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Objective: The Global Campaign Against Epilepsy demonstration project in rural China aimed: to reduce the treatment gap and morbidity of people with epilepsy by using community-level interventions; to train and educate health professionals; to dispel stigma; to identify potential for prevention and to develop models of integration of epilepsy control into the local health systems. We report the overall results of the demonstration project, focusing on the prevalence and the change in the treatment gap of epilepsy after an intervention.Methods: Door-to-door epidemiological surveys were carried out before, and 6 months after the end of, an intervention project for epilepsy in rural settings in five provinces of China. The intervention consisted of a treatment programme available to patients without prior appropriate treatment and a public health educational programme about epilepsy. The sampled population in the second survey was 51 644 people.Findings: In the second survey, epilepsy was confirmed in 320 people, yielding a lifetime prevalence of 6.2/1000 and a prevalence of active epilepsy of 4.5/1000. The lifetime prevalence and prevalence of active epilepsy in the first survey were 7.0/1000 and 4.6/1000, respectively. The treatment gap of active epilepsy in the second survey was 49.8%, 12.8 percentage points lower than that of the first survey (62.6%).Conclusion: The results of this study suggest that the intervention measures used were possibly effective and evidently feasible in rural China, contributing to a decrease in the treatment gap of epilepsy. Copyright © 2008 World Health Organization [ABSTRACT FROM AUTHOR]

To evaluate the effectiveness of a combined intervention on knowledge, attitude, and practice (KAP) of people with epilepsy and their families in rural areas of China, random samples of people with epilepsy and their family members from the intervention populations completed questionnaires prior to the intervention (2002, N=975) and 2 years later (N=950). There was no significant difference in important demographic variables between the two samples. KAP levels of patients and their family members improved over the study period. Worry about seizures, discrimination, and medical costs are the principal factors in patients' psychological burden. Psychological burden and inability to concentrate at work are the main influences of the disease on family members. Reduction of the psychological burden of patients and their family members is a significant aspect of treatment to which more attention should be paid in similar future interventions.

Purpose: Information about existing resources available within the countries to tackle the huge medical, social, and economic burden caused by epilepsy is lacking. To fill this information gap, a survey of country resources available for epilepsy care was conducted within the framework of the ILAE/IBE/WHO Global Campaign Against Epilepsy., Methods: The study represents a major collaborative effort involving the World Health Organization (WHO), the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)., Results: Data were collected from 160 countries representing 97.5% of the world population. The information included availability, role, and involvement of professional and patient associations for epilepsy, epilepsy treatment and services including antiepileptic drugs, human resources involved in epilepsy care, teaching in epileptology, disability benefits, and problems encountered by people with epilepsy and health professionals involved in epilepsy care. The data confirm that epilepsy care is grossly inadequate compared with the needs in most countries. In addition, large inequities exist across regions and income groups of countries, with low-income countries having extremely meager resources. Complete results of this survey can be found in the Atlas: Epilepsy Care in the World., Conclusions: The data reinforce the need for urgent, substantial, and systematic action to enhance resources for epilepsy care, especially in low-income countries.

The effects of alpha-tocopherol and its homologues with different chain lengths (6-hydroxy-chromanes: C1, C6, C11) on lipid peroxidation in natural membranes (liver microsomes and mitochondria, brain synaptosomes) and liposomes were studied. It was shown that the antioxidant activity of alpha-tocopherol homologues decreased in the order: C1 greater than C6 greater than C11 greater than alpha-tocopherol (C16). Using fluorescent measurements, the possible reasons underlying these differences were investigated: (i) the distribution between the aqueous media and nonpolar phase of the membrane, which predetermines the binding of alpha-tocopherol homologues to membranes; (ii) the incorporation of alpha-tocopherol homologues into lipid bilayer; (iii) non-uniform distribution (formation of the clusters) of tocopherol homologues in the lipid bilayer; and (iv) transbilayer mobility of alpha-tocopherol homologues and accessibility of the inhibitors for radical-generating centres under enzymically and non-enzymically induced lipid peroxidation. It was demonstrated that: (i) binding of C1 with membranes was less efficient than that of longer-chain homologues (C6, C11, C16); (ii) the level of incorporation of alpha-tocopherol homologues into membranes decreased in a succession alpha-tocopherol C11 greater than C6 greater than C1; (iii) all alpha-tocopherol homologues existed in the lipid bilayer not only in a monomeric form but also associated in clusters thus decreasing the efficiency of radical scavenging; (iv) the short-chain alpha-tocopherol homologue, C1, exhibited a high transbilayer mobility whereas the long-chain one, C16, underwent no transbilayer migration within tens of minutes. The inhibiting effect of alpha-tocopherol esters and C1-acetate was predetermined by their hydrolysis in biomembranes; a strong correlation exists between the rate of the ester hydrolysis and their antioxidant activity in the membrane. In liposomes, in which the esterase activity was absent, alpha-tocopherol esters and C1-acetate exhibited very low lipid peroxidation inhibition.

