Preliminary study of the inhibitory effect of selective M4 muscarinic receptor antagonist MT3 on form deprivation myopia in guinea pigs / 中国实验动物学报

Objective To evaluate the inhibitory effect of highly selective M4 receptor antagonist MT3 on the form deprivation myopia in guinea pigs and its potential mechanism. Methods Thirty?two healthy male guinea pigs were ran?domly divided into three groups:control group, form deprivation group, and form deprivation + MT3 group, 8 animals in each group. Refraction was measured by retinoscopy after cycloplegia before and after the experiment. The ocular biological dimensions were measured by A?scan ultrasound. RT?PCR was used to detect the relative expression of TGF?β2 mRNA in the retina and choroid. Results Compared with the right eyes of control group, the right eyes of form deprivation + MT3 group developed relative myopia of -1?44 ± 0?50 D (right?left eye) (P =0?001). The vitreous chamber depth and axial length of the right eyes were significantly prolonged by 0?10 ± 0?02 mm and 0?14 ± 0?07 mm (P<0?001, P<0?001), respectively, but the increases of myopia and axial length were significantly smaller than that of the form deprivation group (P<0?001, P<0?001, P<0?001). Down?regulation of relative mRNA expression of TGF?β2 in retina and choroid was found in the form deprivation group (P<0?001, P =0?014) compared with the right eyes of the control group, while up?regulation of relative mRNA expression of TGF?β2 in retina and choroid was found in the form deprivation + MT3 group ( P<0?001, P<0?001). Conclusions MT3 can inhibit the development of form deprivation myopia in guinea pigs, which may play an important role by the regulation of TGF?β2 mRNA level in the retina and choroid.

Modelagem do transporte de cloreto proveniente de esgoto urbano em um aquífero sedimentar usando MT3D: o caso da bateria de poços de Juazeiro do Norte (CE) / Modeling of transport of chloride in a sedimentary aquifer using MT3D: the case of a well field in Juazeiro do Norte (CE)

Esse trabalho consiste em um estudo de caso, em que o modelo de transporte de soluto MT3D, associado ao modelo de fluxo MODFLOW, foi utilizado na avaliação da contaminação de um aquífero por água superficial de um riacho contaminado com esgoto urbano, utilizando o cloreto como traçador. Nessa área, as águas do aquífero são explotadas por uma bateria de poços alinhada ao riacho. A calibração do modelo de transporte foi executada para reproduzir os teores de cloretos observados nas águas dos poços em campanhas de monitoramento. Já a do modelo de fluxo procurou reproduzir as cargas hidráulicas observadas durante testes de bombeamentos realizados em cada poço. Os resultados obtidos nessas calibrações foram compatíveis com as observações. A partir dos modelos calibrados, foi realizada uma simulação futura (prognóstico), visando determinar o tempo necessário para a recuperação da qualidade de água subterrânea após interrupção do lançamento de esgoto no riacho. Os resultados da modelagem indicaram que: os rebaixamentos produzidos pelo bombeamento dos poços são maiores nas proximidades do riacho; o transporte de contaminante ocorre, predominantemente, na vertical, induzido pelo bombeamento dos poços e pela recarga do aquífero a partir do riacho; os níveis de cloretos relativamente elevados nas águas dos poços podem voltar aos valores naturais do aquífero em aproximadamente um ano, caso o lançamento de esgoto no riacho seja interrompido. Assim, para evitar um maior comprometimento dos aquíferos da área por poluição persistente, o esgoto deverá ter um destino adequado e a área de preservação permanente do riacho deverá ser respeitada.

This paper presents a case study in which the solute transport model MT3D, associated with the MODFLOW flow model, was used in the assessment of contamination of an aquifer by surface water from a creek contaminated with urban wastewater, using chloride as a tracer. In that area of the aquifer, groundwater is exploited through a field of wells along the creek. The calibration of the transport model was implemented in order to reproduce the levels of chloride in water from wells observed in monitoring campaigns. The flow model sought to reproduce the hydraulic loads observed during pumping tests conducted in each well. The results obtained from these calibrations were consistent with observations. Based on the calibrated models, we carried out a "future simulation" (prognosis), in order to determine the time required for recovery of groundwater quality after stopping sewage discharge into the creek. Modeling results indicate that: drawdowns produced by pumping the wells are higher in the proximity of the creek; contaminant transport occurs, predominantly, vertically induced by pumping of the wells and by aquifer recharge from the creek; elevated levels of chloride in the waters from the wells may return to natural values in about one year, if the release of sewage into the creek is stopped. In this context, in order to prevent further damage to the aquifer area through persistent pollution, sewage must have a suitable destination and the area of permanent protection of the creek must be respected.

