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Purpose: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappaB (NFkappaB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control., Method: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors., Results: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels., Discussion: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.

Epilepsy is the most common neurological disorder, approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Furthermore, the evidence from the last 10 years suggests that melatonin has an important role in the epileptogenesis process and influences the cardiovascular system as well. The positive effect of melatonin has been demonstrated against different convulsive stimuli in several rodents, including seizures induced by pentylenetetrazole kainate, glutamate, maximal electrical shock and electrically kindled stimulation of amygdala. Clinical studies have also demonstrated a positive role of melatonin on the seizure frequency in children and reduced spiking activity and seizure frequency in patients with intractable epilepsy. In the rat hearts, studies in vivo and in vitro using pharmacological concentrations of melatonin confirmed an anti-arrhythmic effect of this hormone and studies in humans have been shown that chronic heart disease patients have significantly lower melatonin levels in their blood stream than do normal individuals. Thus, caution should be taken in generalization of these findings to epileptic population. Moreover, it is important to note that when dealing with intractable epilepsy that do not respond to any conventional treatment, the additional of melatonin may be evaluated. Taken together, in this paper we suggested a possible relationship between cardiac abnormalities, melatonin and SUDEP.

Several studies have demonstrated the anticonvulsant effect of melatonin. In view of the positive effects of physical exercise in epilepsy, this study analyzed the influence of physical exercise program on the amygdala kindling development in pinealectomized rats. Animals were divided into six groups: pinealectomized rats (PX), sham rats (SHAM), control rats (CTL), pinealectomized rats submitted to an aerobic exercise program (PX ATL), sham rats submitted to an aerobic exercise program (SHAM ATL) and control rats submitted to an aerobic exercise program (CTL ATL). The stimulus parameters consisted of 60 Hz frequency, diphasic square pulses of 1 ms duration applied for 2 s. The mean number of stimulations and the after-discharge (AD) duration for each stage of kindling were similar among CTL and SHAM animals. PX animals showed particular characteristics during kindling development. They did not present stage 1 and spent a shorter time in stage 2 in relation to the CTL and SHAM animals. Consequently, the AD duration and number of stimulations required to reach stage 5 was lower for the PX group when compared to the CTL and SHAM groups. Concerning the exercising groups, CTL ATL and SHAM ATL animals spent a higher time in stage 1 compared to CTL and SHAM groups. Thus, CTL ATL animals also presented a higher number of stimulations in stage 5 compared to CTL animals. The stage 1 not observed in PX animals was present in PX ATL. Consequently, the number of stimulations required to reach stage 5 was statistically higher for the PX ATL group in relation to the PX group. Our results demonstrate that the acceleration in the kindling development of pinealectomized animals can be reverted by physical exercise.

Molecular biology tools have been employed to investigate the participation of peptides in human temporal lobe epilepsy (TLE). Active polypeptides and their receptors have been related to several brain processes, such as inflammation, apoptosis, brain development, K(+) and Ca(2+) channels' activation, cellular growth, and induction of neuronal differentiation. Previous works have shown a neuroprotector effect for kinin B2 receptor and a deleterious, pro-epileptogenic action for kinin B1 receptor in animal models of TLE. The present work was delineated to analyze the kinin B1 and B2 receptors expression in the hippocampus of patients presenting refractory mesial TLE. The hippocampi were removed during the patients surgery in a procedure used for seizure control and compared with tissues obtained after autopsy. Nissl staining was performed to study the tissue morphology and immunohistochemistry, and Western blot was used to compare the distribution and levels of both receptors in the hippocampus. In addition, real time PCR was employed to analyze the gene expression of these receptors. Nissl staining showed sclerotic hippocampi with hilar, granular, and pyramidal cell loss in TLE patients. Immunohistochemistry and Western blot analyses showed increased expression of kinin B1 and B2 receptors but the real-time PCR data demonstrated increased mRNA level only for kinin B2 receptors, when compared with controls. These data show for the first time a relationship between human TLE and the kallikrein-kinin system, confirming ours previous results, obtained from experimental models of epilepsy.