The peroxidative radicals arizing after destruction of exogenous hydroperoxides catalyzed by cytochrome P-450, carried out important functions in induction of lipid peroxidation, dependent on organic hydroperoxides. Only a slight inhibitory effect of singlet oxygen and anion radicals of superoxide on organic hydroperoxide dependent process of lipid peroxidation suggested that these active forms of oxygen participated apparently in lipid peroxidation. The traps of hydroxyl radicals (.OH) did not affect the lipid peroxidation induced by organic hydroperoxides. A mechanism is discussed for generation and function of peroxidative radicals as well as of active oxygen forms in lipid peroxidation, induced by organic hydroperoxides in liver microsomal membranes.

In the presence of Fe2+ and ascorbate lipid peroxidation in mitochondrial membranes is induced by incubation of membrane fragments devoid of catalase activity with amines which are the substrates of monoamine oxidases of the type B (2-phenylethylamine, benzylamine) or transformed monoamine oxidases of the type A (cadaverine). The highest stimulation of lipid peroxidation is observed in the samples containing both cadaverine and benzylamine. On the contrary, the substrate of the monoamine oxidases of the type A, serotonin, causes an antioxidative effect under these conditions. The necessary prerequisites for lipid peroxidation induction in mitochondria during their incubation with amines are i) the absence of catalase activity in the biomembranes and, ii) the presence of physiological concentrations of Fe2+. Physiological concentrations of ascorbate or pH shifts cause additional stimulation of lipid peroxidation.

Hyperoxia brought about substantial accumulation of primary and end products of lipid peroxidation (LPO) and a significant lowering of alpha-tocopherol content in rat brain tissues. Preinjection of animals with synthetic and natural antioxidants (4-methyl-2,6-ditretbutylphenol and alpha-tocopherol) prevented LPO activation and decreased the frequency of epileptiform seizures induced by hyperoxia. Administration of a mixture of unsaturated fatty acids led to an opposite effect. The changes in the properties of serotonin receptors were found to be dependent on the hyperoxia-induced LPO. These changes were marked by the reduced specific binding of serotonin with neuronal membranes of the rat brain cortex. The data obtained allowed the conclusion about the key role played by LPO activation in toxic action of hyperbaric activation on the brain.

The effect of synthetic (BHT, 2,2,5,7,8-pentamethyl-6-hydroxychroman) and natural (alpha-tocopherol) antioxidants on Ca++-transporting systems was compared in platelets, brain synaptosomes, and skeletal muscle sarcoplasmic reticulum. It was shown that synthetic antioxidants, in contrast to alpha-tocopherol, induced Ca++-release manifested in platelet aggregation, stimulation of 5-hydroxytryptamine release by synaptosomes, synaptosome depolarization and inhibition of Ca++-transport and Ca++-ATPase activity in the sarcoplasmic reticulum. The disturbances of Ca++-homeostasis induced by synthetic antioxidants are considered as molecular mechanisms of complications encountered upon their application.

NAD (P) H-dependent enzymic systems, both of lipid peroxidation and chlorpromazine oxidative metabolism are shown to be localized in the microsomal fractions from human and rat brain. Hydroxy-derivatives of chlorpromazine (e.g. 7-OH-chlorpromazine) formed in the course of enzymic NADPH-dependent metabolism possess antioxidant activity and inhibit lipid peroxidation in the brain microsomes. The properties of enzymic NAD (P) H-dependent oxigenase systems in the membranes of the microsomal reticulum of the liver and brain are compared.

