Protective effect of SRT1720 on acute liver injury induced by acetaminophen in mice and its mechanism / 中国生物制品学杂志

@#Objective To evaluate the protective effect of the activator of silent information regulator 2-related enzymes 1(SIRT1),SRT1720,on liver injury induced by acetaminophen(APAP)in mice and explore its mechanism. Methods Forty male C57BL/6J mice were randomly divided into normal control group,SRT1720 treatment group,APAP treatment group,and APAP + SRT1720 treatment group,with 10 mice in each group. Mice in SRT1720 and APAP + SRT1720 groups were given SRT1720(30 mg/kg body mass)by intragastric administration,while normal saline of equal volume was given by intragastric administration in control and APAP groups,once a day for 5 days;On the 6th day,mice in APAP and APAP + SRT1720 groups were injected i. p. with APAP(325 mg/kg body mass),while those in control and SRT1720 groups with equal volume of normal saline. After 24 hours,the peripheral blood was taken and the serum was separated,which were detected for the levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)by the corresponding kits;The liver tissue of mice was taken aseptically,observed for the pathological changes by HE staining,detected for the mRNA transcription levels of GRP78,PERK,eIF2 α,ATF4 and CHOP genes related to PERK-eIF2α-CHOP signaling pathway by RT-qPCR and detected for the relative expression levels of these corresponding proteins and Caspase12 protein by Western blot. Results Compared with normal control group,the serum ALT and AST levels of mice in APAP group significantly increased(t = 55. 21 and34. 29 respectively,each P < 0. 01);significant necrosis of hepatocytes was observed in liver tissue,the structure of hepatic lobules changed significantly,and the swelling and deformation of hepatocytes in some areas were serious;the mRNA transcription and relative protein expression levels of GRP78,PERK,eIFα,ATF4 and CHOP genes increased significantly(t = 9. 85～33. 89,each P < 0. 05)and the relative expression level of Caspase12 protein increased significantly(t = 11. 78,P < 0. 01). Compared with APAP group,the serum ALT and AST levels of mice in APAP + SRT1720 group decreased significantly(t = 42. 92 and 18. 02 respectively,each P < 0. 01);the degree of hepatocyte injury was obviously reduced and the number of swollen and deformed cells also significantly decreased;the mRNA transcription and relative protein expression levels of GRP78,PERK,eIF2α,ATF4 and CHOP decreased significantly(t = 6. 19～22. 43,each P < 0. 05)and the expression level of Caspase12 protein showed no significant decrease(t = 0. 34,P > 0. 05). Conclusion SRT1720improved APAP-induced liver injury in mice,possibly by inhibiting PERK-eIF2α-CHOP signaling pathway in endoplasmic reticulum stress(ERS).

Valores normativos de condición física en escolares argentinos de la provincia de Neuquén: estudio Plan de Evaluación de la Condición Física / Physical fitness standards in students from the province of Neuquén, Argentina. Physical Fitness Assessment Plan study

Introducción. Actualmente, se desconocen las características de la condición física (CF) en niños y adolescentes escolares de la provincia de Neuquén. Por eso, desde la Secretaría de Deporte de dicha provincia, se desarrolló el Plan de Evaluación de la Condición Física. El principal propósito del estudio fue aplicar la batería ALPHA-Fitness en escolares neuquinos, con el objetivo de construir tablas normativas de referencia de la CF.Población y métodos. 4487 alumnos neuquinos de ambos sexos, de entre 9 y 18,9 años de edad, fueron evaluados con la batería ALPHA-Fitnessde alta prioridad en 4 componentes de la CF: 1) Morfológico: peso corporal y estatura para calcular el índice de masa corporal; 2) Muscular: salto en largo sin carrera previa; 3) Motor: 4 x 10 m para evaluar la velocidad/agilidad; y 4) Cardiorrespiratorio: test de ida y vuelta en 20 m (20 m-SRT; por shuttle run test).Resultados. El índice de masa corporal medio obtenido fue 22,9 ± 4,7 kg/m2; se clasificó el 25 % en la categoría sobrepeso, y el 12,7 %, en obesidad. Los valores medios obtenidos para la CF fueron componente cardiorrespiratorio: 4,3 ± 2,5 etapas, 10,1 ± 1,2 km/h, volumen de oxígeno máximo de 38,7 ± 6,7 ml/kg/min; salto en largo: 147,3 ± 34,6 cm; motor: 13,0 ± 1,5 s. Los sujetos masculinos tuvieron mayor rendimiento en las pruebas de CF (p < 0,001).Conclusión. Los resultados de este estudio proveen las primeras tablas normativas de CF en niños y adolescentes de ambos sexos para la provincia de Neuquén, Argentina.

