Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

Performances neo-sirênicas: mitopoética, instinto caraíba e gaia ciência na canção popular

A presente tese problematiza a ideia defendida por Walter Benjamin (1892-1940) da perda da aura dos objetos artísticos na modernidade técnica, em sua reprodutibilidade, e defende que os cancionistas são neo-sereias modernas que carregam na performance vocal a gaia ciência nutrida pelo instinto caraíba de nossa cultura brasileira. Para tanto, numa metodologia majoritariamente interpretativa de canções populares, aliada ao método comparatista confrontando W. Benjamin, T. Adorno e Oswald de Andrade, entre outros pensadores , investiga: (1) a aplicação prática do conceito de mitopoética na re-criação e permanência do mito sirênico do mito como fonte de saber, a partir do arquétipo da sereia-mãe Iemanjá e suas derivações; (2) o conceito de metacanção, da canção como produto da neo-sereia e como subjetivação da linguagem; e (3) a distinção entre sujeito cancional e sujeito da canção, como artifícios artísticos neo-sirênicos assentados no Brasil

Influência das alterações imunes em gestantes infectadas pelo HIV-1 no perfil funcional das células T de neonatos não infectados

O número de mulheres jovens infectadas pelo HIV-1 vem crescendo desde o início da epidemia da aids, principalmente nos países em desenvolvimento, onde a frequência de gravidez é elevada. O desenvolvimento de estratégias para evitar a transmissão vertical tem aumentado o número de recém-nascidos não infectados nascidos de gestantes portadora do vírus. O objetivo da presente tese foi avaliar, in vivo e in vitro, o perfil de citocinas de neonatos não infectados, porém nascidos de mulheres infectadas pelo HIV-1. Os resultados demonstraram elevados níveis de citocinas pró-inflamatórias relacionadas ao fenótipo Th17, associadas à baixa produção de IL-10, tanto nos plasmas quanto nos sobrenadantes das culturas de células T ativadas obtidas do sangue do cordão umbilical de neonatos nascidos de gestantes infectadas pelo HIV-1 com cargas virais plasmáticas(PVL) detectáveis. De modo interessante, um perfil similar pró-inflamatório foi observado em amostras de sangue periférico de suas respectivas mães. Por outro lado, níveis elevados de IL-10, associados à reduzida produção de citocinas inflamatórias, foram dosados no sangue e nos sobrenadantes das culturas de células T ativadas de gestantes que controlavam a PVL, assim como de seus neonatos. Com relação à caracterização fenotípica das células T maternas produtoras de IL-10, a análise por citometria de fluxo demonstrou que essa citocina é majoritariamente produzida por células T CD4+Foxp3-. Curiosamente, a replicação viral in vitro do HIV-1 foi inferior nas culturas das gestantes infectadas pelo HIV-1 e foi relacionada aos efeitos inibitórios da IL-10 sobre a produção de TNF-α. Por fim, os neonatos não infectados expostosin utero à terapia antirretroviral (ART) apresentaram um menor peso ao nascer, e este achado foi inversamente correlacionado com os níveis periféricos maternos de TNF-α. Em conclusão, nossos achados sugerem que gestantes que conseguem controlar a PVL, e o incremento na produção de IL-10 materna possam favorecer a expansão das células Tr-1, as quais podem auxiliar em reduzir o risco de transmissão vertical do HIV-1 por reduzir a taxa de replicação viral. Por outro lado, outros resultados também apresentados aqui, apesar de preliminares, revelaram efeitos adversos da replicação viral e da ART em gestantes infectadas pelo HIV-1 no desenvolvimento funcional das células T de neonatos não infectados. Esses dados podem ajudar a explicar por que algumas dessas crianças apresentam elevado risco à morbidade e mortalidade devido a um estado basal de hipersensibilidade patológica.