UV spectrophotometry and high-resolution NMR spectrometry have demonstrated the formation of the complexes of ionol and fatty acids. This formation occurs as a result of the two types of interactions: 1/hydrogen bond formation between ionol OH-group and the carboxylic group of a fatty acid; 2/van der Waals interactions between the hydrogen chain of a fatty acid and tret -butyl groups of ionol. The latter interaction becomes more powerful with increase in fatty acid unsaturation. The molecular structure of the complexes of ionol with fatty acids is suggested.

It was shown that oxidation of adrenaline to adrenochrome in microsomal membranes of the brain and liver in the presence of NADP . H2 or NAD . H2 is mainly accounted for by the formation of a superoxide anion radical. The formation of adrenochrome from adrenalin was found to depend on organic hydroperoxides (natural and synthetic). The organic hydroperoxide-dependent oxidation of adrenochrome involves singlet oxygen. In microsomal fractions of the liver the organic peroxide-dependent oxidation of adrenalin was catalyzed by cytochrome P-450.

A study of resistance to osmotic shock of peripheral blood lymphocytes from healthy donors and schizophrenics demonstrated two lymphocyte subpopulations: a low resistant subpopulation (about 20%) and high resistant subpopulation (about 80%). The lymphocytes from donors belonging to the former subpopulation popossess increased adhesiveness. 60% of schizophrenic patients lack the subpopulation of low resistant lymphocytes. Abnormal resistance to osmotic shock is characteristic of highly adhesive lymphocytes.

The report is concerned with the action of the serum of schizophrenic patients on the physiological state of lymphocytes in normal donors. It was established that during the early stages of incubation the action of the serum in schizophrenic patients evokes the activation of lymphocytes in normal donors, that is seen in changes of the ultrastructure and adhesive properties of these cells. On the late stages of cultivation the serum of patients destroys 13.4 +/- 5.9% of lymphocytes of normal donors. In remaining population 21% of lymphocytes lose their capability to react to PHA stimulation by an increase of DNA content.

Using ESR-spin probes and 1H-NMR-spectroscopy methods the effect of alpha-tocopherol on liposome microviscosity has been studied. alpha-Tocopherol has been shown to remove the chaotropic action of free fatty acids on bilayer. The stabilization effect found has a common nature and does not depend on the chemical structure of the phopsholipid functional polar groups, the unsaturation degree of free fatty acids as well as fatty acids residua entering into phospholipid composition. Analog of alpha-tocopherol without phytol chain 2,2,5,7,8-penthamethyl-6-oxychroman does not show the stabilizing effect on the microviscosity of lipid bilayer under the action of free fatty acids. It indicates that both chromanol nucleus and phytol chain of alpha-tocopherol molecule are necessary for stabilizing action. The data obtained allow to suppose that the interaction of alpha-tocopherol with free fatty acids may be one of the molecular mechanisms of lipid bilayer microvicosity stabilization.

The resistance of peripheral blood lymphocytes was estimated in normal subjects and schizophrenic patients with reference to hypoosmotic effects. It was shown that in normal subjects about 20% of the lymphocytes were slightly resistant. In 60% of the schizophrenic patients the fraction of the slightly resistant lymphocytes was found to be sharply lowered. The content of those cells in the blood of patients with different forms of the disease course was different: patients with the periodic form showed the minimal, and patients with continuously progressing form the maximal deviation from normal. Patients with the schubweise form occupied an intermediate place. Incubation of the lymphocytes of the healthy donors in the serum of schizophrenic patients led to selective destruction of the donor' slightly resistant cells. A statistically significant correlation between the destructive capacity of the patients' serum and the lowering of the content of the slightly resistant lymphocytes in those patients was observed.

