Modulação do padrão convulsivo e das alterações cerebrais e comportamentais em crises epilépticas através do reposicionamento com mentantina

A crise epiléptica prolongada é acompanhada por neurodegeneração, alterações nos biomarcadores relacionados ao dano celular e prejuízos comportamentais, e os antiepilépticos clássicos geralmente não são eficazes em proteger contra estas consequências. O reposicionamento de fármacos, com foco em um medicamento com ação multialvo, é uma solução viável para lidar com a epilepsia refratária e pode fornecer uma alternativa para o gerenciamento das consequências indesejáveis das crises. Antagonistas do receptor de N-metil-D-aspartato exibem ação anticonvulsivante e atuam como neuroprotetores. No entanto, estes compostos demonstraram muitos efeitos adversos inaceitáveis. Apesar disso, a memantina (MN), um antagonista do NMDAR de baixa afinidade, é clinicamente bem tolerado e não produz efeitos colaterais consideráveis. Portanto, o objetivo da presente tese foi investigar o efeito protetor da MN contra a degeneração neuronal, padrão convulsivo, marcadores neuroquímicos e alterações comportamentais a longo prazo, induzidos por modelos químicos de crises prolongadas. Ratos Wistar filhotes receberam MN (20 mg / kg i.p.) em diferentes regimes de tratamento antes e após a indução da crise no modelo de LiCl-pilocarpina. A neurodegeneração foi quantificada por fluoro jade C 24 horas após a crise. Os peixeszebra foram pré-tratados com veículo ou MN (20 ou 50 mg / kg; i.p.) 1 h ou 2 h antes da imersão em solução de PTZ a 10 mM. As análises comportamentais e neuroquímicas foram realizadas 24 horas após a crise. Em CA1, a neurodegeneração diminuiu significativamente quando os ratos jovens receberam MN nos tempos de 0h e 0,25 h. Além disso, o pós-tratamento foi capaz de proteger contra a neurodegeneração na amigdala. O pré-tratamento com MN mostrou uma redução na morte celular no tálamo nos roedores. Já em peixe-zebra, a administração de MN reduziu a expressão relativa do gene grin2A. As crises induzidas com PTZ aumentam a carbonilação de proteínas e a atividade da SOD, e o tratamento com MN impediu essa alteração no estado redox. O peixe-zebra submetido às crises com PTZ apresentou aumento no tempo gasto na zona branca do aparato claro / escuro e a MN preveniu essa anormalidade comportamental. Nossos resultados demonstraram o efeito neuroprotetor da MN na morte neuronal induzida pelas crises no início da vida em ratos. Este efeito foi dependente do tempo e da região cerebral estudada. De fato, a ação anticonvulsivante da MN previne as alterações comportamentais e neuroquímicas relacionadas ao PTZ em peixe-zebra, reforçando o seu uso off-label para tratar as consequências neurocomportamentais da epilepsia.Prolonged epileptic seizure is accompanied by neurodegeneration, damage-related biomarkers alterations and impaired behavior, and the classical antiepileptic drugs are not effective in protect these consequences. Repurposing with focus in a multi-target drug is a viable solution to deal with refractory epilepsy and may provide an alternative for management of undesirable consequences of seizures. Typical N-methyl-D-aspartate receptor antagonists exhibit anticonvulsant action and are currently able to provide neuroprotection against neuronal death. However, these compounds have demonstrated many side effects. Despite this, memantine (MN), a low-affinity NMDA antagonist, is clinically well tolerate and does not induce considerable side effects. Therefore, the aim of the present thesis was to investigate the protectives effect of the MN against neuronal degeneration, seizures pattern, neurochemical seizure markers and long-term behavioral alterations induced by chemical models of prolonged seizures. Wistar pup rats received MN (20 mg/kg i.p.) at different treatment regimens before and after seizure induction in Li-pilocarpine model. Neurodegeneration was quantified by fluoro jade C staining. Zebrafish were pre-treated with vehicle or MN (20 or 50 mg/kg; i.p.) 1h or 2h before immersion into PTZ solution at 10 mM. Behavioral and neurochemical analyses was performed 24 h after seizure. In CA1 subfield neurodegeneration was significantly decreased when animals received MN at 0h and 0.25h post-treatment regimens. Additionally, post-treatment was able to protect against neurodegeneration in amygdala region. MN pre-treatment showed a reduction of cell death in thalamus. MN reduced the relative grin2A gene expression. PTZ-seizure induction increase protein carbonylation and SOD activity, and MN treatment prevented this state redox imbalance. PTZchallenged zebrafish presented increases in time spent in white zone into light/dark apparatus and MN prevented this behavioural abnormality. Our results demonstrated the neuroprotective effect of MN on neuronal loss induced by seizure early in life. This effect was time- and region-dependent. Indeed, anticonvulsant action of MN ameliorates behavioral and neurochemical PTZ-related changes in zebrafish seizure model, reinforcing the off-label use to treat neurobehavioral consequences of epilepsy

Spectrophotometric Determination of Aluminium with Salicylidene-o-aminophenol-4-sulfonic Acid