The effect of glycemic state on status epilepticus (SE) development was studied in animals of different ages, submitted to pilocarpine model of epilepsy. Groups: I- Rats with 9-day-old (P9): IA. Submitted to 1SE; IB. Saline-treated; IC. Induced- hyperglycemia; ID. Induced- hyperglycemia+SE; II- Rats submitted to three consecutive episodes of SE at P7, P8 and P9; III- Rats submitted to 1SE at P17; IV- Rats submitted to 1SE at P21. Hippocampal cell death and the expression of glucose transporter GLUT3 were analyzed in group I. The results demonstrated normoglycemia in the groups IA, IB and II, hypoglycemia in group III and hyperglycemia in group IV, showing that the glycemia during SE is age dependent. Induced hyperglycemia during SE in P9 protected the hippocampal neurons from death and both groups IC and ID presented increased GLUT3 expression, showing high glucose consumption by the hippocampus.

In the present study, newborn male Wistar rats were injected, subcutaneously, five times, every other day, with monosodium glutamate (MSG, 4 g/kg bw) or saline (as control, C), during the neonatal period. MSG animals developed destruction of the arcuate nuclei (ARC) with absence of NPY-immunoreactive cell bodies, which impaired both the food intake (baseline) and the 2-deoxy-D-glucose (2DG) glucoprivic feeding response. Increases in the immunoreactivity of corticotropin-releasing hormone-cell bodies in the paraventricular nuclei might have developed to compensate for the atrophy of the pituitary in MSG-treated rats. After systemic 2DG injection, neither the C nor the MSG rats increased their food intake, but they showed similar hyperglycemic responses, whereas plasma free fatty acids (FFA) increased only in the C group. In other groups, 2DG, norepinephrine (NE), neostigmine (NEO) and saline were intracerebroventricularly (i.c.v.) administered. In this condition, impairment of the hyperglycemic and food intake responses, associated to a lower increase in plasma FFA levels, were observed. As opposed to this, the MSG treatment gives support to NE effects, enhancing food intake, as well as plasma glucose and FFA levels. After NEO, plasma glucose increased only in the MSG group, while plasma FFA levels were elevated in the C rats. Taken together, the results obtained after MSG treatment point to a separate neural control of the hyperglycemic response and of the lipid mobilization when stimulated by central 2DG, NE or NEO administration. It seems likely that the excitatory neural pathway that controls lipid metabolism and is present in C rats was destroyed by the MSG treatment.

Mitochondrial abnormalities have been associated with several aspects of epileptogenesis, such as energy generation, control of cell death, neurotransmitter synthesis, and free radical (FR) production. Increased production of FRs may cause mtDNA damage leading to decreased activities of oxidative phosphorylation complexes containing mtDNA-encoded subunits. In this study, we investigated whether increased generation of FR during status epilepticus would be sufficient to provoke abnormalities in mtDNA and in the expression and activity of cytochrome c oxidase (CCO), complex IV of the respiratory chain, in the chronic phase of the pilocarpine model of temporal lobe epilepsy. DNA analysis revealed low amounts of a 4.8 kb mtDNA deletion but with no differences in frequency or quantity in the control and experimental groups. We did not find abnormalities in the expression and distribution of an mtDNA-encoded subunit of CCO (CCO-I) or a relative decrease in CCO-I when compared with nuclear-encoded subunits (CCO-IV and SDH-fp). No abnormality in CCO activity was observed through histochemistry. Although evidences of mitochondrial abnormalities were found in previously published studies, our results do not suggest that the FRs, generated during the acute phase, determined important abnormalities in mtDNA, in expression of CCO-I, and in CCO activity.

A considerable number of studies have demonstrated the anticonvulsant effect of melatonin. The present study examines the influence of pinealectomy on the amygdala kindling development in rats. Animals were divided into three groups: Pinealectomized rats (PNT) Sham rats (SHAM) and Control rats (CTL). The mean number of stimulations and the afterdischarge (AD) duration for each stage of kindling were similar among CTL and SHAM animals. Conversely, PNT animals showed particular characteristics during kindling development. They did not present stage 1 and spent a shorter time in stage 2 in relation to the CTL and SHAM animals. Consequently, the number of stimulations required to reach stage 5 was lower for the PNT group when compared to the CTL and SHAM groups. Besides, a longer AD duration during stage 5 in the PNT group was also observed. The present findings indicate that the pineal gland removal exert a significant influence on amygdala kindling development suggesting that melatonin holds potential interest in experimental therapy for epilepsy.