Avaliação da resposta imune de neonatos não infectados pelo HIV-1 nascidos de gestantes soropositivas

A síndrome da imunodeficiência adquirida (AIDS), causada pelo vírus da imunodeficiência humana (HIV), é uma das mais destrutivas epidemias do mundo, e a infecção pelo HIV em mulheres jovens vem aumentando rapidamente nos dias atuais. Esse fato tem um impacto importante na transmissão vertical do vírus. Apesar da grande maioria dos casos de aids pediátrica em todo mundo resultar da transmissão vertical, aproximadamente dois terços das crianças expostas ao HIV durante a vida fetal não são infectadas pelo vírus. Muitos trabalhos sugerem que durante a gestação doenças infecciosas maternas podem ter consequências complexas para o desenvolvimento do feto, e poucos trabalhos têm explorado o impacto da exposição ao HIV sobre a responsividade imunológica de crianças não infectadas a diferentes estímulos, particularmente na era das drogas antirretrovirais. Portanto, esse trabalho teve como objetivo avaliar eventos imunes em neonatos não-infectados expostos ao HIV-1 nascidos de gestantes que controlam (G1) ou não (G2) a carga viral plasmática, usando neonatos não expostos como controle. Para tanto, sangue do cordão umbilical de cada neonato foi coletado, plasma e células mononucleares foram separados e a linfoproliferação e o perfil de citocinas foram avaliados. Os resultados demonstraram que a linfoproliferação in vitro induzido por ativadores policlonais foi maior nos neonatos do G2. Entretanto, nenhuma cultura de célula respondeu a um conjunto de peptídeos sintéticos do envelope do HIV-1. A dosagem de citocinas no plasma e nos sobrenadantes das culturas ativadas policlonalmente demonstrou que, enquanto a IL-4 e IL-10 foram as citocinas dominantes produzidas nos grupos G1 e controle, a secreção de IFN-γ, IL-1, Il-6, IL-17 e TNF-α foi significativamente superior nos neonatos G2. Níveis sistêmicos de IL-10 observados dentre os neonatos G1 foram maiores naqueles nascidos de mães tratadas com drogas inibidoras da transcriptase reversa do vírus. Por outro lado, níveis superiores de citocinas inflamatórias foram observados dentre estes nascidos de gestantes tratadas com terapia antirretroviral de alta eficácia. Em resumo, nossos resultados indicam uma responsividade imune alterada em neonatos expostos in utero ao HIV-1 e reforça o papel do tratamento materno anti-viral com drogas menos potentes em atenuar tais distúrbios.

Correlação entre a espessura da parede vesical e os achados urodinâmicos em pacientes com lesão medular traumática. Avaliação da influência das alterações morfológicas da bexiga nos resultados da injeção de toxina botulínica tipo-A no detrusor