Introduction. At present, there is no information about the physical fitness (PF) of children and adolescents attending school in the province of Neuquén. The provincial Department of Sports developed the Physical Fitness Assessment Plan. The main objective of this study was to administer the ALPHA-Fitness test battery to the students of Neuquén in order to develop PF reference standards.Population and methods. A total of 4487 male and female students of Neuquén aged 9-18.9 years were assessed based on four PF components of the high priority ALPHA-Fitness test battery: 1) morphological: body weight and height to estimate body mass index; 2) musculoskeletal: standing long jump test; 3) motor: 4 x 10 m speed/agility test; and 4) cardiorespiratory: 20-m shuttle run test (SRT).Results. The mean body mass index was 22.9 ± 4.7 kg/m2; 25 % of participants were overweight and 12.7 %, obese. The mean values for the cardiorespiratory component were 4.3 ± 2.5 stages, 10.1 ± 1.2 km/h, maximal oxygen volume of 38.7 ± 6.7 mL/kg/min; standing long jump: 147.3 ± 34.6 cm; and for the motor component:13.0 ± 1.5 s. Male participants had a better performance in PF tests (p < 0.001).Conclusion. The study results provide the first PF standards for male and female children and adolescents of the province of Neuquén, Argentina.

Influence of SRT1720 on apoptosis ofhigh glucose-induced mouse mesangial cells / 中国药理学通报

Aim To investigate the effect of Sirt1 activator SRT1720 on high glucose(HG)-induced apoptosis in mouse mesangial cells(MMCs).Methods Cultured mouse MMCs were divided into normal glucose group(NG),NG plus mannitol group(M),high glucose group(HG),HG plus SRT1720 group(HG+SRT).Apoptosis of MMCs was analyzed by DeadEndTM Fluorometric TUNEL System and flow cytometry.Reactive oxygen species(ROS)production was observed by flow cytometry.The expression levels of caspase-3,cleaved caspase-3,Bax,Bcl-2,p38 MAPK,p-p38 MAPK,p53,acetylated p53 and cytochrome C protein were observed by Western blot.The mRNA levels of Bax and Bcl-2 were detected by real-time PCR.Results Compared with normal glucose group,the production of ROS,the number of cell apoptosis,the expression of cleaved caspase-3,p-p38 MAPK and acetylated p53 and ratio of Bax/Bcl-2 were significantly increased,the expression of Sirt1 was decreased,meanwhile,the release of cytochrome C from mitochondria to cytoplasm was significantly increased in MMCs in high glucose group.Treatment with SRT1720 inhibited HG-induced increase of ROS production,cell apoptosis,expression of cleaved caspase-3,acetylated p53 and p-p38 MAPK,ratio of Bax/Bcl-2 and release of cytochrome C,and reversed HG-induced Sirt1 expression.Conclusion SRT1720 could prevent HG-induced apoptosis maybe by decreasing ROS production,preserving mitochondrial function and inhibiting p53 acetylation and activation of p38 MAPK in MMCs.

