ICV Global: perspectivas futuras

A iniciativa faz parte de parceria entre a Apex-Brasil e o GVces, em seu projeto ICV Global (inovação e sustentabilidade nas cadeias globais de valor)

ICV Global: fotomontagem

A iniciativa faz parte de parceria entre a Apex-Brasil e o GVces, em seu projeto ICV Global (inovação e sustentabilidade nas cadeias globais de valor)

Testosterone reinforcement : intravenous and intracerebroventricular self-administration in male rats and hamsters

Rationale: Anabolic steroids are drugs of abuse. However, the potential for addiction remains unclear. Testosterone induces conditioned place preference in rats and oral self-administration in hamsters. Objectives: To determine if male rats and hamsters consume testosterone by intravenous (IV) or intracerebroventricular (ICV) self- administration. Methods: With each nose-poke in the active hole during daily 4-h tests in an operant condi- tioning chamber, gonad-intact adult rats and hamsters received 50 mg testosterone in an aqueous solution of b-cyclodextrin via jugular cannula. The inactive nose- poke hole served as a control. Additional hamsters received vehicle infusions. Results: Rats (n=7) expressed a significant preference for the active nose-poke hole (10.0€2.8 responses/4 h) over the inactive hole (4.7€1.2 responses/4 h). Similarly, during 16 days of testosterone self-administration IV, hamsters (n=9) averaged 11.7€2.9 responses/4 h and 6.3€1.1 responses/4 h in the active and inactive nose-poke holes, respectively. By contrast, vehicle controls (n=8) failed to develop a preference for the active nose-poke hole (6.5€0.5 and 6.4€0.3 responses/4 h). Hamsters (n=8) also self-administered 1 mg testosterone ICV (active hole:39.8€6.0 nose-pokes/ 4 h; inactive hole: 22.6€7.1 nose-pokes/4 h). When testosterone was replaced with vehicle, nose-poking in the active hole declined from 31.1€7.6 to 11.9€3.2 responses/ 4 h within 6 days. Likewise, reversing active and inactive holes increased nose-poking in the previously inactive hole from 9.1€1.9 to 25.6€5.4 responses/4 h. However, reducing the testosterone dose from 1 mg to 0.2 mg per 1 ml injection did not change nose-poking. Conclu- sions: Compared with other drugs of abuse, testosterone reinforcement is modest. Nonetheless, these data support the hypothesis that testosterone is reinforcing.

Influence of martensite content and morphology on the toughness and fatigue behavior of high-martensite dual-phase steels

A series of high-martensite dual-phase (HMDP) steels exhibiting a 0.3 to 0.8 volume fraction of martensite (V m ), produced by intermediate quenching (IQ) of a vanadium and boron-containing microalloyed steel, have been studied for toughness and fatigue behavior to supplement the contents of a recent report by the present authors on the unusual tensile behavior of these steels. The studies included assessment of the quasi-static and dynamic fracture toughness and fatigue-crack growth (FCG) behavior of the developed steels. The experimental results show that the quasi-static fracturetoughness (K ICV ) increases with increasing V m in the range between V m =0.3 and 0.6 and then decreases, whereas the dynamic fracture-toughness parameters (K ID , K D , and J ID ) exhibit a significant increase in their magnitudes for steels containing 0.45 to 0.60 V m before achieving a saturation plateau. Both the quasi-static and dynamic fracture-toughness values exhibit the best range of toughnesses for specimens containing approximately equal amounts of precipitate-free ferrite and martensite in a refined microstructural state. The magnitudes of the fatigue threshold in HMDP steels, for V m between 0.55 and 0.60, appear to be superior to those of structural steels of a similar strength level. The Paris-law exponents (m) for the developed HMDP steels increase with increasing V m , with an attendant decrease in the pre-exponential factor (C).

FTY720 attenuates excitotoxicity and neuroinflammation

Background: FTY720 (fingolimod, Gilenya(TM)), a structural analog of sphingosine-1-phosphate (S1P), is the first oral drug approved for treatment the relapsing-remitting form of multiple sclerosis (MS), and its efficacy has been related to induced lymphopenia and consequent immunosuppression via modulation of S1P(1) receptors (S1P(1)R). However, due to its lipophilic nature, FTY720 crosses the blood brain barrier (BBB) and could act directly on neural cells. In this study, we investigated the effectiveness of FTY720 as a neuroprotective agent using in vitro and in vivo models of excitotoxic neuronal death and examined if FTY720 exerts a direct action on neurons, or/and an indirect modulation of inflammation-mediated neurodegeneration as a possible mechanism of neuroprotection. Methods: Primary neuronal and organotypic cortical cultures were treated with N-methyl-D-aspartic acid (NMDA) to induce excitotoxic cell death (measured by lactate dehydrogenase (LDH) assay or propidium iodide uptake, respectively). The effects of FTY720 treatment (10, 100 and 1,000 nM) on neuronal survival were examined. As an in vivo model of neuronal death and inflammation, we used intracerebroventricular (icv) administration of kainic acid (KA; 0.5 mu g/2 mu l) in Sprague-Dawley rats. FTY720 was applied icv (1 mu g/2 mu l), together with KA, plus intraperitoneally (ip; 1 mg/kg) 24 h before, and daily, until sacrifice 3 days after icv. Rats were evaluated for neurological score, neuronal loss in CA3 hippocampal region and activation of microglia at the lesion site. In addition, we tested FTY720 as a modulator of microglia responses using microglial cell cultures activated with lipopolysaccharide (LPS) and its effects in stress signalling pathways using western blotting for p38 and JNK1/2 mitogen-activated protein kinases (MAPKs). Results: FTY720 was able to reduce excitotoxic neuronal death in vitro. Moreover, in vivo repeated FTY720 administration attenuated KA-induced neurodegeneration and microgliosis at the CA3 lesion site. Furthermore, FTY720 negatively modulates p38 MAPK in LPS-activated microglia, whereas it had no effect on JNK1/2 activation. Conclusions: These data support a role for FTY720 as a neuroprotective agent against excitotoxin-induced neuronal death and as a negative modulator of neuroinflammation by targeting the p38 MAPK stress signalling pathway in microglia.