Medir a espessura da parede vesical (EPV) através da ultrassonografia, correlacioná-la com os parâmetros urodinâmicos e avaliar o papel destes parâmetros para lesão do trato urinário superior. Avaliar também o papel das alterações da forma da bexiga nos resultados de injeção de toxina botulínica tipo-A (BTX-A) no detrusor em pacientes com lesão medular traumática (LMT). Trata-se de dois estudos. O primeiro é um estudo transversal de 272 pacientes com LMT submetidos à ultrassonografia renal e de bexiga e estudo urodinâmico. A parede anterior da bexiga foi medida e comparada com os dados urodinâmicos. A cistografia foi realizada em 57 pacientes. O segundo foi um estudo prospectivo avaliando os resultados da injeção de BTX-A no detrusor em 27 pacientes considerando os achados urodinâmicos (pré e pós procedimento) e as deformidades da bexiga (cistografia). A média da EPV foi de 3,94 mm e foi estatisticamente maior em pacientes com hiperatividade detrusora neurogênica associada à dissinergia vesicoesfincteriana (HDN/DVE), em comparação com aqueles sem DVE (p<0,001). Essa média também foi maior em pacientes com complacência < 20 mL/cmH2O, comparada aos pacientes com complacência ≥ 20 mL/cmH2O (p<0,001). A média da pressão detrusora máxima (Pdet Max) foi estatisticamente maior nos pacientes com refluxo vesicoureteral (RVU) em comparação com aqueles sem RVU (100,7 vs 61,2 cmH2O respectivamente, p=0,022). Pacientes com complacência < 20 mL/cmH2O apresentaram prevalência de hidronefrose 4,2 vezes maior, comparada aos pacientes com complacência ≥ 20 mL/cmH2O. Não houve associação estatística entre EPV e hidronefrose ou RVU. Vinte e sete pacientes foram submetidos à injeção de BTX-A no detrusor. A média de tempo de continência urinária foi de 8 meses. Nove pacientes (33,3%) tinham forma vesical alterada e 8 casos (29,6%) tinham divertículos. A capacidade cistométrica máxima, Pdet max, volume reflexo e complacência não apresentaram diferença significativa na presença de divertículos ou alteração da forma. O aumento da EPV está associado à complacência < 20 mL/cmH2O e HDN/DVE em pacientes com LMT. No entanto, não houve relação entre a EPV e hidronefrose ou RVU. Baixa complacência e HDN/DVE são os principais fatores de risco para dano ao trato urinário superior. A presença de divertículos ou alteração da forma vesical não influenciou nos resultados após injeção de BTX-A no detrusor.

Modeling the development of pronunciation in infant speech acquisition.

Pronunciation is an important part of speech acquisition, but little attention has been given to the mechanism or mechanisms by which it develops. Speech sound qualities, for example, have just been assumed to develop by simple imitation. In most accounts this is then assumed to be by acoustic matching, with the infant comparing his output to that of his caregiver. There are theoretical and empirical problems with both of these assumptions, and we present a computational model- Elija-that does not learn to pronounce speech sounds this way. Elija starts by exploring the sound making capabilities of his vocal apparatus. Then he uses the natural responses he gets from a caregiver to learn equivalence relations between his vocal actions and his caregiver's speech. We show that Elija progresses from a babbling stage to learning the names of objects. This demonstrates the viability of a non-imitative mechanism in learning to pronounce.

Differential expression of the Brunol/CELF family genes during Xenopus laevis early development

The BRUNOL/CELF family of RNA-binding proteins plays important roles in post-transcriptional regulation and has been implicated in several developmental processes. In this study, we describe the cloning and expression patterns of five Brunol genes in Xenopus laevis. Among them, only Brunol2 is maternally expressed and the zygotic expression of the other four Brunol genes starts at different developmental stages. During Xenopus development, Brunol1, 4-5 are exclusively expressed in the nervous system including domains in the brain, spinal cord, optic and otic vesicles. Brunol2 and 3 are expressed in both the somatic mesoderm and the nervous system. Brunol2 is also extensively expressed in the lens. In transfected Hela cells, BRUNOL1, 2 and 3 proteins are localized in both the cytoplasm and the nucleus, while BRUNOL4 and 5 are only present in the cytoplasm, indicating their different functions.

Effect of electric stimulation on heart beat and body muscle in fish

The effect of AC and DC electric stimulations on the heart-rate and the entire body of Heteropneustis fossillis, Tilapia mossambica and Macrobrachium rosenbergii were studied and presented in kymograph tracings. The reaction of spinal cord in Puntius ticto, Heteropneustis fossilis and Tilapia mossambica to D. C. field was observed to find out its role in electric shocks. A test-check of the electrical resistance of a few species was also conducted. The effect of D. C. and A.C. on the body muscle was found to be the same as that in the case of frog. Different degrees of cardiac slowing were observed in AC and DC. Unbalanced galvanotropic movements were also noticed in spinal fishes.