Emotional-pain stress leads to accumulation of lipid peroxidation products in rat brain tissues and to an increase in the number of antibrain antibodies against water-soluble and membrane-bound antigens in rat blood. An injection of the free radical scavenger, 4-methyl-2.6-di-tert-butylphenol to experimental animals eliminates the accumulation of lipid peroxidation products "in vivo" and completely prevents the appearance of antibrain antibodies. The activation of lipid peroxidation under stress may be regarded as a possible cause of the brain-specific antibodies release into the blood flow.

Using the fluorescent probe technique, it was shown that activation of lipid peroxidation decreases the value of transmembrane potential of rat brain synaptosomes. Depolarization of synaptosomes may be due to the impairment of the "barrier" properties of synaptosomal membranes and the decrease in Na,K-ATPase activity. alpha-Tocopherol and its model derivative devoid of the phytol chain--2,2,5,7,8-pentamethyl-6-oxychromanol--stabilize the transmembrane potential value during inhibition of lipid peroxidation. alpha-Tocopherol acetate causes no stabilizing or inhibiting effects. Unlike 2,2,5,7,8-pentamethyl-6-oxychromanol, alpha-tocopherol exerts a structuralizing action which manifests itself in the stabilization of the synaptosomal membrane potential during incomplete inhibition of lipid peroxidation. The previously established ability of alpha-tocopherol to protect synaptosomes from the damaging action of phospholipases and the experimental results of this work permit to regard vitamin E as a universal stabilizer of brain synaptosomal membranes.

Using fluorescent and ESR-spin probes, the effects of phospholipases A2, C and D on rat brain synaptosomal membranes were investigated. It was shown that the exposure of synaptosomal membranes to phospholipases A2, C and D results in their depolarization and an increase of the negative surface potential. In the case of phospholipases A2 and C, these changes are associated with a decrease of the microviscosity of the membrane lipid bilayer. alpha-Tocopherol stabilizes synaptosomal membranes against the damaging action of the phospholipases. This stabilization consists in the reconstitution of the transmembrane potential and an increase of microviscosity of the phospholipase-treated membranes. The stabilizing effect of alpha-tocopherol is due to the binding of phospholipid hydrolysis products, but not to the inhibition of phospholipases. The observed stabilization of synaptosomal membranes by alpha-tocopherol is regarded as a possible mechanism of biological action of vitamin E on biomembranes.

The localization of amino phospholipids (phosphatidyl ethanolamine, phosphatidyl serine) and their fatty acid composition in the outer and inner monolayers of plasma membranes from rat brain synaptosomes and retinal photoreceptors in the fish Theragra chalcograma have been studied by chemical modification. The mobility of the lipid components of these membranes was investigated by fluorescent and EPR spin probing techniques after transformation of outer (chemical and physical) signals. The data obtained are discussed in terms of molecular organization of the lipids and of the changes in the mobility of the lipid components of plasma membranes from brain synaptosomes and retinal photoreceptors during transmembrane transmission of the signal.

The main achievements in the field of genetics, biochemistry, and immunology of schizophrenia in the laboratories of European research centers are surveyed. Despite the rapid development of scientific research techniques and methodology, the abundant hypotheses on the pathogenesis of schizophrenia are riddled with so many contradictory facts that it is impossible to formulate any concrete model of the disease. One factor impeding the progress of biological research in schizophrenia is the inadequate development of standardized clinical descriptions. This is an obstacle to the study of clinical-biological correlates, which are among the principal criteria used to verify the importance of biological parameters chosen for study in the pathogenesis of the disease. A current strategy in the biology of schizophrenia, which may obviate some of those problems, is the discovery and study of biological markers.

UV spectroscopy, polarography and fluorescence of Schiff's bases were used to study the time course of emotional pain stress-induced accumulation of the primary and secondary products of lipoperoxidation (LPO) in different tissues of Wistar rats and to appraise the effect of gamma-hydroxybutyric acid (GHBA) and 4-methyl-2,6-ditretbutylphenol (ionol) on LPO induction. LPO activation was shown to be retained after emotional pain stress for a long enough period of time. This activation may last from 2 to 5 days depending on the organ. Pretreatment with GHBA or ionol completely reverses LPO activation.

