Severity and burden of partial-onset seizures in a phase III trial of eslicarbazepine acetate.

OBJECTIVE: The objective of this study was to compare posttreatment seizure severity in a phase III clinical trial of eslicarbazepine acetate (ESL) as adjunctive treatment of refractory partial-onset seizures. METHODS: The Seizure Severity Questionnaire (SSQ) was administered at baseline and posttreatment. The SSQ total score (TS) and component scores (frequency and helpfulness of warning signs before seizures [BS]; severity and bothersomeness of ictal movement and altered consciousness during seizures [DS]; cognitive, emotional, and physical aspects of postictal recovery after seizures [AS]; and overall severity and bothersomeness [SB]) were calculated for the per-protocol population. Analysis of covariance, adjusted for baseline scores, estimated differences in posttreatment least square means between treatment arms. RESULTS: Out of 547 per-protocol patients, 441 had valid SSQ TS both at baseline and posttreatment. Mean posttreatment TS for ESL 1200mg/day was significantly lower than that for placebo (2.68 vs 3.20, p<0.001), exceeding the minimal clinically important difference (MCID: 0.48). Mean DS, AS, and SB were also significantly lower with ESL 1200mg/day; differences in AS and SB exceeded the MCIDs. The TS, DS, AS, and SB were lower for ESL 800mg/day than for placebo; only SB was significant (p=0.013). For both ESL arms combined versus placebo, mean scores differed significantly for TS (p=0.006), DS (p=0.031), and SB (p=0.001). CONCLUSIONS: Therapeutic ESL doses led to clinically meaningful, dose-dependent reductions in seizure severity, as measured by SSQ scores. CLASSIFICATION OF EVIDENCE: This study presents Class I evidence that adjunctive ESL (800 and 1200mg/day) led to clinically meaningful, dose-dependent seizure severity reductions, measured by the SSQ.

Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G.C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G.C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response toa nutritional interventionwithMD.An intervention study ina high cardiovascular riskMediterranean population (314 men and 407 women) was undertaken. Participants were randomly assigned to consume a low-fat control diet or a MD supplementedwith virgin olive oil ornuts.Measureswereobtained at baseline and after a 3-mointervention period.At baseline, the COX-2 -765G.C polymorphismwas associated with lower serum IL-6 (5.85 6 4.82 in GG vs. 4.74 6 4.14 ng/L in C-allele carriers; P ¼ 0.002) and ICAM-1 (265.8 6 114.8 in GG vs. 243.0 6 107.1 mg/L in C-carriers; P ¼ 0.018) concentrations. These differences remained significant aftermultivariate adjustment. The IL-6 -174G.C polymorphism was associatedwith higher (CC vs. G-carriers) serumICAM-1concentrations in bothmenandwomenandwithhigherserumIL-6 concentrations inmen.Following the dietary intervention, no significant gene x diet interactions were found. In conclusion, although COX-2 -765G.C and IL-6 -174G.C polymorphismswere associatedwith inflammation, consuming aMD(either supplemented with virgin olive oil or nuts) reduced the concentration of inflammation markers regardless of these polymorphisms.

Iron metabolism and incidence of metabolic syndrome.

BACKGROUND AND AIMS: Whether iron metabolism affects metabolic syndrome (METS) is debated. We assessed the association between several markers of iron metabolism and incidence of METS. METHODS AND RESULTS: Data from 3271 participants (1870 women, 51.3 ± 10.4 years), free of METS at baseline and followed for 5.5 years. The association of serum iron, ferritin and transferrin with incident METS was assessed separately by gender. Incidence of METS was 22.6% in men and 16.5% in women (p < 0.001). After multivariate adjustment, a positive association was found between transferrin and incident METS in men: odds ratio (OR) and 95% confidence interval for the fourth relative to the first quartile 1.55 (1.04-2.31), p for trend = 0.03, while no association was found for iron OR = 0.81 (0.53-1.24), p for trend = 0.33 and ferritin OR = 1.30 (0.88-1.92), p for trend = 0.018. In women, a negative association was found between iron and incident METS: OR for the fourth relative to the first quartile 0.51 (0.33-0.80), p for trend<0.03; the association between transferrin and incident METS was borderline significant: OR = 1.45 (0.97-2.17), p for trend = 0.07 and no association was found for ferritin: OR = 1.11 (0.76-1.63), p for trend = 0.58. CONCLUSION: Transferrin, not ferritin, is independently associated with an increased risk of incident METS; the protective effect of iron in women should be further explored.