Metallothionein 3 attenuated the apoptosis of neurons in the CA1 region of the hippocampus in the senescence-accelerated mouse/PRONE8 (SAMP8) / Metalotioneina 3 atenuou a apoptose dos neurônios da região CA1 do hipocampo em camundongos PRONE8 com envelhecimento acelerado (SAMP8)

OBJECTIVE: Metallothionein 3 (MT-3) has been shown to protect against apoptotic neuronal death in the brains of patients with Alzheimer's disease. Zinc is a potent inhibitor of caspase-3 and its deficiency was found to promote apoptosis. Here, we measured the zinc and copper content in the brains of senescence-accelerated mouse/PRONE8 (SAMP8) and sought to investigate the effect of MT-3 on the apoptosis of neurons in the hippocampal CA1 region of these mice. METHOD: The zinc and copper content in the brain samples of SAMP8 and normal control SAMR1 mice were determined using an atomic absorption spectrophotometer. The mice were administered intraperitoneally for four weeks with MT-3 or MT1 and thereafter apoptosis was measured using the TUNEL method and the expression of anti-apoptotic protein Bcl-2 and proapoptotic protein Bax was examined by immunohistochemistry. RESULTS: Compared with that in SMAR1 mice, the content of zinc in the brains of SAMP8 mice was significantly reduced (P<0.05). Moreover, significant levels of apoptosis of neurons were observed in the hippocampus of SAMP8 mice, which, compared with those in SMAR1 mice, also showed significantly lower levels of Bcl-2 and higher levels of Bax (P<0.05). MT-3 increased zinc concentration in the hippocampus of SAMP8 mice and also significantly decreased apoptosis in these neurons dose-dependently and increased the levels of Bcl-2 and decreased the levels of Bax. CONCLUSION: MT-3 could attenuate apoptotic neuron death in the hippocampus of SAMP8, suggesting that the protein may lessen the development of neurodegeneration.

OBJETIVO: Metalotioneína 3 (MT-3) tem mostrado proteção contra a apoptose neuronal em cérebros de pacientes com doença de Alzheimer. Zinco é um potente inibidor da caspase-3, e sua deficiência pode promover a apoptose. No presente trabalho, foram dosados os níveis de zinco e cobre nos cérebros de camundongos PRONE8 com envelhecimento acelerado (SAMP8), visando investigar o efeito da MT-3 na apoptse dos neurônios da região hipocampal CA1 destes camundongos. MÉTODO: Os níveis de zinco e cobre em amostras cerebrais de camundongos SAMP8 e de controles normais SAMR1 foram determinados por absorção atômica em espectrofotometria. Foram administradas MT-3 ou MT-1 intraperitoneais durante quatro semanas, sendo em seguida avaliada a apoptose pelo método TUNEL , enquanto a expressão da proteína anti-apoptótica Bcl-2 e a proteína pró-apoptótica Bax foram avaliadas por imunohistoquímica. RESULTADOS: Em comparação aos camundongos SMAR1, o nível de zinco nas amostras cerebrais dos camundongos SAMP8 estava significativamente diminuído (P<0.05). Além disto, níveis significativos de apoptose foram observados no hipocampo dos camundongos SAMP8, o que, em comparação com os níveis em camundongos SMAR1, também mostrava níveis significativamente mais baixos de Bcl-2 e níveis mais altos de Bax (P<0.05). MT-3 aumentou a concentração de zinco no hipocampo dos camundongos SAMP8, além de diminuir significativamente a apoptose destes neurônios, de uma forma dose-dependente, ao mesmo tempo que aumentou níveis de Bcl-2 e diminuiu níveis de Bax. CONCLUSÃO: MT-3 pode atenuar a morte neuronal apoptótica no hipocampo de SAMP8, o que sugere que esta proteína possa diminuir a neurodegeneração.

The effects of mechanical stress on alkaline phosphatase activity of MC3T3-E1 cells / 대한치과교정학회지

Orthodontic force is a mechanical stress controlling both of tooth movement and skeletal growth. The mechanical stress stimulate bone cells that may exert some influence on bone remodeling. The purpose of this study was to evaluate the difference in cellular activity depending on mechanical stresses such as compressive and tensile force by determining the alkaline phosphatase(ALP) activity. A clonal osteogenic cell line MC3T3-E1 was seeded into a 24-well plate(2x 10(4)/well). At the confluent phase, a continuous compressive hydrostatic pressure(25g/cm2, 300g/cm2) and continuous tensile hydrostatic pressure( -25g/cm2, -300g/cm2) were applied for 4, 6, 10, 14, 18, 20 days respectively by a diaphgragm pump. At the end of the stimulation period, cell layers were prepared for ALP activity assay. The ALP activity of the compressive group increased more than that of the tensile group at same force magnitude, whereas the cells responded to a similar pattern regardless of the type of mechanical stress. The ALP activity of the compressive and tensile group turned into the level of the control group as the length of time increased. These results indicated that a mechanical stress may be more effective on cellular activity during active cellular proliferation and differentiation periods. The time to achieve maximum ALP activity was delayed as the mechanical stress increased in both the compressive and the tensile group. Accordingly, the magnitude of the stress rather than the type of mechanical stress may have more influence on cellular activity.