Caudal neurosecretory system of four hill stream fishes of India

Caudal neurosecretory system is an additional neuroendocrine system found in fishes. Great variation has been observed among different groups of fishes, so far its organization is concerned. Much work has been undertaken on the caudal neurosecretory system of elasmobranchs and teleosts. Large size scattered Dahlgren cells in the posterior end of spinal cord, corresponding to last few vertebrae, with long running axon process and a neurohaemal organ the urophysis are the characteristic features of the system. Although thoroughly investigated in fresh water carps, no work is reported in hill-stream fishes. In an attempt to investigate structure and organization of caudal neurosecretory system in hill-stream fishes, present investigation was undertaken in four hill-stream fish of Indian freshwater namely, Barilius bendelensis, Garra gotyla, Schizothorax plagiostomus and Tor tor. The organization of this system in hill-stream fishes was found to be quite different from that observed in fresh water carps. It displays an organization which is more close to the organization of caudal neurosecretory system observed in elasmobranchs. The features are described and discussed.

Lentivirus介导神经营养因子- 3促进脊髓损伤大鼠功能恢复

　目的　探讨Lentivirus介导分泌神经营养因子- 3 (NT - 3)直接体内转基因治疗大鼠脊髓损伤作用和机制。　方法　将28只Wistar大鼠在T10水平制成半横断损伤模型,随机分为体内转基因治疗组和损伤对照组,每组14只;用携带NT - 3和绿色荧光蛋白(GFP)的Lentivirus对大鼠行直接体内转基因治疗;荧光显微镜观察体内转基因表达,后肢运动功能评分法(BBB评分) 检测大鼠后肢功能恢复情况。　结果　用荧光显微镜检测到损伤脊髓内有较多的持续表达转基因的细胞; BBB评分结果显示,从伤后第4周开始,实验组大鼠后肢功能较对照组明显恢复( P < 0. 01) ,至第10周时,实验组和对照组BBB分差增大,达3. 3分。　结论　Lentivirus是一种有效的转基因载体,由Lentivirus介导分泌NT - 3的直接体内转基因治疗能够明显促进损伤脊髓的功能恢复。

人胚神经干细胞移植治疗大鼠脊髓损伤

　目的　探讨人胚神经干细胞( hNSC) 移植治疗脊髓损伤(SCI) 的可行性。方法　分 离、培养和鉴定hNSC;用5 溴22 脱氧尿苷嘧啶(BrdU) 标记hNSC ,并将其移植到14 只T10 半横断 的Wistar 大鼠损伤脊髓内(另外14 只T10 半横断损伤的大鼠作为对照组,仅损伤脊髓内注射 DMEM/ F12 培养液) ,用BrdU 的FITC 免疫荧光染色检测移植细胞的存活和迁徙,用NF2200 、 GFAP 免疫组织化学鉴定移植细胞的分化,BBB 评分评定大鼠功能恢复情况。结果　(1) 获得了大 量的hNSC; (2) 用免疫组织化学可以检测到移植的hNSC 能在体内长时间存活(达2 个月) 并向远 处迁徙,并分化为神经元和胶质细胞; (3) 检测到实验组大鼠BBB 得分明显高于对照组大鼠( P < 0. 01) ,在SCI 后第10 周时实验组和对照组BBB 得分最大差距达到2. 1分。结论　hNSC 移植能促 进SCI 大鼠后肢功能恢复,它是SCI 移植治疗较有价值的细胞资源。

Mechanisms of H+ modulation of glycinergic response in rat sacral dorsal commissural neurons