The aim of the present work was to analyze the effects of pinealectomy in the development of the epilepsy model induced by pilocarpine in adult male rats. Group I: Wistar male adult rats were submitted to pinealectomy, and 7 days after surgery, these animals received pilocarpine (350 mg/kg, i.p.) to induce three distinct behavioral phases: status epilepticus, seizure-free, and chronic phases. This late, as well as all control groups were continuously video-recorded for 60 days, to study behavior parameters. These animals were killed and the brain sections were processed for Nissl and neo-Timm. Group II: Another group, also submitted to pinealectomy, received several injections of melatonin (2.5 mg/kg): 20 min before, concomitantly with pilocarpine, 30 min, 1 h, and 2 h after pilocarpine administration. Some animals from group I and all from group II were sacrificed 48 h following status epilepticus onset to perform TUNEL assay. The latency for status epilepticus onset, status epilepticus length as well as mortality rate during status epilepticus were similar for pinealectomized and control groups. On the other hand, pinealectomized rats presented minor duration of the silent period, a higher number of spontaneous seizures during the chronic phase, increased number of TUNEL-positive cells (acute phase), increased neuronal loss, and marked supragranullar mossy fibers sprouting (chronic phase) in the hippocampal formation, when compared with control groups. Our data show that the pinealectomy facilitates the epileptogenic process that follows the long-lasting status epilepticus. This facilitation can be partially reverted by the simultaneous administration of melatonin.

This review examined critically studies issuing from the cognitive therapy (CT) model claiming to have unveiled cognitive causal factors of social phobia. Additionally, it examined outcome studies of CT-inspired interventions and other treatments having included measurements of cognitive constructs. Overall, we found no evidence consistently supporting the claim that social phobics are characterized by typical cognitive processes. Moreover, we found neither corroborating evidence for a controlling effect of such cognitive processes on social phobic conduct, nor consistent indications that cognitive therapies or techniques effect cognitive changes differently than other approaches. The evidence suggests rather, that cognitive factors change concurrently with other features of psychopathology as part of an overall improvement during or after effective therapy, regardless of therapeutic approach.

Kinins, a special class of polypeptides, are represented by bradykinin (BK), kallidin (Lys-BK), as well as their metabolites. The biological actions of these polypeptides binding on their receptors (B1 and B2) have been related to inflammation process, cytokines action, glutamate release and prostaglandins production. Usually, kinin B1 receptor is not expressed at a significant level under physiologic conditions in most tissues, but its expression is induced by injury, or upon exposure in vivo or in vitro to pro-inflammatory mediators. The kinin B2 receptor subtype is constitutively and widely expressed throughout the central and peripheral nervous system. These data raise the possibility for de novo expression of those receptors during the temporal lobe epilepsy (TLE), which has been related to cell death, gliosis and hippocampal reorganization. To correlate kinin system and TLE, adult male Wistar rats were submitted to pilocarpine model of epilepsy. The hippocampi were removed 6 h, 5 and 60 days after status epilepticus (SE) onset. The collected tissues were used to study the expression of kinin B1 and B2 mRNA receptors, using Real-Time PCR. Immunohistochemistry assay was also employed to visualize kinin B1 and B2 distribution in the hippocampus. The results show increased kinin B1 and B2 mRNA levels during acute, silent and chronic periods and changes in the kinin B1 and B2 receptors distribution. In addition, the immunoreactivity against kinin B1 receptor was increased mainly during the silent period, where neuron clusters of could be visualized. The kinin B2 receptor immunoreactivity also showed augmentation but mainly during the acute and silent periods. Our results suggest that kinin B1 and B2 receptors play an important role in the epileptic phenomena.

