Validation of Housekeeping Genes in the Brains of Rats Submitted to Chronic Intermittent Hypoxia,a Sleep Apnea Model

Obstructive sleep apnea (OSA) is a syndrome characterized by intermittent nocturnal hypoxia, sleep fragmentation, hypercapnia and respiratory effort, and it has been associated with several complications, such as diabetes, hypertension and obesity. Quantitative real-time PCR has been performed in previous OSA-related studies; however, these studies were not validated using proper reference genes. We have examined the effects of chronic intermittent hypoxia (CIH), which is an experimental model mainly of cardiovascular consequences of OSA, on reference genes, including beta-actin, beta-2-microglobulin, glyceraldehyde-3-phosphate dehydrogenase, hypoxanthine guanine phosphoribosyl transferase and eukaryotic 18S rRNA, in different areas of the brain. All stability analyses were performed using the geNorm, Normfinder and BestKeeper software programs. With exception of the 18S rRNA, all of the evaluated genes were shown to be stable following CIH exposure. However, gene stability rankings were dependent on the area of the brain that was analyzed and varied according to the software that was used. This study demonstrated that CIH affects various brain structures differently. With the exception of the 18S rRNA, all of the tested genes are suitable for use as housekeeping genes in expression analyses.     

Prediction of Cardiovascular Events in Statin-Treated Stable Coronary Patients of the Treating to New Targets Randomized Controlled Trial by Lipid and Non-Lipid Biomarkers

Several plasma non-lipid biomarkers have been shown to predict major cardiovascular events (MCVEs) in population studies. Our objective was to investigate the relationship between lipid and non-lipid biomarkers levels achieved during statin therapy and the incidence of MCVEs in patients with stable coronary heart disease (CHD). We conducted a substudy of the TNT (Treating to New Targets) study, which was a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of CHD. Fasting plasma levels of standard lipids and of 18 non-lipid biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in 157 patients who experienced MCVEs during the 4.9 years of study follow-up and in 1349 controls. MCVE was defined as CHD death, nonfatal, non-procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke. After adjusting for age, sex and treatment arm, plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, high-sensitivity C-reactive protein (hsCRP), insulin, neopterin, N-terminal pro-brain natriuretic peptide (BNP), lipoprotein(a) [Lp(a)], and the soluble receptor for advanced glycation end products (sRAGE) were predictive of recurrent MCVEs (P≤0.02 for each doubling of plasma concentration). However, no significant association was observed between the risk of recurrent MCVEs and plasma levels of low-density lipoprotein cholesterol, adiponectin, cystatin C, lipoprotein-associated phospholipase A2, monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, osteopontin, soluble CD40 ligand, soluble intercellular adhesion molecule-1, or soluble vascular cell adhesion molecule-1. After further adjustment for diabetes, hypertension, smoking, and BMI, the relationship between hsCRP, insulin and MCVE were no longer significant, while the relationship between Lp(a), neopterin, NT-proBNP and sRAGE and MCVE remained statistically significant. In conclusion, in patients with CHD treated with atorvastatin, plasma levels of Lp(a), neopterin, NT-proBNP, and sRAGE are associated with the risk of recurrent MCVEs.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00327691","term_id":"NCT00327691"}}NCT00327691.     

The role of circulating serotonin in the development of chronic obstructive pulmonary disease

Background

Cigarette smoking is a major risk factor in the development of age-related chronic obstructive pulmonary disease (COPD). The serotonin transporter (SERT) gene polymorphism has been reported to be associated with COPD, and the degree of cigarette smoking has been shown to be a significant mediator in this relationship. The interrelation between circulating serotonin (5-hydroxytyptamine, 5-HT), cigarette smoking and COPD is however largely unknown. The current study aimed at investigating the mediation effects of plasma 5-HT on cigarette smoking-induced COPD and the relation between plasma 5-HT levels and age.

Methods

The association between plasma 5-HT, age and COPD was analyzed in a total of 62 COPD patients (ever-smokers) and 117 control subjects (healthy non-smokers and ever-smokers). Plasma 5-HT levels were measured by enzyme-linked immuno assay (EIA).

Results

The elevated plasma 5-HT levels were significantly associated with increased odds for COPD (OR = 1.221, 95% CI = 1.123 to 1.319, p<0.0001). The effect remained significant after being adjusted for age and pack-years smoked (OR = 1.271, 95% CI = 1.134 to 1.408, p = 0.0003). Furthermore, plasma 5-HT was found to mediate the relation between pack-years smoked and COPD. A positive correlation (r = 0.303, p = 0.017) was found between plasma 5-HT levels and age in COPD, but not in the control subjects (r = −0.149, p = 0.108).

Conclusion

Our results suggest that cigarette smoke-induced COPD is partially mediated by the plasma levels of 5-HT, and that these become elevated with increased age in COPD. The elevated plasma 5-HT levels in COPD might contribute to the pathogenesis of this disease.     