Independent Life Skills among psychosocial care network users of Rio Grande do Sul, Brazil / Habilidades de Vida Independente de usuários da rede de atenção psicossocial do Rio Grande do Sul, Brasil

Abstract This is a cross-sectional study that aims to identify the prevalence of lower independent living skills and their associations in 390 users of psychiatric community-based services in the state Rio Grande do Sul, Brazil. For tracing the outcome it was used the “scale Independent Living Skills Survey”, adopting a cut-off value lower than 2. The crude and adjusted analyses were conducted on binary logistic regressions and they considered a hierarchical model developed through a systematic literature review. In adjusted analysis the level of the same variables were adjusted to each other and to previous levels. The statistical significance remained as a < 0.05 p-value. The prevalence of smaller independent living skills was 33% and their associations were: younger age; no partner; lower education; resident at SRT; diagnosis of schizophrenia and younger diagnosis.

Resumo Este estudo transversal objetiva identificar a prevalência de menores habilidades de vida independente e suas associações em 390 usuários de serviços comunitários de saúde mental no estado do Rio Grande do Sul, Brasil. Para delimitar o desfecho, a escala “Independent Living Skills Survey” foi utilizada adotando-se como ponto de corte valores menores que 2. Análises brutas e ajustadas foram conduzidas por regressão logística binária que considerou um modelo teórico hierarquizado desenvolvido a partir de uma revisão sistemática de literatura. Na análise ajustada as variáveis do mesmo nível foram ajustadas entre si e com as do nível anterior. Significância estatística foi considerada como p-valor < 0,05. A prevalência de menores habilidades de vida independente foi de 33% e suas associações foram: menor idade; não possuir companheiro; menor escolaridade; residência no SRT; diagnóstico de esquizofrenia e menor tempo de diagnóstico.

Noise Induced Hearing Loss in Hard Rock Miners of Kadapa, A.P. India.

Background: Noise is excessive, unwanted sound stimulus in the atmosphere produced by extraneous sources resulting in permanent pathological changes in the inner ear, the cochlear nerve and its ganglia. It is one of the constituents of atmospheric pollution. Noise in the vicinity of workplaces is termed as occupational noise trauma which is imminent in workers in certain industries and unavoidable in them, but preventable to some extent. The present study is to measure such audiological threshold values to correlate the pathological changes in the workers with the help of audiometry. The aim of the study is to measure the noise levels in the industry and its effect on hearing capabilities of miners working there with audiological data and to formulate effective preventive measure for them. Methods: Miners from a Hard Rock cutting industry near Kadapa, A.P. are chosen and divided into 2 groups depending upon their work experience between 3 to 14 years. Audiometry is performed to record their Air Conduction thresholds in both ears at all the frequencies, before and after working hours. The data are analyzed and looked for statistical significance. Results: Miners with less than 7 years work experience had smaller temporary threshold shifts compared to miners above 7 years experience. The base level A.C threshold values were higher compared to miners with less than 7 years experience. The threshold shift was mostly observed in the frequency 6000KHZ, in both the ears. The average of mean thresholds of Air Conduction was found to be higher in the higher frequencies. Conclusion: Prolonged exposure to noise levels above 85dB for 8 hours in a day, 6 days per week for 3 to 14 years results in hearing loss due to permanent changes in the inner ear. Higher frequencies are more affected than the lower frequencies with higher base level thresholds. All the frequencies showed temporary threshold shifts ranging from 1.69 to 4.37dB when recorded immediately after the working periods. There was statistical significance observed for all frequencies in both ears for the threshold shifts with a P value less than 0.05.