Background and Aims: No gold standard exists for nutritional screening/assessment. This cross-sectional study aimed to collect/use a comprehensive set of clinical, anthropometric, functional data, explore interrelations, and derive a feasible/sensitive/specific method to assess nutritional risk and status in hospital practice., Patients and Methods: 100 surgical patients were evaluated, 49M:51F, 55 +/- 18.9 (18-88) years. Nutritional risk assessment: Kondrup's Nutritional Risk Assessment, BAPEN's Malnutrition Screening Tool, Nutrition Screening Initiative, Admission Nutritional Screening Tool. Nutritional status: anthropometry categorised by Body Mass Index and McWhirter & Pennington criteria, recent weight loss > 10%, dynamometry, Subjective Global Assessment., Results: There was a strong agreement between all nutritional risk (k = 0.69-0.89, p < 0.05) and between all nutritional assessment methods (k = 0.51-0.88, p < or = 0.05) except for dynamometry. Weight loss > 10% was the only method that agreed with all tools (k = 0.86-0.94, p < or = 0.05), and was thereafter used as the standard. Kondrup's Nutritional Risk Assessment and Admission Nutritional Screening Tool were unspecific but highly sensitive (> or = 95%). Subjective Global Assessment was highly sensitive (100%) and specific (69%), and was the only method with a significant Youden value (0.7)., Conclusions: Kondrup's Nutritional Risk Assessment and Admission Nutritional Screening Tool emerged as sensitive screening methods; the former is simpler to use, Kondrup's Nutritional Risk Assessment has been devised to direct nutritional intervention. Recent unintentional weight loss > 10% is a simple method whereas Subjective Global Assessment identified high-risk/undernourished patients.

X11 alpha or Mint1 is a protein containing an N-terminal sequence, which binds to Munc-18 protein, a middle phosphotyrosine-binding domain (PTB) and two C-terminal PDZ (Post-synaptic density/Discs large/Zone Occludens-1) domains. The PDZ domains, which mediate protein-protein interactions have been shown to be involved in the organization of synaptic signaling pathways. Mint1 plays an important role in vesicle synaptic transport toward the active zone at the pre-synaptic site, and also participates in the transport of NR2B subunit of the NMDA receptor, to the post-synaptic site. To investigate the participation and distribution of this protein in the hippocampal subfield of rats submitted to the pilocarpine model of epilepsy, Mint1 was analyzed using Western blotting and immunohistochemistry. Animals of 5 h of status epilepticus showed decreased levels of this protein in the hippocampus when compared to the control animals. In contrast, animals from seizure-free period (silent group) and during spontaneous seizures phase (chronic group) showed increased Mint1 immunostaining in all hippocampal subfields, mainly in the dentate gyrus, when compared to the control group. The blotting confirmed the results obtained by immunohistochemistry. The present work suggests that Mint1 may be related to hippocampal plasticity during epileptogenesis in the pilocarpine model of temporal lobe epilepsy.

With the aim of evaluating nutrition indices and dialysis adequacy level in patients who started peritoneal dialysis (PD) without residual renal function, we retrospectively studied 19 patients [8 men, 11 women; 3 with diabetes (15.8%); mean age: 44.5 +/- 10.74 years; 15 on continuous ambulatory peritoneal dialysis (CAPD), 3 on continuous cycling peritoneal dialysis (CCPD), 1 on nightly intermittent peritoneal dialysis (NIPD)]. The mean time spent by these patients on hemodialysis before PD was 62.7 +/- 54.7 months (range: 8.8-216 months), and the mean time on PD was 46.2 +/- 21.4 months (range: 10-75 months). In these patients, we measured weekly Kt/V urea, weekly creatinine clearance (CrC), normalized protein catabolic rate (nPCR), body surface area (BSA), urea distribution volume (V), serum albumin, body mass index (BMI), percent lean body mass (%LBM), infusion volume (liters per day), subjective global assessment (SGA), and peritoneal equilibration test (PET). Using the Student t-test at a significance level of p < 0.05, we compared initial body weight (INW), actual weight (AW), and ideal body weight (IBW) according to age, sex, and height. We analyzed actuarial and technique survival (Kaplan-Meier). In regard to patient survival, only death was considered the end point; for technique survival, only technique failure was considered the end point. Data are expressed as mean +/- standard deviation. Results were: Kt/V, 2.20 +/- 0.46 L weekly; CrC, 59.11 +/- 12 L weekly; nPCR, 1.08 +/- 0.25 g/kg daily; BSA, 1.67 +/- 0.2 m2; V, 33.34 +/- 7.12; serum albumin, 3.68 +/- 0.22 g/dL; BMI, 24.06 +/- 4.16; %LBM, 64.92 +/- 10.13; SGA, 94.7% well-nourished; AW, 65.37 +/- 13.88 kg; IBW, 67.21 +/- 10.5 kg (AW vs IBW: r = 0.69, p > 0.05); INW, 61.54 +/- 11.07 kg (INW vs AW: r = 0.92, p < 0.05; INW vs IBW: r = 0.71, p < 0.05). Distribution of transport status by PET was 15.8% high transport, 36.8% high-average transport, 36.8% low-average transport, and 10.5% low transport. Mean infusion volume was 10.41 +/- 1.36 L in 24 hours. Cumulative survival was 100%, 98%, and 82% after 1, 2, and 6 years respectively. Technique survival was 100% after 6 years. The adequacy results accord with Dialysis Outcomes Quality Initiative (DOQI) recommendations, and the nutrition indices and actuarial and technique survival are satisfactory for anuric patients.