Dieta hiperlipídica materna, tecido adiposo, fígado, metabolismo de carboidratos e sinalização central de leptina na prole de camundongos C57BL/6

O consumo materno de dieta hiperlipídica saturada durante a gestação e lactação favorece o desenvolvimento obesidade e anormalidades metabólicas na prole. Este trabalho teve como objetivo testar a hipótese de que a prole proveniente de mães alimentadas com dieta hiperlipídica durante a gestação e lactação desenvolve obesidade e anormalidades metabólicas e de que essas alterações estão associadas a resistência central a leptina. As ratas grávidas da linhagem C57BL/6 (n=20) foram alimentadas com dieta standard chow (SC; 19% de lipídeos) ou dieta hiperlipídica (HF; 49% de lipídeos) durante todo período de gestação e lactação. Após o desmame, a prole de machos foi dividida em quatro grupos experimentais, de acordo com a dieta das mães e da prole: SC(mães)/SC(prole), SC/HF, HF/SC e HF/HF (n=12/gp). As características metabólicas foram avaliadas pela curva de ganho de peso; medida da pressão arterial; glicose de jejum, área sob a curva no teste oral de tolerância a glicose; concentrações de triglicerídeos hepáticos e estimativa da esteatose hepática; análise plasmática de insulina e leptina e; distribuição e análise morfológica do tecido adiposo. Para analisar a sensibilidade a leptina, os quatro grupos originais foram subdivididos em dois grupos cada (veículo ou leptina-5g) para verificar a resposta alimentar (g) após o tratamento agudo intracerebroventricular (ICV) e a sinalização hipotalâmica de leptina. A dieta HF durante o período pós-desmame (grupo SC/HF), durante gestação e lactação (grupo HF/SC), ou ambos os períodos (grupo HF/HF), promoveu aumento da massa corporal. No que concerne as alterações hepáticas e a ação da insulina, a dieta HF durante o período perinatal favoreceu 25% de esteatose hepática, hiperinsulinemia e hiperleptinemia, enquanto os demais grupos experimentais SC/HF e HF/HF, demonstraram um padrão mais exacerbado. A avaliação da distribuição e morfometria do tecido adiposo demonstra o importante papel da dieta HF perinatal em amplificar a habilidade de estocar gordura visceral na prole. Considerando a ação central da leptina nos grupos tratados, a resposta alimentar mostrou-se atenuada em SC/HF, indicando o efeito determinante da dieta pós-desmame sobre a ação da leptina nesse modelo. Os resultados indicam fortemente que a dieta HF materna afeta a saúde da prole adulta. Especificamente, a prole programada apresenta esteatose hepática, hipertrofia de adipócitos, aumento de gordura visceral, hiperleptinemia e resistência a insulina. Esse fenótipo não está associado a resistência central a leptina na prole aos três meses de idade.

去甲肾上腺素刺激高原鼠兔CRF的分泌

We studied the effect of neuro transmitter no repin ephrine (N E) on immuno reactive cortico trop inreleasing factor (CRF) of median eminence (M E) in the native pika (Ochotona cu rz oniae). At one hour after intra cerebrovent ricular ( icv) adm inistrat ion of N E in doses of 3.75,7.5, 15 and 30 μg/100 g BW , the CRF level ofM E increased. And the plasma cortico sterone concent rat ion also increased. Two and six days after adrenalectomy (ADX) , N E concent ration in hypothalamus declined to 76.32% and 76.27% of those in intact pika, plasma cortico rsterone concent ration also decreased to 16.57 and 2.05% of the control. These results indicated that N E have a effect on activating HPA axis through activating hypothalamic CRF in Ochotona curzoniae.