Inhibitory effects of SRT1720 on the apoptosis of rabbit chondrocytes by activating SIRT1 via p53/bax and NF-κB/PGC-1α pathways / 华中科技大学学报（医学）（英德文版）

SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 μmol/L SRT1720 groups and blank control group (0 μmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis. The expression levels of SIRT1, p53, NF-κB/p65, Bax, and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) were detected by Western blotting and the expression levels of SIRT1, type II collagen, and aggrecan mRNA by RT-PCR. The results showed that in the SRT1720-treated groups, the nuclei of chondrocytes were morphologically intact and had uniform chromatin. In the blank control group, nuclear rupture into debris was observed in chondrocytes. With the SRT1720 concentration increasing, the chondrocyte viability increased, the apoptosis rate decreased, the protein expression levels of SIRT1 and PGC-1α and the mRNA expression levels of type II collagen and aggrecan increased ({ptP}<0.05), and the expression levels of p53, NF-κB and bax decreased (P<0.05). It was suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways.

SIRT1 negatively regulates amyloid-beta-induced inflammation via the NF-B pathway

Chronic inflammation induced by amyloid-beta (Aβ) plays a key role in the development of age-related macular degeneration (AMD), and matrix metalloproteinase-9 (MMP-9), interleukin (IL)-6, and IL-8 may be associated with chronic inflammation in AMD. Sirtuin 1 (SIRT1) regulates inflammation via inhibition of nuclear factor-kappa B (NF-κB) signaling, and resveratrol has been reported to prevent Aβ-induced retinal degeneration; therefore, we investigated whether this action was mediated via activation of SIRT1 signaling. Human adult retinal pigment epithelial (RPE) cells were exposed to Aβ, and overactivation and knockdown of SIRT1 were performed to investigate whether SIRT1 is required for abrogating Aβ-induced inflammation. We found that Aβ-induced RPE barrier disruption and expression of IL-6, IL-8, and MMP-9 were abrogated by the SIRT1 activator SRT1720, whereas alterations induced by Aβ in SIRT1-silenced RPE cells were not attenuated by SRT1720. In addition, SRT1720 inhibited Aβ-mediated NF-κB activation and decrease of the NF-κB inhibitor, IκBα. Our findings suggest a protective role for SIRT1 signaling in Aβ-dependent retinal degeneration and inflammation in AMD.

Clinical research of SRT and 3D-CRT on treatment of brain metastasis form lung cancer / 重庆医学

Objective To assess the evaluation of SRT (Stereotactic radiotherapy ) and 3D-CRT (Three-dimensional conformal ra-diotherapy)on treatment of brain metastasis from lung cancer .Methods From June 2009 to June 2011 ,74 patients with multiple brain metastasis(brain metastasis ≤3 ,tumor mass ≤3 cm) from lung cancer were analyzed retrospectively ,37 patients received 3D-CRT alone were retrospectively compared with 37 patients who received SRT alone .the results was evaluated by median survival time(MS) ,local control(LC) and toxicity effect .Results The median survival time(MS) was 9 .3 ,which 8 .6 months after 3D-CRT ,and 10 .6 months after SRT .the local control rate was 73 .5% for 3D-CRT ,and 79 .6% for SRT after 3 months .there was no difference between two groups on toxicity effect from stastic .Conclusion The SRT was a efficacious methods for the treatment of brain metastasis from lung cancer ,which could improve the local control rate ,but there was no more toxiticy .

Signal-to-noise Ratio Loss in the People with Normal Audiograms / 听力学及言语疾病杂志

Objective To explore the signal-to-noise ratio loss (SNR loss) of the people with normal pure-tone audiograms .Methods A group of 10 patients were recruited into the study ,who complained they could not hear speech clearly in the real world environment but had normal pure-tone audiograms ,immittance and word rec-ognition score (WRS) results .The Mandarin hearing in noise test (M-HINT ) was administered to them and the results were compared to the normal ranges published in the journal .Results All of them had SNR loss when noise (speech spectrum) came from front of them ,but 9 patients had SNR loss when noise came from 90 degree left or 90 degree right of them .Conclusion The current study showed the patients had speech hearing loss in the noisy envi-ronment ,regardless of whether they had normal audiograms ,immittance and WRS results .So we should pay atten-tion to such patients and adopt some special tests (eg M-HINT) .It is better for us to communicate and counsel with them .