不同坡向人工油松幼林下地表苔藓植物层片的物种多样性与结构特征

调查和分析了岷江上游大沟流域的 4个坡向 (偏东坡N -E80°、偏西坡N -W 85°、偏南坡S -E10°、偏北坡N-W2 0°)人工油松 (Pinustabuliformis)林下地表苔藓植物的物种多样性、组成和结构特征。在 4个坡向的油松林下共发现 13种苔藓 ,各林下苔藓物种组成数量在 6 - 13种之间 ,并且具有较高的相似性。冰川青藓 (Brachytheci um glacile)、大羽藓 (Thuidiumcymbifolium)、厚角绢藓 (Entodonconcinnus)、密叶美喙藓 (Eurhynchiumsavatieri)、小酸土藓 (Oxysteguscuspidatus)和光萼苔 (Porellapinnata)为这 4个坡向油松林下的共有种 ,其中冰川青藓、大羽藓为优势物种。 4个坡向人工油松幼林下地表苔藓植物出现频率分别为 10 0 % (偏西、偏北油松林 )和 96 .7% (偏东、偏南油松林 ) ,其平均盖度、平均密度、平均厚度分别在 5 .5 0 %± 0 .90 %至 2 5 .6 6 %± 2 .76 %、4 80 .6 7± 133.6 5至 2 72 4 .80± 4 19.72株 /m2 和 4 .73± 0 .31至 6 .83± 0 .73mm之间。无论是苔藓植物层片的多样性指数还是结构参数 ,均以偏东坡向的油松林下为最低 ;而偏西坡向的油松林下除厚度略低于偏南坡向外 ,其他指标均最高。综合研究结果表明 ,坡向是形成苔藓植物物种多样性组成和结构差异的重要环境因素 ,对苔藓植物的生存     

Viral Load Levels Measured at Set-Point Have Risen Over the Last Decade of the HIV Epidemic in the Netherlands

Background

HIV-1 RNA plasma concentration at viral set-point is associated not only with disease outcome but also with the transmission dynamics of HIV-1. We investigated whether plasma HIV-1 RNA concentration and CD4 cell count at viral set-point have changed over time in the HIV epidemic in the Netherlands.

Methodology/Principal Findings

We selected 906 therapy-naïve patients with at least one plasma HIV-1 RNA concentration measured 9 to 27 months after estimated seroconversion. Changes in HIV-1 RNA and CD4 cell count at viral set-point over time were analysed using linear regression models. The ATHENA national observational cohort contributed all patients who seroconverted in or after 1996; the Amsterdam Cohort Studies (ACS) contributed seroconverters before 1996. The mean of the first HIV-1 RNA concentration measured 9–27 months after seroconversion was 4.30 log₁₀ copies/ml (95% CI 4.17–4.42) for seroconverters from 1984 through 1995 (n = 163); 4.27 (4.16–4.37) for seroconverters 1996–2002 (n = 232), and 4.59 (4.52–4.66) for seroconverters 2003–2007 (n = 511). Compared to patients seroconverting between 2003–2007, the adjusted mean HIV-1 RNA concentration at set-point was 0.28 log₁₀ copies/ml (95% CI 0.16–0.40; p<0.0001) and 0.26 (0.11–0.41; p = 0.0006) lower for those seroconverting between 1996–2002 and 1984–1995, respectively. Results were robust regardless of type of HIV-1 RNA assay, HIV-1 subtype, and interval between measurement and seroconversion. CD4 cell count at viral set-point declined over calendar time at approximately 5 cells/mm³/year.

Conclusion

The HIV-1 RNA plasma concentration at viral set-point has increased over the last decade of the HIV epidemic in the Netherlands. This is accompanied by a decreasing CD4 cell count over the period 1984–2007 and may have implications for both the course of the HIV infection and the epidemic.     

SHP2及其在乳腺癌发生发展中的作用

SHP2是一种非受体型蛋白酪氨酸磷酸酶,其介导的信号转导异常与多种疾病包括肿瘤的发生和发展密切相关,对SHP2的深入研究有助于对其作用机制的阐明以及潜在药物学靶点的发现。本文简要介绍了SHP2的结构、功能及其介导的Ras/ERK信号通路,并着重阐述了SHP2与乳腺癌发展的关系。     

Reliability of FEV1/FEV6 to Diagnose Airflow Obstruction Compared with FEV1/FVC: The PLATINO Longitudinal Study

QUESTION

A 6-second spirometry test is easier than full exhalations. We compared the reliability of the ratio of the Forced expiratory volume in 1 second/Forced expiratory volume in 6 seconds (FEV₁/FEV₆) to the ratio of the FEV₁/Forced vital capacity (FEV₁/FVC) for the detection of airway obstruction.

METHODS

The PLATINO population-based survey in individuals aged 40 years and over designed to estimate the prevalence of post-Bronchodilator airway obstruction repeated for the same study participants after 5–9 years in three Latin-American cities.