Relation entre l'alliance thérapeutique infirmière/patient, et les contrôles perçus par le patient en traitement de dépendances

Le but de cette étude était d'investiguer l'association entre l'alliance thérapeutique et le contrôle de substances, comme il est vécu par le patient. La théorie de King et le concept de l'alliance thérapeutique figuraient comme cadres théoriques. L'investigation se faisait à l'aide d'un questionnaire auto-administré, incluant l'instrument working alliance inventory (WAI) dans sa forme abréviée, traduit et validé en français, visant un échantillon de convenance (n=28). L'alliance thérapeutique était évaluée sur une échelle Likert à 12 questions, et les alliances thérapeutiques se sont révélées comme bonnes (x=61.68, max=84). Mais il y a une relation linéaire négative significative entre le degré à quel point les contrôles sont perçus comme pesants, évalués par une question supplémentaire sur une visual analog scale (VAS), et l'établissement d'une alliance thérapeutique (r =-0.67, p-value>0.001). De plus, la forme d'admission joue un rôle significatif, car dans cette étude, les patients admis sous pression de l'extérieur (n=7) ont de moins bonnes alliances (t, p-value=0.018) et vivent les contrôles comme plus pesants (Z, p-value=0.004) que les patients admis de leur propre gré (n=21). Malgré que ces résultats ne sont, vu le petit échantillon (n=28), pas généralisables, ils pourraient impliquer pour la pratique de repenser la prise d'urine et d'être sensibilisés aux conséquences possibles. Des options, comme l'introduction d'une supervision par caméra ou le retrait complet de l'infirmière de référence de toute sorte de contrôles, seraient imaginables. Au moins pour les personnes hospitalisées sous pression de l'extérieur et qui sont probablement, pour cette raison, plus susceptibles à tout dérangement de la relation.

Targeting iron-mediated retinal degeneration by local delivery of transferrin.

Iron is essential for retinal function but contributes to oxidative stress-mediated degeneration. Iron retinal homeostasis is highly regulated and transferrin (Tf), a potent iron chelator, is endogenously secreted by retinal cells. In this study, therapeutic potential of a local Tf delivery was evaluated in animal models of retinal degeneration. After intravitreal injection, Tf spread rapidly within the retina and accumulated in photoreceptors and retinal pigment epithelium, before reaching the blood circulation. Tf injected in the vitreous prior and, to a lesser extent, after light-induced retinal degeneration, efficiently protected the retina histology and function. We found an association between Tf treatment and the modulation of iron homeostasis resulting in a decrease of iron content and oxidative stress marker. The immunomodulation function of Tf could be seen through a reduction in macrophage/microglial activation as well as modulated inflammation responses. In a mouse model of hemochromatosis, Tf had the capacity to clear abnormal iron accumulation from retinas. And in the slow P23H rat model of retinal degeneration, a sustained release of Tf in the vitreous via non-viral gene therapy efficently slowed-down the photoreceptors death and preserved their function. These results clearly demonstrate the synergistic neuroprotective roles of Tf against retinal degeneration and allow identify Tf as an innovative and not toxic therapy for retinal diseases associated with oxidative stress.

Metabolic syndrome and nonalcoholic fatty liver disease: Is insulin resistance the link?

Metabolic syndrome (MetS) is a disease composed of different risk factors such as obesity, type 2 diabetes or dyslipidemia. The prevalence of this syndrome is increasing worldwide in parallel with the rise in obesity. Nonalcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease in western countries, affecting more than 30% of the general population. NAFLD encompasses a spectrum of liver manifestations ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), fibrosis and cirrhosis, which may ultimately progress to hepatocellular carcinoma. There is accumulating evidence supporting an association between NAFLD and MetS. Indeed, NAFLD is recognized as the liver manifestation of MetS. Insulin resistance is increasingly recognized as a key factor linking MetS and NAFLD. Insulin resistance is associated with excessive fat accumulation in ectopic tissues, such as the liver, and increased circulating free fatty acids, which can further promote inflammation and endoplasmic reticulum stress. This in turn aggravates and maintains the insulin resistant state, constituting a vicious cycle. Importantly, evidence shows that most of the patients developing NAFLD present at least one of the MetS traits. This review will define MetS and NAFLD, provide an overview of the common pathophysiological mechanisms linking MetS and NAFLD, and give a perspective regarding treatment of these ever growing metabolic diseases.