Many ionotropic receptors are modulated by extracellular H+. So far, few studies have directly addressed the role of such modulation at synapses. In the present study, we investigated the effects of changes in extracellular pH on glycinergic miniature inhibitory postsynaptic currents (mIPSCs) as well as glycine-evoked currents (I-Gly) in mechanically dissociated spinal neurons with native synaptic boutons preserved. H+ modulated both the mIPSCs and I-Gly, biphasically, although it activated an amiloride-sensitive inward current by itself. Decreasing extracellular pH reversibly inhibited the amplitude of the mIPSCs and I-Gly, while increasing external pH reversibly potentiated these parameters. Blockade of acid-sensing ion channels (ASICs) with amiloride, the selective antagonist of ASICs, or decreasing intracellular pH did not alter the modulatory effect of H+ on either mIPSCs or I-Gly, H+ shifted the EC50 of the glycine concentration-response curve from 49.3 +/- 5.7 muM at external pH 7.4 to 131.5 +/- 8.1 muM at pH 5.5, without altering the Cl- selectivity of the glycine receptor (GlyR), the Hill coefficient and the maximal I-Gly, suggesting a competitive inhibition of I-Gly by H+. Both Zn2+ and H+ inhibited I-Gly. However, H+ induced no further inhibition of I-Gly in the presence of a saturating concentration of Zn2+. In addition, H+ significantly affected the kinetics of glycinergic mIPSCs and I-Gly. It is proposed that H+ and/or Zn2+ compete with glycine binding and inhibit the amplitude of glycinergic mIPSCs and I-Gly. Moreover, binding of H+ induces a global conformational change in GlyR, which closes the GlyR Cl- channel and results in the acceleration of the seeming desensitization of IGly as well as speeding up the decay time constant of glycinergic mIPSCs. However, the deprotonation rate is faster than the unbinding rate of glycine from the GlyR, leading to reactivation of the undesensitized GlyR after washout of agonist and the appearance of a rebound I-Gly. H+ also modulated the glycine cotransmitter, GABA-activated current (I-GABA). Taken together, the results support a 'conformational coupling' model for H+ modulation of the GlyR and suggest that W may act as a novel modulator for inhibitory neurotransmission in the mammalian spinal cord.

Marine Vertebrates and Low Frequency Sound: Technical Report for LFA EIS

Over the past 50 years, economic and technological developments have dramatically increased the human contribution to ambient noise in the ocean. The dominant frequencies of most human-made noise in the ocean is in the low-frequency range (defined as sound energy below 1000Hz), and low-frequency sound (LFS) may travel great distances in the ocean due to the unique propagation characteristics of the deep ocean (Munk et al. 1989). For example, in the Northern Hemisphere oceans low-frequency ambient noise levels have increased by as much as 10 dB during the period from 1950 to 1975 (Urick 1986; review by NRC 1994). Shipping is the overwhelmingly dominant source of low-frequency manmade noise in the ocean, but other sources of manmade LFS including sounds from oil and gas industrial development and production activities (seismic exploration, construction work, drilling, production platforms), and scientific research (e.g., acoustic tomography and thermography, underwater communication). The SURTASS LFA system is an additional source of human-produced LFS in the ocean, contributing sound energy in the 100-500 Hz band. When considering a document that addresses the potential effects of a low-frequency sound source on the marine environment, it is important to focus upon those species that are the most likely to be affected. Important criteria are: 1) the physics of sound as it relates to biological organisms; 2) the nature of the exposure (i.e. duration, frequency, and intensity); and 3) the geographic region in which the sound source will be operated (which, when considered with the distribution of the organisms will determine which species will be exposed). The goal in this section of the LFA/EIS is to examine the status, distribution, abundance, reproduction, foraging behavior, vocal behavior, and known impacts of human activity of those species may be impacted by LFA operations. To focus our efforts, we have examined species that may be physically affected and are found in the region where the LFA source will be operated. The large-scale geographic location of species in relation to the sound source can be determined from the distribution of each species. However, the physical ability for the organism to be impacted depends upon the nature of the sound source (i.e. explosive, impulsive, or non-impulsive); and the acoustic properties of the medium (i.e. seawater) and the organism. Non-impulsive sound is comprised of the movement of particles in a medium. Motion is imparted by a vibrating object (diaphragm of a speaker, vocal chords, etc.). Due to the proximity of the particles in the medium, this motion is transmitted from particle to particle in waves away from the sound source. Because the particle motion is along the same axis as the propagating wave, the waves are longitudinal. Particles move away from then back towards the vibrating source, creating areas of compression (high pressure) and areas of rarefaction (low pressure). As the motion is transferred from one particle to the next, the sound propagates away from the sound source. Wavelength is the distance from one pressure peak to the next. Frequency is the number of waves passing per unit time (Hz). Sound velocity (not to be confused with particle velocity) is the impedance is loosely equivalent to the resistance of a medium to the passage of sound waves (technically it is the ratio of acoustic pressure to particle velocity). A high impedance means that acoustic particle velocity is small for a given pressure (low impedance the opposite). When a sound strikes a boundary between media of different impedances, both reflection and refraction, and a transfer of energy can occur. The intensity of the reflection is a function of the intensity of the sound wave and the impedances of the two media. Two key factors in determining the potential for damage due to a sound source are the intensity of the sound wave and the impedance difference between the two media (impedance mis-match). The bodies of the vast majority of organisms in the ocean (particularly phytoplankton and zooplankton) have similar sound impedence values to that of seawater. As a result, the potential for sound damage is low; organisms are effectively transparent to the sound – it passes through them without transferring damage-causing energy. Due to the considerations above, we have undertaken a detailed analysis of species which met the following criteria: 1) Is the species capable of being physically affected by LFS? Are acoustic impedence mis-matches large enough to enable LFS to have a physical affect or allow the species to sense LFS? 2) Does the proposed SURTASS LFA geographical sphere of acoustic influence overlap the distribution of the species? Species that did not meet the above criteria were excluded from consideration. For example, phytoplankton and zooplankton species lack acoustic impedance mis-matches at low frequencies to expect them to be physically affected SURTASS LFA. Vertebrates are the organisms that fit these criteria and we have accordingly focused our analysis of the affected environment on these vertebrate groups in the world’s oceans: fishes, reptiles, seabirds, pinnipeds, cetaceans, pinnipeds, mustelids, sirenians (Table 1).