1. A simple HPLC method using sodium dodecyl sulfate (SDS) and electrochemical detection for the determination of norepinephrine (NE), 5-hydroxytyramine (DA) and 5-hydroxytryptamine (5-HT) in brain regions is described. 2. The tissue extraction procedure involved only two steps: protein precipitation with perchloric acid and pH adjustment to near 3.0. When used in combination with methanol as ion-pair in the mobile phase, sodium dodecyl sulfate effectively separated NE (6.6 min), epinephrine (EPI, 7.9 min), DA (14.3 min) and 5-HT (29.0 min) and the high methanol concentration used prevented the overlapping of the metabolites and monoamines in their chromatographic peaks. 3. The method was sensitive (40 to 70 pg of monoamine can be quantified) and reproducible and the values obtained for cortex, hippocampus, striatum and substantia nigra were consonant with most literature data.

The effects of amygdaloid kindled seizures during pregnancy on the concentrations of noradrenaline (NE), dopamine (DA) and serotonin (5HT) and of their respective metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5HIAA), have been studied in the cerebral cortex, brain stem and cerebellum of rat offspring at birth. The levels of DA and NE were increased and those of HVA and MHPG were not modified in the cortex. The levels of DA, NE, 5HT, MHPG and 5HIAA were increased in the cerebellum. The brain stem presented a decrease in DA and 5HT levels, but increased MHPG and HVA levels. It is suggested that, in order to investigate possible changes in the biogenic amine levels on the postnatal period, carefully planned prospective studies are needed.

Kainic acid (KA) is a powerful convulsant and neurotoxic agent. In the present paper the acute and long term effects of intrahippocampal KA administration on estrous cycle and on serum concentrations of progesterone were studied in adult female rats. Following KA injection, 3 distinct periods were observed: 1) acute period (24-48 h), 2) silent period (21-30 days), and 3) chronic period, characterized by the appearance of spontaneous recurrent seizures (30-45 days). KA administration did not affect progesterone levels during the acute period. In contrast, during the silent period, KA-treated animals exhibited irregular estrous cycling and decreased progesterone levels. These results are of interest in view of a possible link between epileptic phenomena and hormone secretion.

Spontaneous recurrent seizures (SRSs) were observed in female rats following the injection of kainic acid into the dorsal hippocampus. Pregnancy and nursing decreased the frequency of SRSs in such animals. The finding of a protective effect of pregnancy and lactation in this animal model of temporal lobe epilepsy stresses the usefulness of this model.

The effect of kainic acid (KA), a potent neurotoxic agent, on the renal function of rats was investigated. Intrahippocampal and intraperitoneal KA injections (2.5 micrograms and 8 mg/kg, respectively) led to a decrease in glomerular filtration rate and U/P inulin ratio with a concomitant increase in the amount of excreted Na+. However, acid excretion was maintained. These findings support the idea of a straight connection between neurohormonal secretion and renal function and may provide an interesting model to study renal hemodynamic changes induced by neurological disturbances.