RESULTS

Using the FEV₁/FVC<Lower limit of normal (LLN) index, COPD prevalence apparently changed from 9.8 to 13.2% in Montevideo, from 9.7 to 6.0% in São Paulo and from 8.5 to 6.6% in Santiago, despite only slight declines in smoking prevalence (from 30.8% to 24.3%). These changes were associated with differences in Forced expiratory time (FET) between the two surveys. In contrast, by using the FEV₁/FEV₆ to define airway obstruction, the changes in prevalence were smaller: 9.7 to 10.6% in Montevideo, 8.6 to 9.0% in São Paulo, and 7.5 to 7.9% in Santiago. Changes in the prevalence of COPD with criteria based on FEV₁/FVC correlated strongly with changes in the FET of the tests (R² 0.92) unlike the prevalence based on a low FEV₁/FEV₆ (R² = 0.40).

CONCLUSION

The FEV₁/FEV₆ is a more reliable index than FEV₁/FVC because FVC varies with the duration of the forced exhalation. Reporting FET and FEV₁/FEV₆<LLN helps to understand differences in prevalence of COPD obtained from FEV₁/FVC-derived indices.     

Ocular Hypertension after Pediatric Cataract Surgery: Baseline Characteristics and First-Year Report

Monitoring intraocular pressure (IOP) is essential for pediatric cataract treatment but always difficult due to lack of cooperation in young children. We present the baseline characteristics and the first-year results of a long-term prospective cohort study, which are aimed to determine the relationship of the incidence of ocular hypertension (OH) in children after cataract surgery during the first-year period and the risk of developing late-onset glaucoma. Children were included with the following criteria: they were≤10 years old and scheduled to undergo cataract surgery with/without intraocular lens implantation; they were compliant with our follow-up protocol, which included monitoring IOP using a Tono-Pen under sedation or anesthesia. Incidence of OH, peak OH value, OH onset time and OH duration within a 12-month period following surgery were measured. In brief, 206 patients (379 eyes) were included and OH developed in 66 of 379 (17.4%) eyes. The mean follow-up period was 14.0±3.2 months (median, 12 months; range, 10–16 months). Moreover, 33 of 196 (16.8%) aphakic eyes and 33 of 183 (18.0%) IOL eyes were diagnosed with OH. The peak OH onset times were at 1-week (34/66, 51.5%) and 1-month (14/66, 21.2%) appointments postsurgery. The peak IOP value in the OH eyes was 29.9±7.5 mmHg (median, 29 mmHg; range, 21–48 mmHg). The duration of OH was 30.9±31.2 days (median, 30 days; range, 3–150 days). OH recurred in 13 eyes with a history of OH diagnosed within 1 month postsurgery (13/54, 24.1%), which needed temporary or long term use of antiglaucoma medications. In conclusion, the incidence of OH in children after cataract surgery was 17.4% during the first-year period. Children who have suffered elevated IOP in the first year after cataract surgery should be followed closely to determine if there is an increased risk of developing late-onset glaucoma.     

Superovulatory response, embryo quality and fertility after treatment with different gonadotrophins in native cattle

We studied native Mertolengo cattle to evaluate superovulatory (SOV) treatments, subsequent fertility of donors and pregnancy rate of recovered embryos. In Experiment 1 we compared superovulatory response (SR), embryo quality and plasma progesterone (P4) levels between donors treated with eCG (10 cows and 5 heifers) vs. FSH (pure, FSH-1, n=10 cows and crude, FSH-2, n=10 cows), during progestagenic impregnation. We also compared fertilization rates and embryo quality of bred and inseminated eCG and FSH-1 donors. Significantly more viable embryos were yielded by FSH than by eCG treated donors. Less FSH-1 than FSH-2-treated donors showed SR, but the response was identical in responder donors of both groups. Fertilization rates were significantly higher in bred than in inseminated donors. Plasma P4 levels were only significantly different (higher) between responder and non-responder donors on the day of embryo recovery. Experiment 2 compared FSH treatments (FSH-2, crude, n=11 cows and FSH-3, pure, n=10 cows) started at the midluteal phase. The mean number of viable embryos was significantly higher in FSH-3 than in FSH-2 treated donors. Both FSH treatments exerted a similar luteotrophic effect upon injection. The FSH-2 donors treated during the midluteal phase yielded more ova and showed significantly higher plasma P4 levels at all sampling days than those treated during progestagenic impregnation. The pregnancy rates of recipient cows were 67% and 46% for fresh and frozen-thawed embryos respectively. In Experiment 3, the fertility of donors (n=20) after SOV treatments was compared with that of untreated cows (n=40). Time to conception of donors, after mating with a bull 14 days after embryo recovery, was identical to that of control cows. There was some delay to conception in eCG-treated cows, but the difference was not significant. These preliminary results suggest that response to SOV treatments in Mertolengo cattle might be affected by the type of gonadotrophin and by the treatment protocol. The fertility of a traditional breeding season after SOV treatments was not impaired. Cryopreserved embryo banking can be used to preserve the breed.