Effects of oral supplementation of iron on hepcidin blood concentrations among non-anaemic female blood donors: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Hepcidin is the main hormone that regulates iron balance. Its lowering favours digestive iron absorption in cases of iron deficiency or enhanced erythropoiesis. The careful dosage of this small peptide promises new diagnostic and therapeutic strategies. Its measurement is progressively being validated and now its clinical value must be explored in different physiological situations. Here, we evaluate hepcidin levels among premenopausal female donors with iron deficiency without anaemia. MATERIALS AND METHODS: In a preceding study, a 4-week oral iron treatment (80 mg/day) was administered in a randomized controlled trial (n = 145), in cases of iron deficiency without anaemia after a blood donation. We subsequently measured hepcidin at baseline and after 4 weeks of treatment, using mass spectrometry. RESULTS: Iron supplementation had a significant effect on plasma hepcidin compared to the placebo arm at 4 weeks [+0·29 nm [95% CI: 0·18 to 0·40]). There was a significant correlation between hepcidin and ferritin at baseline (R(2) = 0·121, P < 0·001) and after treatment (R(2) = 0·436, P < 0·001). Hepcidin levels at baseline were not predictive of concentration changes for ferritin or haemoglobin. However, hepcidin levels at 4 weeks were significantly higher (0·79 nm [95% CI: 0·53 to 1·05]) among ferritin responders. CONCLUSIONS: This study shows that a 4-week oral treatment of iron increased hepcidin blood concentrations in female blood donors with an initial ferritin concentration of less than 30 ng/ml. Apparently, hepcidin cannot serve as a predictor of response to iron treatment but might serve as a marker of the iron repletion needed for erythropoiesis.

Trajectory and predictors of quality of life in first episode psychotic mania.

BACKGROUND: Little is known about the trajectory of quality of life (QoL) following a first episode of psychotic mania in bipolar disorder (BD). This 18-month longitudinal study investigated the trajectory of QoL, and the influence of premorbid adjustment and symptoms on 18-month QoL in a cohort of young people experiencing a first episode of psychotic mania. METHODS: As part of an overarching clinical trial, at baseline, sixty participants presenting with a first episode of psychotic mania (BD Type 1 - DSM-IV) completed symptomatic and functional assessments in addition to the Premorbid Adjustment Scale - General Subscale. Symptom measures were repeated at 18-month follow up. QoL was rated using the Quality of Life Scale (QLS) at designated time points. RESULTS: Mean QLS scores at initial measurement (8 weeks) were 61% of the maximum possible score, increasing significantly to 70% at 12 months, and 71.2% at 18-month follow-up. Premorbid adjustment and 18-month depressive symptoms were significantly associated with QoL at 18-month follow-up. LIMITATIONS: Study limitations include the small sample size, inclusion of participants with psychotic mania only, use of measures originally designed for use with schizophrenia spectrum disorders, and lack of premorbid or baseline measurement of QoL. CONCLUSIONS: Results suggest that QoL can be maintained early in BD, and reinforce the importance of assertively treating depressive symptoms throughout the course of this disorder. The emergence of a link between premorbid adjustment and poorer QoL in this cohort highlights the importance of assessing facets of adjustment when planning psychological interventions.

Synthetic long peptide-based vaccine formulations for induction of cell mediated immunity: A comparative study of cationic liposomes and PLGA nanoparticles.

Nanoparticulate formulations for synthetic long peptide (SLP)-cancer vaccines as alternative to clinically used Montanide ISA 51- and squalene-based emulsions are investigated in this study. SLPs were loaded into TLR ligand-adjuvanted cationic liposomes and PLGA nanoparticles (NPs) to potentially induce cell-mediated immune responses. The liposomal and PLGA NP formulations were successfully loaded with up to four different compounds and were able to enhance antigen uptake by dendritic cells (DCs) and subsequent activation of T cells in vitro. Subcutaneous vaccination of mice with the different formulations showed that the SLP-loaded cationic liposomes were the most efficient for the induction of functional antigen-T cells in vivo, followed by PLGA NPs which were as potent as or even more than the Montanide and squalene emulsions. Moreover, after transfer of antigen-specific target cells in immunized mice, liposomes induced the highest in vivo killing capacity. These findings, considering also the inadequate safety profile of the currently clinically used adjuvant Montanide ISA-51, make these two particulate, biodegradable delivery systems promising candidates as delivery platforms for SLP-based immunotherapy of cancer.

