Gracilaria changii(Rhodophyta) alleviates bisphenol A-induced adverse reproductive abnormalities in mice

Objective: To evaluate the potential of Gracilaria changii extract in ameliorating the potential adverse effects of bisphenol A. Methods: The antioxidant capacity of Gracilaria changii extracted using different solvents(methanol, ethanol, and aqueous) was studied. The mice were administered by oral gavage with bisphenol A(60 mg/kg body weight) for 6 weeks with or without Gracilaria changii aqueous extract. Thereafter, the mice were either euthanized for histology and immunohistochemistry studies or mated to evaluate the pregnancy rate. Results: Gracilaria changii aqueous extract showed the highest antioxidant properties compared with extract using methanol and ethanol. The aqueous extract of Gracilaria changii improved the uterus index and uterine lipid peroxidation after bisphenol A exposure, although the uterine expressions of estrogen receptors and complement C3 were not improved. Histological evaluation of the uterus during the estrus stage has revealed that the extract could mitigate bisphenol A-induced adverse effects in the uterus as there was a lower percentage of mice showing abnormalities like decreased eosin staining in the myometrium, and decrease in the number of eosinophil and endometrial glands in the endometrium. Besides, Gracilaria changii aqueous extract improved the pregnancy rate of mice administered with bisphenol A. Conclusions: Gracilaria changii extract protects against bisphenol A-induced female reproductive abnormalities in mice which may be mediated via modulation of eosinophil migration, endometrial gland formation, and protein expressions associated with prostaglandins in the myometrium.     

Exploring the reasons for low pertussis vaccine effectiveness in Ontario,Canada, 2006–2008: a Canadian Immunization Research Network study

ObjectivesAlthough pertussis vaccines have been widely used for many decades, a burden of illness persists. Resurgences in Ontario, Canada, have not been substantial in the past decade, but an outbreak of pertussis occurred in Toronto between 1 October 2005 and 31 March 2006. Previous Ontario studies found high vaccine effectiveness (VE) in the initial years post-immunization. In order to explore the impact of outbreaks and external factors on VE, we investigated pertussis VE during the period 2006–2008.MethodsWe assessed pertussis VE using a frequency-matched case-control study for the period 1 March 2006 to 31 December 2008. We used logistic regression to estimate VE by age, time since last vaccination, and vaccination status according to the Ontario recommended schedule. We compared analyses including and excluding cases from Toronto, and to two recent Ontario pertussis VE studies.ResultsWe included 1797 confirmed cases and 7188 matched controls. Most cases were under 4 years of age during the study period. Pertussis VE was 3.8% (95% CI: − 21.0, 24.0) in the period 15–364 days following the last pertussis vaccine dose, and increased with increasing time since vaccination. Pertussis VE in the first 15–364 days excluding Toronto increased to 57.1% (95% CI: 26.0, 75.1), but the trend of increasing VE with time since vaccination persisted. Although VE was higher in older (6–11 years) than younger (0–5 years) children, it was lower at 12–13 years than after 14 years.ConclusionVE was lower in comparison with other studies conducted in Ontario, particularly in younger children. Various factors occurring during the study period may have influenced the results, including clinical testing of asymptomatic contacts, laboratory testing and methods and reporting practice, and a sensitive case definition. Further studies are needed to optimize methods for measuring VE to inform pertussis vaccine policy.     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

Ultrafiltration for acute decompensated heart failure: A systematic review and meta-analysis of randomized controlled trials

Background

Current clinical guidelines recommend ultrafiltration (UF) for patients with acute decompensated heart failure (ADHF) who are unresponsive or resistant to diuretics. We systematically reviewed the latest randomized evidence on the efficacy and safety of UF in ADHF.

Methods

MEDLINE, EMBASE and the Cochrane database were searched in January 2013 for eligible randomized controlled trials (RCTs) evaluating UF in patients with ADHF. A Mantel–Haenszel random-effects model was used to calculate mean differences (MDs) and odds ratios (ORs) for continuous and dichotomous data, respectively, with 95% confidence intervals (CIs).

