Distribution of Spatial Complexity of EEG in Idiopathic Generalized Epilepsy and Its Change After Chronic Valproate Therapy

The objective of this study was to investigate the global and regional spatial synchrony of the EEG background activity, and to assess the effect of chronic valproate therapy on spatial synchrony. 15 idiopathic generalized epilepsy (IGE) patients were examined and compared to 16 normal controls. Resting EEG with 19 channels was investigated before and during chronic administration of valproate (VPA). Omega, a single-valued measure of spatial covariance complexity, was calculated to assess the degree of spatial synchrony of EEG. Furthermore, a new parameter was defined to characterize the distribution of spatial synchrony (Antero-Posterior Complexity Ratio, APCR). Global Omega complexity was significantly lower in IGE compared to controls, while regional complexity showed significant differences only in the anterior region: the IGE group showed lower complexity. APCR was significantly lower in IGE. VPA therapy (1) lowered the global complexity, (2) increased regional complexity in the anterior region, but decreased it in the posterior region, and (3) increased APCR. In IGE lower complexity, i.e. enhanced spatial synchrony, was found, especially in the anterior cortical area. VPA modified the distribution of spatial synchrony in IGE patients towards that of normal controls, although the effect is not identical with full normalization of cortical bioelectric activity. Whether the observed change of spatial synchrony distribution may reflect the normalizing effect of valproate on the brain state is worth further investigation.     

Peripheral nerve injury influences the disinhibition induced by focal ischaemia in the rat motor cortex

Photothrombotic lesions were produced in the rat primary motor cortex, and the brain excitability was assessed in a paired-pulse stimulation protocol by transcranial recording, in parallel at 16 points of the frontal cortex, including the insulted and the surrounding areas. The cortical lesion reduced the inhibition in the extended frontal cortex, with a delay of a few minutes. Unilateral facial nerve transection, however, accelerated the widespread disinhibition. Although the mechanism is not clear in detail, both peripheral and central injury-induced disinhibition may have a significant impact on the recovery of the function.     

Characterization of functional Fc receptor material from human lymphoblastoid cell lines—I. Large scale purification and biochemical analysis

A receptor, specific for the Fc portion of IgG, was purified from several lymphoblastoid cell lines using immunoadsorbents prepared from either immobilized antigen-antibody or heat aggregated immunoglobulin columns. Biochemical analysis revealed that the receptor is a multimeric glycoprotein with a subunit polypeptide mass of 46,000 daltons, held together by disulfide bonds. Integrity of these disulfide bonds is essential for successful binding of the receptor complexes to the Fc portion of complexed Ig. The association of receptor with immunoglobulin, once formed, was found to be highly stable even in the presence of low pH or high concentrations of chaotropic agents. The receptor, present on the surface of several human lymphoblastoid cell lines, was found to represent as much as 4–5% of the total cytoplasmic membrane proteins. The receptor showed no affinity to staphylococcal Protein A, but did bind to Protein A-immunoglobulin complexes, indicating separate binding sites for these proteins on the Fc portion of IgG. The purified receptor was found to be insoluble in aqueous buffers after detergent removal. Nevertheless, in functional assays, the precipitated receptor was able to agglutinate sheep erythrocytes sensitized with rabbit anti-SRBC IgG, but not unsensitized SRBC or SRBC sensitized with IgM. Antiserum against the receptor was found to react with a specific subclass of normal human or mouse peripheral blood lymphocyte, and with all Fc receptor positive but not with Fc receptor negative cell lines tested.     

Are the urban poor vulnerable to non-communicable diseases? A survey of risk factors for non-communicable diseases in urban slums of Faridabad

BACKGROUND: Non-communicable diseases have modifiable risk factors, which are easy to measure and can help in planning effective interventions. We established a community-based sentinel surveillance to estimate the prevalence and level of common risk factors for major non-communicable diseases as part of a joint Indian Council of Medical Research/WHO initiative. METHODS: This survey was done from February 2003 to June 2004 and included 1260 men and 1 304 women 15-64 years of age living in urban slum areas of Ballabgarh block, Faridabad district, Haryana. A list of all slums in Ballabgarh block was obtained from the Municipal Corporation of Faridabad. Slums were selected by stratified cluster sampling. All households in the selected slums were visited and men and women interviewed in alternate households. The study instrument was based on the STEPS approach of WHO. It included questions related to tobacco use, alcohol intake, diet, physical activity, and history of treatment for hypertension and diabetes mellitus. Height, weight, waist circumference and blood pressure were measured. To estimate prevalence at the population level, age adjustment was done using the urban Faridabad population structure from the 2001 Census of India. RESULTS: The age-adjusted prevalence of smoking among men was 36.5% compared with 7% in women. Bidi was the predominant form of smoked tobacco used. The use of smokeless tobacco was reported by 10.2% of men and 2.9% of women. While 26% of men reported consuming alcohol in the past 1 year, none of the women did. The mean number of servings per day of fruits and vegetables was 2.7 for men compared with 2.2 for women. Overall, only 7.9% and 5.4% of men and women, respectively took > or = 5 servings per day of fruits and vegetables. Women were more likely to be physically inactive compared with men (14.8% v. 55%); 67% of men and 22.8% of women reported mean physical activity > 150 minutes per week. The mean body mass index (BMI) was lower in men than in women (20.9 v. 21.9 kg/m2). The prevalence of overweight (BMI > or = 25 kg/m2)) was 16% among men and 21.9% among women. The prevalence of hypertension (blood pressure > or = 1 40/> or = 90 mmHg or on an antihypertensive drug) was 17.2% in men and 15.8% in women. CONCLUSION: The high prevalence of risk factors for noncommunicable diseases across all age groups in this urban slum community indicates the likelihood of a high future burden of illness. Immediate action for prevention and control is required to prevent the situation from worsening.     

Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis

We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [(14)C]AA as a tracer substrate and chromatographic determination. The recurrent epileptic seizures of male Wistar rats were induced every second day with 3-aminopyridine (3-AP, 25 mg/kg ip) for two weeks. In the chronic 3-AP model, the earlier epileptic insults resulted in a decreased incidence of limbic seizures and higher survival rate at later administration of 3-AP. After 3-AP treatment, the formation of lipoxygenase products was unchanged, but the total amount of cyclooxygenase (COX) metabolites was decreased both in platelets and brain microvessels. The reduction in COX-mediated eicosanoid synthesis after recurrent seizures was due to the decreased synthesis of vasodilator and vasoconstrictor COX metabolites. In platelets, the 3-AP-treatment reduced the synthesis of vasodilator prostacyclin (PGI(2)), prostaglandin E(2) (PGE(2)) and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D(2) (PGD(2)) remained unchanged. In isolated brain capillaries, the PGD(2), PGE(2) and 12-HHT synthesis was decreased after recurrent seizures. As for the vasoconstrictor COX metabolites, both platelets and brain microvessels synthesized significantly lesser amount of prostaglandin F(2alpha) (PGF(2alpha)) and thromboxane A(2) (TxA(2)) upon 3-AP administration. Our results indicate that platelets and isolated brain capillaries synthesize significantly lesser amount of COX metabolites after chronic 3-AP treatment. The decreased conversion of AA into different COX products may play a role in the neuroprotective/preconditional adaptation of the brain against subsequent seizures.     

Expression in childhood primary brain tumors of NY-ESO-1, a cancer/testis antigen: an immunohistochemical study

BACKGROUND: NY-ESO-1 is a human gene that codes for antigens that are expressed in malignancies of various histological types, but not in normal tissues, except the testes. The expression of NY-ESO-1 in intracranial brain tumors including astrocytomas (ASTRs) and medulloblastomas (MEDs)/primitive neuroectodermal tumors (PNETs) was examined since the expression of NY-ESO-1 has only previously been explored in depth in neuroblastomas. MATERIALS AND METHODS: During our immunohistochemical study, a sensitive, four-step, alkaline phosphatase-conjugated antigen detection technique was employed. The expression of NY-ESO-1 was thereby examined in 6 cases of MED/PNET and 14 cases of ASTR. RESULTS: All 6 MED/PNET cases demonstrated high levels of immunoreactivity (overexpression) with the highest immunostaining intensity grades A and B. In the astrocytic tumors of various subtypes examined, the level of NY-ESO-1 expression was not as strong as that in MEDs/PNETs. However, there was a significant increase in expression level when comparing low-grade pilocytic ASTRs to high-grade anaplastic ASTRs and glioblastomas. CONCLUSION: As evidenced by our results, NY-ESO-1 overexpression increases as the malignancy grade of the astrocytic tumors increases. These data suggest that antigen-directed immunotherapy of primary brain tumors could target cancer/testis antigens (CTAs), especially those expressed at higher frequency such as NY-ESO-1.     

Protection of NOD mice from type 1 diabetes after oral inoculation with vaccinia viruses expressing adjuvanted islet autoantigens

Oral administration of autoantigens and allergens can delay or suppress clinical disease in experimental autoimmune and allergic disorders. However, repeated feeding of large amounts of the tolerogens is required over long periods and is only partially effective in animals systemically sensitized to the ingested antigen. Enhanced suppression of type 1 autoimmune diabetes insulitis and hyperglycemia was demonstrated in both naive and immune animals following oral inoculation with plant-based antigens coupled to the cholera toxin B subunit (CTB). Thus, plant-synthesized antigens linked to the CTB adjuvant, can enhance suppression of inflammatory TH1 lymphocyte-mediated autoreactivity in both naive and immune animals. To stimulate adjuvant-autoantigen fusion protein biosynthesis in the gut mucosae, the authors evaluated oral inoculation of juvenile non-obese diabetic (NOD) mice with recombinant vaccinia virus (rVV) expressing fusion genes encoding CTB linked to the pancreatic islet autoantigens proinsulin (INS) and a 55-kDa C-terminal peptide from glutamate decarboxylase (GAD55). Hyperglycemia in both rVV-CTB:: INS and rVV-CTB:: GAD inoculated mice was substantially reduced in comparison with the uninoculated mouse control. Oral inoculation with rVV carrying the CTB::INS fusion gene generated a significant reduction in insulitis. An increase in IgG1 in comparison with IgG2c antibody isotype titers in rVV-CTB::INS infected mice suggested possible activation of autoantigen specific Th2 lymphocytes. The experimental results demonstrate feasibility of using vaccinia virus oral delivery of adjuvanted autoantigens to the mucosae of prediabetic mice for suppression and therapy of type 1 autoimmune diabetes.     

Ivermectin Interacts With Human ABCG2

Ivermectin is an antiparasitic drug frequently administered to humans. It has a limited brain exposure that is attributed to the efflux activity of ABCB1/Abcb1. ABCG2/Abcg2 is also a major transporter present in most pharmacologically important barriers. However, interaction of ivermectin with Abcg2 shows species specificity and in many studies was confounded by the masking effect of ABCB1/Abcb1. In this study using cellular and membrane assays we show that ivermectin displays a high-affinity interaction with human ABCG2 with IC₅₀ values in the 1–1.5 µM range. This interaction may have implications in human ABCG2-mediated drug–drug interactions of ivermectin.