Studium oeconomiae et historiae naturalis informatori necessarium, exhibens

Invocatio: I.N.S.S.T.

Simultaneous determination of moxifloxacin and H2 receptor antagonist in pharmaceutical dosage formulations by RP-HPLC: application to in vitro drug interactions

Simultaneous determination of moxifloxacin (MOX) and H2-antagonists was first time developed in bulk and formulations. Purospher STAR C18 (250 x 4.6 mm, 5 μm) column was used. The mobile phase (methanol: water: ACN, 60:45:5 v/v/v, pH 2.7) was delivered at a flow rate of 1.0 mL min-1, eluent was monitored at 236, 270 and 310 nm for cimetidine, famotidine and ranitidine, respectively. The proposed method is specific, accurate (98-103%), precise (intra-day and inter-day variation 0.098-1.970%) and linear (r>0.998). The LOD and LOQ were 0.006-0.018 and 0.019-0.005 μg mL-1, respectively. The statistical parameters were applied to verify the results. The method is applicable to routine analysis of formulations and interaction of MOX with H2-antagonist.

Conservação de Dimorphandra mollis benth. (fabaceae) baseada na estrutura genética de populações naturais

Dimorphandra mollis é uma espécie nativa do Cerrado com grande potencial econômico e tem sido alvo de intensa exploração, principalmente de seus frutos por causa do princípio ativo do composto rutina, importante para a produção de fármacos. Algumas propostas têm surgido para uma coleta controlada desses frutos, de forma a minimizar a perda de diversidade genética, entretanto existem poucas informações sobre aspectos ecológicos e genéticos da espécie. Nesse sentido, realizou-se o estudo da estrutura genética por meio de marcadores aloenzimáticos, visando dar subsídios a propostas de conservação de populações naturais de D. mollis. Dez locos polimórficos foram utilizados para estimar as frequências alélicas referentes a 180 indivíduos, distribuídos em três populações naturais (Campina Verde, Vargem da Cruz e Pau de Fruta) no Município de Jequitaí, Norte de Minas Gerais, Brasil. Os resultados indicam alta diversidade genética da espécie ( ou = 0,463), sendo pequena a variabilidade genética entre populações ( > ou = 0,025). Foi verificada ausência de endogamia dentro das populaçõe s( ou = -0,018 ( 0,007). O fluxo gênico estimado no conjunto das populações foi alto, com igual a 4,0, e suficiente para contrapor os efeitos da deriva genética. a alta diversidade genética nas populações da espécie indica potencial para a conservação genética in situ e também para o seu manejo. As estratégias de manejo da espécie devem considerar o tamanho efetivo populacional, no intuito de manter os níveis de variabilidade genética observados e a regeneração natural nas áreas. Palavras-chave: Fava d'anta, Marcadores aloenzimáticos e Variabilidade genética.

Fuel consumption of a tractor in function of wear, of ballasting and tire inflation pressure

When using appropriate inflation pressures and load capacity (ballast), it may obtain a higher yield and prolongation of the life of the tire, besides it may minimize the problems of loss of traction, increased slippage and fuel consumption. This study aimed to evaluate the fuel consumption of a tractor operating with new and worn tires in three conditions of ballasting and three inflation pressures, when driving on compacted soil with vegetation cover. The experiment was conducted at the experimental unit from the Department of Animal Science, Federal University of Lavras, state of Minas Gerais, Brazil, in an agricultural soil compacted by cattle trampling and with vegetation cover. It was used a tractor 4x2 with front wheel assist, of a 65.62 kW engine power. The tires were of R1 type, diagonal (front: 12.4 to 24; and rear: 18.4 to 30), the average height of the clutches of the new tires were 0.3 and 0.35 m for front and rear tires, respectively, and for the worn tires were 0.018 and 0.0045 m, for the front and the rear tires, respectively. The results showed advantages for the tractor equipped with new tires.