细胞因子对大鼠抑郁样行为的影响

Depression is one of the most important psychological diseases to threaten human health. “Cytokine theory of depression” suggests that cytokines may play an important role in depression, which provided a new perspective in the study the mechanism and the therapy of depressive symptoms. This view is supported by various findings. Administration of pro-inflammatory cytokine or lipoposaccharide in animal induces depressive-like behavior such as anhedonia and low locomotion, which is very similar to the behavioral symptoms of depression in humans. However, the earlier researches may only pay attention to the short-time behavior effects; the effects of long-time behavior changes have not been clearly reported. In addition, there are few reports about the effects of pro-inflammatory cytokine or anti-inflammatory cytokine on the depressive-like behavior induced by chronic stressors. To further understand the role of cytokines in depression, the purpose of the present study is to investigate the dose and time effects of pro-inflammatory cytokines induced by lipoposaccharide on depressive-like behavior, sensitization effect of pro-inflammatory and blockage effect of anti-inflammatory on depressive-like behavior induced by chronic cold swimming stress. The behavioral observation was carried out using sacharin preference test, open field test and elevated-plus maze. The results indicated that: 1) The activated immunity induced by LPS i.p administration could induce significant depressive-like behavior, but these behaviors had no long-term effect; 2)The depressive-like behaviors induced by stress could be elicited earlier and kept longer by the activated immunity induced by LPS ip ; 4) The chronic activated immunity induced by LPS icv administration could provoke significant depressive-like behavior, and the depressive-like behaviors induced by stress could be enhanced by icv LPS, LPS and stress had certain interact-sensitization effect on depressive-like behavior； 5) Anti-inflammatory cytokines IL-10 icv reversed the depressive-like behaviors induced by the stress. In conclusion, cytokines play an important role in the depressive-like behavior. Both peripheral and central administration of LPS induced a certain depressive-like behavior and enhanced stress-induced depressive behavior. The anti-inflammatory cytokine IL-10 icv could reverse the depressive-like behaviors induced by the stress. Keywords: lipoposaccharide, depressive-like behavior, anhedonia, locomotion, chronic cold swimming stress

A natural extension of the conventional finite volume method into polygonal unstructured meshes for CFD application.

A new general cell-centered solution procedure based upon the conventional control or finite volume (CV or FV) approach has been developed for numerical heat transfer and fluid flow which encompasses both structured and unstructured meshes for any kind of mixed polygon cell. Unlike conventional FV methods for structured and block structured meshes and both FV and FE methods for unstructured meshes, the irregular control volume (ICV) method does not require the shape of the element or cell to be predefined because it simply exploits the concept of fluxes across cell faces. That is, the ICV method enables meshes employing mixtures of triangular, quadrilateral, and any other higher order polygonal cells to be exploited using a single solution procedure. The ICV approach otherwise preserves all the desirable features of conventional FV procedures for a structured mesh; in the current implementation, collocation of variables at cell centers is used with a Rhie and Chow interpolation (to suppress pressure oscillation in the flow field) in the context of the SIMPLE pressure correction solution procedure. In fact all other FV structured mesh-based methods may be perceived as a subset of the ICV formulation. The new ICV formulation is benchmarked using two standard computational fluid dynamics (CFD) problems i.e., the moving lid cavity and the natural convection driven cavity. Both cases were solved with a variety of structured and unstructured meshes, the latter exploiting mixed polygonal cell meshes. The polygonal mesh experiments show a higher degree of accuracy for equivalent meshes (in nodal density terms) using triangular or quadrilateral cells; these results may be interpreted in a manner similar to the CUPID scheme used in structured meshes for reducing numerical diffusion for flows with changing direction.

Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background

The aggregation of beta-amyloid to plaques in the brain is one of the hallmarks of Alzheimer disease (AD). Numerous studies have tried to elucidate to what degree amyloid peptides play a role in the neurodegenerative developments seen in AD. While most studies report an effect of amyloid on neural activity and cognitive abilities of rodents, there have been many inconsistencies in the results. This study investigated to what degree the different genetic backgrounds affect the outcome of beta-amyloid fragment (25-35) on synaptic plasticity in vivo in the rat hippocampus. Two strains, Wistar and Lister hooded rats, were tested. In addition, the effects of a strong (600 stimuli) and a weak stimulation protocol (100 stimuli) on impairments of LTP were analysed. Furthermore, since the state of amyloid aggregation appears to play a role in the induction of toxic processes, it was tested by dual polarisation interferometry to what degree and at what speed beta-amyloid (25-35) can aggregate in vitro. It was found that 100 nmol beta-amyloid (25-35) injected icv did impair LTP in Wistar rats when using the weak but not the strong stimulation protocol (P <0.001). One-hundred nano mole of the reverse sequence amyloid (35-25) had no effect. LTP in Lister Hooded rats was not impaired by amyloid at any stimulation protocol. The aggregation studies showed that amyloid (25-35) aggregated within hours, while amyloid (35-25) did not. These results show that the genetic background and the stimulation protocol are important variables that greatly influence the experimental outcome. The fact that amyloid (25-35) aggregated quickly and showed neurophysiological effects, while amyloid (35-25) did not aggregate and did not show any effects indicates that the state of aggregation plays an important role in the physiological effects.