Salicylidene-o-aminophenol (SAPH), one of the typical Schiff base, has been studied as a spectrofluorimetric reagent for aluminium and also as a spectro-photometric reagent for copper, cadmium and zinc. As be expected from the structure, SAPH and its metal complexes are insoluble in water, then analytical difficulties result from the formation of the precipitates. Therefore, the methods such as precipitation followed by acid dissolution, solvent extraction or solubilization with quaternary ammonium salt are necessary for the determination. Salicylidene-o-aminophenol-4-sulfonic acid (SAPS), a SAPH derivative which introduced a sulfonic acid group into a phenyl ring, becomes soluble in water. It is available a simple and rapid determination of certain metals without any treatment. Morishige had reported the high sensitivity of SAPS on the fluorescence properties compared with 87 Schiff bases. Fluorimetry is more sensitive than spectrophotometry, but requires a instrumental necessity and skillfulness. The authors proposed the use of SAPS for the spectrophotometry in water solution, and determined copper and vanadium easily. This paper presents that SAPS as a spectrophotometric determination for aluminium and application to the determination of aluminium in steels

ダイ4キュウ アンモニウム エン ニヨル モリブデン 6 チロン サクタイ ノ チュウシュツ オヨビ コレオ リヨウ シタ モリブデン 6 ノ キュウコウ コウド テイリョウ

モリブデン(VI)-チロン錯体のゼフィラミン(tetradecyl dimethyl benzyl ammonium chloride)による抽出吸光光度定量法について検討した.弱酸性領域(pH4.6～7.6)でこの錯体は, 1,2-dichloroethaneに抽出され, 400nmに吸収極大を示す.モリブデン(VI)-チロンとの結合比は水溶液層では1 : 1であるが, 有機層中では1 : 2である.抽出によって, 感度は水溶液のそれよりかなりの増加がみとめられ, 最適条件での分子吸光係数は23.000,モリブデン(VI)濃度0～4.3×10^Mの範囲でベールの法則が成立することをみとめた.また, モリブデン(VI)-チロン-ゼフィラミン錯体の組成比は1 : 2 : 2であった.The extraction of molybdenum (VI)-Tiron complex with quaternary ammonium chloride has beeu investigated for the determination of molybdenum (VI). The complex extracted into 1,2-dichloroethane has an absorption maximum at 400 nm, with a constant absorption in the pH range from 4.6 to 7.6. The molar ratio of molybdenum (VI) to Tiron in the complex is estimated to be 1 to 1 for aqueous phase, and 1 to 2 for organic phase. By extracting into organic phase with tetradecyldimethyl ammonium chloride (Zep), the complex, Mo [(Tiron)_2(Zep)_2], whose molar absorptivity is 23,000 at 400nm is formed. Beer\u27s Law is obeyed within the limits of 0～4.3×10^M

Seizures induced by pentylenetetrazole in the adult zebrafish : a detailed behavioral characterization

Pentylenetetrazole (PTZ) is a common convulsant agent used in animal models to investigate the mechanisms of seizures. Although adult zebrafish have been recently used to study epileptic seizures, a thorough characterization of the PTZinduced seizures in this animal model is missing. The goal of this study was to perform a detailed temporal behavior profile characterization of PTZ-induced seizure in adult zebrafish. The behavioral profile during 20 min of PTZ immersion (5, 7.5, 10, and 15 mM) was characterized by stages defined as scores: (0) short swim, (1) increased swimming activity and high frequency of opercular movement, (2) erratic movements, (3) circular movements, (4) clonic seizure-like behavior, (5) fall to the bottom of the tank and tonic seizure-like behavior, (6) death. Animals exposed to distinct PTZ concentrations presented different seizure profiles, intensities and latencies to reach all scores. Only animals immersed into 15 mM PTZ showed an increased time to return to the normal behavior (score 0), after exposure. Total mortality rate at 10 and 15 mM were 33% and 50%, respectively. Considering all behavioral parameters, 5, 7.5, 10, and 15 mM PTZ, induced seizures with low, intermediate, and high severity, respectively. Pretreatment with diazepam (DZP) significantly attenuated seizure severity. Finally, the brain PTZ levels in adult zebrafish immersed into the chemoconvulsant solution at 5 and 10 mM were comparable to those described for the rodent model, with a peak after a 20-min of exposure. The PTZ brain levels observed after 2.5-min PTZ exposure and after 60-min removal from exposure were similar. Altogether, our results showed a detailed temporal behavioral characterization of a PTZ epileptic seizure model in adult zebrafish. These behavioral analyses and the simple method for PTZ quantification could be considered as important tools for future investigations and translational research

Avian Influenza A Virus (H5N1) Outbreaks, Kuwait, 2007

Phylogenetic analysis of influenza A viruses (H5N1) isolated from Kuwait in 2007 show that (H5N1) sublineage clade 2.2 viruses continue to spread across Europe, Africa, and the Middle East. Virus isolates were most closely related to isolates from central Asia and were likely vectored by migratory birds