Purification and characterization of extracellular lipase from a new strain: Pseudomonas aeruginosa SRT 9 / Purificação e caracterização de uma lipase extracelular produzida por uma nova cepa: Pseudomonas aeruginosa SRT9

An extra cellular lipase was isolated and purified from the culture broth of Pseudomonas aeruginosa SRT 9 to apparent homogeneity using ammonium sulfate precipitation followed by chromatographic techniques on phenyl Sepharose CL- 4B and Mono Q HR 5/5 column, resulting in a purification factor of 98 fold with specific activity of 12307.8 U/mg. The molecular weight of the purified lipase was estimated by SDS-PAGE to be 29 kDa with isoelectric point of 4.5. Maximum lipase activity was observed in a wide range of temperature and pH values with optimum temperature of 55ºC and pH 6.9. The lipase preferably acted on triacylglycerols of long chain (C14-C16) fatty acids. The lipase was inhibited strongly by EDTA suggesting the enzyme might be metalloprotein. SDS and metal ions such as Hg2+, Zn2+, Cu2+, Ag2+ and Fe2+ decreased the lipase activity remarkedly. Its marked stability and activity in organic solvents suggest that this lipase is highly suitable as a biotechnological tool with a variety of applications including organo synthetic reactions and preparation of enantiomerically pure pharmaceuticals. The Km and Vmax value of the purified enzyme for triolein hydrolysis were calculated to be 1.11 mmol/L and 0.05 mmol/L/minrespectively.

Uma lipase extracelular foi isolada e purificada a partir de um caldo de cultura de Pseudomonas aeruginosa SRT9 até homogeneidade visível empregando-se precipitação com sulfato de amônia, seguida de técnicas cromatográficas em colunas de fenil sefarose CL-4B e Mono Q HR 5/5, obtendo-se um fator de purificação de 98 vezes, e atividade especifica de 12307,8 U/mg. Por SDS_PAGE, estimou-se que o peso molecular da lipase purificada é 29kDa, com um ponto isoelétrico de 4,5. A lipase apresentou atividade máxima em uma ampla faixa de temperatura e pH, com ótimos a 55ºC e pH 6,9. A lípase foi mais ativa sobre triacilglicerois de cadeia longa (C14-C16). A lipase foi fortemente inibida por EDTA, o que sugere que a enzima pode ser uma metaloproteína. SDS e íons metálicos, como Hg2+, Zn2+,Cu2+, Ag2+ e Fe2+, diminuíram marcadamente a atividade da lipase. Sua grande estabilidade e atividade em solventes organicos sugerem que esta lípase pode ser uma excelente ferramenta tecnológica com várias aplicações como reações organosintéticas e preparação de produtos farmacêuticos enantiomericamente puros. Os valores de Km e Vmax para a enzima purificada na hidrólise de trioleina foram 1,11 mmol/L e 0,05 mmol/L/min, respectivamente.

Measurement of Speech Reception Threshold by Picture Identification in Young Children / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Young children response more readily to speech than to pure tone stimuli. Although there are several reports on modification of speech Reception Threshold Testing by picture identification in the States, none has been reported in Korea. MATERIALS AND METHODS: In this study, we investigated the testing of SRT-PI in 102 young children of normal development between 24 and 36 months. All subjects were tested not only with SRT-PI but also with play audiometry in the same condition. RESULTS: Overall success rate of SRT-PI was 80.3% while only 3.9% of subjects were successful in play audiometry. The success rate of SRT-PI was significantly higher in the 29-36 months group than in the 24-28 months group. Test time and threshold did not show significant differences between in sex and age of subjects with regard to SRT-PI. CONCLUSION: SRT-PI is a simple, efficient and very useful test battery for audiologic evaluation in young children.