Results

Data of 12 studies (n = 659) were meta-analyzed; follow-up duration ranged from 36 h to 12 months. Compared to control, treatment of UF was associated with significant fluid removal (MD 1.28, 95% CI 0.43 to 2.12, P = 0.003) and weight loss (MD 1.23, 95% CI 0.03 to 2.44, P = 0.04), with no significant effects on all-cause mortality (OR 1.08, 95% CI 0.63 to 1.86, P = 0.77) or all-cause rehospitalization (OR 0.89, 95% CI 0.39 to 2.00, P = 0.77). No significant differences were observed in the analyses of change in serum creatinine or unscheduled medical care; analysis of adverse effects was inconclusive since only one study provided usable data.

Conclusions

For patients with ADHF, UF is effective in reducing fluid retention and body weight, with no significant benefits in mortality or rehospitalization. The current limited randomized evidence highlights the need for further well-conducted randomized studies of adequate power to establish the role of UF in ADHF patients for whom conventional HF treatment is unsuccessful or contraindicated.     

A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium

Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the « molar tooth sign ». JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice‐site mutation in PDE6D, encoding a prenyl‐binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild‐type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl‐dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP‐bound ARL3, which acts as a cargo‐release factor for PDE6D‐bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl‐binding‐dependent trafficking in ciliopathies.     

四种中成药对气血双虚模型小鼠血象及免疫水平的影响

目的:为艾滋病抗病毒疗法所致的骨髓不良反应筛选疗效确切的中成药,观察分析参芪颗粒、复方阿胶浆、贞芪扶正颗粒、复方皂矾丸四种中成药对放血和注射环磷酰胺联合复制的气血双虚模型小鼠血象及免疫水平的影响。方法:实验于2005-08/09在河南中医学院药理实验室完成。①参芪颗粒(江西山高制药有限公司生产,批号040702);复方阿胶浆(山东东阿阿胶股份有限公司生产,批号050446);贞芪扶正颗粒(甘肃扶正药业科技股份有限公司生产,批号040803);复方皂矾丸(陕西郝其军制药有限责任公司生产,批号041014);当归补血口服液(郑州市协和制药厂生产,批号041122);环磷酰胺(上海华联制药有限公司生产,批号050101)。②选取清洁级昆明种小鼠150只,随机数字表法分为15组,10只/组:1～3组分别灌服参芪颗粒混悬液3,2,1g/kg;4～6组分别灌服复方阿胶浆30,20,10mL/kg;7～9组分别灌服贞芪扶正颗粒混悬液15,10,5g/kg;10～12组分别灌服复方皂矾丸混悬液2.4,1.6,0.8g/kg;第13组灌服当归补血口服液10g/kg;剩余2组为空白对照组和模型对照组,分别给于同体积生理盐水10g/kg。各组给药1次/d,连续给药10d。③除空白对照组外,其他各组从给药第1天开始建立气血双虚模型。每只鼠尾部放血0.25mL/10g,然后分别于第2,4,6,8天腹腔注射环磷酰胺80,40,40,40mg/kg。空白对照组同时间点仅腹腔注射等体积生理盐水。末次注射环磷酰胺后2h,眼眶取血,一部分用于血象测定,另一部分离心取血清,测定血细胞比容及血清中巨噬细胞集落刺激因子水平;解剖取胸腺和脾脏,检测胸腺皮质厚度、胸腺淋巴细胞数、脾小结大小、脾脏淋巴细胞数病理学指标的变化。结果:150只小鼠全部进入结果分析,放血和注射环磷酰胺并用可成功建立小鼠气血双虚模型。①与模型对照组比较,参芪颗粒3g/kg组、贞芪扶正颗粒10,5g/kg组、复方皂矾丸1.6g/kg组均可升高气血双虚模型小鼠白细胞水平(t=2.18～2.74,P<0.05),贞芪扶正颗粒15g/kg组作用更为显著(t=2.98,P<0.01);参芪颗粒1g/kg组、复方阿胶浆20mL/kg组、贞芪扶正颗粒15,10g/kg组均可升高红细胞水平(t=2.44～2.69,P<0.05),复方阿胶浆30mL/kg组、贞芪扶正颗粒5g/kg组、复方皂矾丸2.4,1.6g/kg组作用更为显著(t=2.91～3.66,P<0.01);当归补血口服液组、复方阿胶浆20mL/kg组、参芪颗粒3,1g/kg组、贞芪扶正颗粒15,10,5g/kg组均可升高血红蛋白水平(t=2.27～2.85,P<0.05),复方阿胶浆30mL/kg组、复方皂矾丸2.4,1.6g/kg组作用更为显著(t=3.07～4.04,P<0.01);当归补血口服液组、参芪颗粒3,2g/kg组均可升高血小板水平(t=2.20～2.41,P<0.05)。②与模型对照组比较,参芪颗粒2g/kg组、贞芪扶正颗粒5g/kg组均可升高气血双虚模型小鼠血细胞比容(t=2.01～2.62,P<0.05),参芪颗粒1g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6,0.8g/kg组作用更为显著(t=3.18～4.36,P<0.01);参芪颗粒2g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6g/kg组均可显著升高巨噬细胞集落刺激因子水平(t=3.60～6.80,P<0.01)。③与模型对照组比较,当归补血口服液组、参芪颗粒3,2,1g/kg组、复方阿胶浆30,20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4,1.6,0.8g/kg组均可显著增加气血双虚模型小鼠胸腺皮质厚度(t=3.71～9.34,P<0.01),增大脾小结(t=3.36～11.97,P<0.01),增加脾脏淋巴细胞数(t=4.29～10.44,P<0.01);复方阿胶浆30mL/kg组可明显增加小鼠胸腺淋巴细胞数(t=2.45,P<0.05),当归补血口服液组、参芪颗粒3,2,1g/kg组、复方阿胶浆20,10mL/kg组、贞芪扶正颗粒15,10,5g/kg组、复方皂矾丸2.4g/kg组作用更为显著(t=3.22～8.20,P<0.01)。结论:①四种中成药对气血双虚模型小鼠血红蛋白升高作用相近,以复方阿胶浆和贞芪扶正颗粒对白细胞和红细胞水平升高作用为强,以复方阿胶浆和贞芪扶正颗粒对血小板水平升高作用为优。②四种中成药对气血双虚模型小鼠血细胞比容的影响无差异,以贞芪扶正颗粒和复方皂矾丸对巨噬细胞集落刺激因子水平的升高作用为优。③以参芪颗粒、复方阿胶浆、贞芪扶正颗粒对胸腺皮质厚度和淋巴细胞数的促进作用为优,以参芪颗粒、贞芪扶正颗粒、复方皂矾丸对脾小结和脾脏淋巴细胞数的促进作用为优。     