The authors studied the cytotoxic activity of the lymphocytes in the peripheral blood of 16 schizophrenic patients and 14 normal donors in respect to autological erythrocytes. It was demonstrated that the hemolytic activity of the lymphocytes of patients was significantly higher, than in the control group. Activated cells possess cytotoxic properties.

The effects of free radical scavengers of different chemical structure (hydroxypyridines, hindered phenols, hydroxyphenothiazines) on processes of 3H-hydroxytryptamine uptake and release by rat brain synaptosomes were studied. All free radical scavengers used inhibited 3T-hydroxytryptamine uptake and stimulated 3H-hydroxytryptamine release, with the efficacy being reduced in the following order: 7-hydroxyaminazine greater than butylated hydroxytoluene greater than paginol-2-methyl-6-ethyl-3-hydroxypyridine greater than alpha-tocopherol. The effects of free radical scavengers were eliminated in the presence of EGTA or after cooling to 4 degrees C.

The role of phospholipid hydrolysis by phospholipase A2 and lipid peroxidation in changes of the properties of beta-adrenoreceptors in rat brain synaptosomes in severe emotional painful stress (EPS) has been evaluated. It has been shown that EPS does not influence lipid and fatty acid content of synaptosomal membranes but significantly increases the amount of lipid peroxidation products. Activation of lipid peroxidation in EPS causes a decrease in specific binding of 3H-dihydroalprenolol. The free radical scavenger, 4-methyl-2,6-di(tret-butyl)phenol completely prevents activation of lipid peroxidation and eliminates the disturbances in ligand-receptor interactions in EPS.

Hyperbaric oxygenation (1 atm. of pure oxygen, 60 min. exposure) resulted in a sharp increase of the endogenous lipoperoxidation level in humans which was evaluated by the pentane content in the exhaled air. That activation of endogenous lipid peroxidation was a short-term process: 2-3-fold increase of pentane content 10 min after exposure to hyperbaric oxygenation and levelling off to control values in 1 hour. It is recommended to use determination of endogenous lipid peroxidation by the pentane content in the exhaled air in order to find optimal regimens of hyperbaric oxygenation.

The development of bemegride-induced generalized epileptic activity in rats was shown to reduce the constant (CB). of specific 3H-diazepam binding with synaptic membranes from 0.23 nM-1 to 0.15 nM-1 and to increase the maximum number of membrane binding sites (Bmax) from 410 fmol/mg protein to 550 fmol/mg protein. It is assumed that the changes of benzodiazepine receptor properties are due to alteration in physico-chemical characteristics of synaptic membrane lipids resulting from the activation of lipid peroxidation.

It was demonstrated that the processes of lipid peroxidation in brain tissues of rats induced by hyperoxia and Fe-ascorbate system in vivo and in vitro significantly influence specific binding of serotonin and diazepam. Lipid peroxidation caused various changes in the ability to bind utilized ligands: 3H-serotonin binding decreased by 53%, while that of 3H-diazepam increased by 30%. Preliminary administration of the synthetic antioxidant 4-methyl-2,6-ditretbutylphenol prevented these changes.

Stereoconfiguration of alpha-tocopherol-linoleic acid complex was studied using high resolution IH-NMR-spectroscopy. The addition of a fatty acid (linoleate) to alpha-tocopherol solution in CDCl3 resulted in the broadening of IH-NMR lines for OH- and phe-CH3-alpha-tocopherol groups. No changes in chemical shift values of IH-NMR lines for linoleic acid were observed after the addition of alpha-tocopherol to linoleic acid solution in CDCl3. It is concluded that in the complexes formed linoleic acid is located in the phenolic ring plane of alpha-tocopherol. The conclusion is supported by the data obtained on molecular models.

The blood serum of schizophrenic patients and three of its studied fractions (gamma-globulins and remaining after elimination of gamma-globulins and ultrafiltrate protein fractions) inhibit the lymphocyte response of normals to PHA stimulation (an increase of the DNA content in cells). An insignificant inhibitor effect in the blood serum of normals was seen only in the protein fraction. The PHA precipitating activity of the blood serum in schizophrenic patients which is mainly connected with its protein fraction is increased by 30%. However, there are no correlations between this blood serum activity and its capability to inhibit the response of lymphocytes to PHA stimulation.