Amolops bellulus: A new species of stream-breeding frog from western Yunnan, China (Anura : Ranidae)

We describe a new species of stream-breeding frog of the genus Amolops, Amolops bellulus, from the mountainous region of Lushui County, Yunnan Province, China, near the boundary between Yunnan and Myanmar. This species differs from all its congeners in a combination of morphological characteristics including the absence of a circummarginal groove at the tip of first finger, lack of a supratympanic fold, a white band along the upper jaw extending to shoulder, a black band starting from tip of snout along upper loreal region and extending to anterior flank of body, absence of a vocal sac, tympanum distinct and feebly concave, and the presence of vomerine teeth.

Murine MyaK, a member of a family of yeast YAK1-related genes, is highly expressed in hormonally modulated epithelia in the reproductive system and in the embryonic central nervous system

We have cloned a mouse homologue (designated Myak) of the yeast protein kinase YAK1. The 1210 aa open reading frame contains a putative protein kinase domain, nuclear localization sequences and PEST sequences. Myak appears to be a member of a growing family of YAK1-related genes that include Drosophila and human Minibrain as well as a recently identified rat gene ANPK that encode a steroid hormone receptor interacting protein. RNA blot analysis revealed that Myak is expressed at low levels ubiquitously but at high levels in reproductive tissues, including testis, epididymis, ovary, uterus, and mammary gland, as well as in brain and kidney. In situ hybridization analysis on selected tissues revealed that Myak is particularly abundant in the hormonally modulated epithelia of the epididymis, mammary gland, and uterus, in round spermatids in the testis, and in the corpora lutea in the ovary, Myak is also highly expressed in the aqueduct of the adult brain and in the brain and spinal cord of day 12.5 embryos, Mol. Reprod. Dev. 55:372-378, 2000. (C) 2000 Wiley-Liss, Inc.