含抗生素骨水泥假体在人工关节术后感染中的应用

目的 回顾分析含抗生素骨水泥假体(PROSTALAC)治疗人工关节置换术后感染的疗效。方法 对16例髋和膝关节置换术后感染的病例采用PROSTALAC方法，进行二期翻修治疗并进行随访。结果 16例髋和膝关节置换术后感染中，有14例于治疗后接受二期全髋或全膝关节翻修术，经平均46月的随访，感染无复发，成功率达87．5％。术后Harris髋关节评分平均达82．9分，膝关节评分平均达90．5分。结论 在PROSTALAC基础上进行的二期全髋和全膝关节翻修手术能成功地治疗人工关节术后感染，并且保持术后关节的功能。     

Outcome analysis of 40 cases of vestibular schwannoma: A comparison of sitting and Park bench surgical position

The present study retrospectively reviews our experience in 40 cases of vestibular schwannoma, operated between the years 1995 and 2002. All the patients underwent tumour resection either in sitting or in the Park bench position via the suboccipital retromastoid route. The position of the patient was selected arbitrarily. Precordial Doppler echocardiography was used to monitor air embolism. Operative results, including the size of the tumour, completeness of resection, anatomical and functional preservation of the facial nerve, operative complications and mortality were analysed and compared in these two operative positions. There was no statistically significant difference in terms of surgical results between these two groups.      

Lipomatous meningioma: Diagnostic pitfalls and pathological updates

We present a case of histologically confirmed lipomatous meningioma, the first to our knowledge reported in Hong Kong. A 75‐year‐old woman presented to us with on and off dizziness for 1 month. Computed tomography (CT) of the brain showed an extra‐axial mass lesion containing fat and solid enhancing foci at her right frontal region. The definitive diagnosis could be made preoperatively. Postoperative histological examination of the tumour revealed the diagnosis of lipomatous meningioma. We have reviewed the literature and discussed the diagnostic clues, clinical presentation and pathology of this rare tumour.