased incidence of CMHs in aged mice than in young mice, as shown by neurological examination, gait analysis, and histological assessment of CMHs in serial brain sections. Hypertension‐induced cerebrovascular oxidative stress and redox‐sensitive activation of matrix metalloproteinases (MMPs) were increased in aging. Treatment of aged mice with resveratrol significantly attenuated hypertension‐induced oxidative stress, inhibited vascular MMP activation, significantly delayed the onset, and reduced the incidence of CMHs. Collectively, aging promotes CMHs in mice likely by exacerbating hypertension‐induced oxidative stress and MMP activation. Therapeutic strategies that reduce microvascular oxidative stress and MMP activation may be useful for the prevention of CMHs, protecting neurocognitive function in high‐risk elderly patients.     

Quantification of plant surface metabolites by matrix‐assisted laser desorption–ionization mass spectrometry imaging: glucosinolates on Arabidopsis thaliana leaves

The localization of metabolites on plant surfaces has been problematic because of the limitations of current methodologies. Attempts to localize glucosinolates, the sulfur‐rich defense compounds of the order Brassicales, on leaf surfaces have given many contradictory results depending on the method employed. Here we developed a matrix‐assisted laser desorption–ionization (MALDI) mass spectrometry protocol to detect surface glucosinolates on Arabidopsis thaliana leaves by applying the MALDI matrix through sublimation. Quantification was accomplished by spotting glucosinolate standards directly on the leaf surface. The A. thaliana leaf surface was found to contain approximately 15 nmol of total glucosinolate per leaf with about 50 pmol mm^?2 on abaxial (bottom) surfaces and 15–30 times less on adaxial (top) surfaces. Of the major compounds detected, 4‐methylsulfinylbutylglucosinolate, indol‐3‐ylmethylglucosinolate, and 8‐methylsulfinyloctylglucosinolate were also major components of the leaf interior, but the second most abundant glucosinolate on the surface, 4‐methylthiobutylglucosinolate, was only a trace component of the interior. Distribution on the surface was relatively uniform in contrast to the interior, where glucosinolates were distributed more abundantly in the midrib and periphery than the rest of the leaf. These results were confirmed by two other mass spectrometry‐based techniques, laser ablation electrospray ionization and liquid extraction surface analysis. The concentrations of glucosinolates on A. thaliana leaf surfaces were found to be sufficient to attract the specialist feeding lepidopterans Plutella xylostella and Pieris rapae for oviposition. The methods employed here should be easily applied to other plant species and metabolites.