Influence of the Mediterranean diet on carotid intima–media thickness in hypercholesterolaemic children: A 12-month intervention study

Background and aimsThe Mediterranean diet has been recognised as having a protective role on the cardiovascular system due to its low lipid and high antioxidant content. Lipid profile and oxidant status represent two important risk factors related to endothelial dysfunction, even at early stages of cardiovascular diseases. The aim of the study was to evaluate the influence of a 12-month Mediterranean diet on the variation of lipid profile and carotid intima–media thickness (cIMT) in pre-pubertal hypercholesterolaemic children.Methods and resultsWe performed a cross-sectional study comparing lipid profile and cIMT in a group of 68 pre-pubertal children (36 with hypercholesterolaemia and 32 controls). In addition, in the hypercholesterolaemic children a 12-month intervention programme with a Mediterranean diet was started to evaluate the variation of lipid profile and cIMT. At baseline, hypercholesterolaemic children showed a significantly higher cIMT (both right and left carotid artery) compared to controls (both p < 0.05). After 12 months of diet intervention, a significant reduction of total cholesterol, LDL-cholesterol and cIMT was documented (all p < 0.05). Furthermore, at the end of follow-up, delta body mass index-Standard Deviation score and delta LDL-cholesterol were significantly and independently related to the changes of cIMT (both p < 0.05).ConclusionThe Mediterranean diet represents a valid approach in the treatment of hypercholesterolaemia even during childhood.     

Inflammatory status modulates plasma lipid and inflammatory marker responses to kiwifruit consumption in hypercholesterolaemic men

Background and aimsKiwifruit has the potential to improve markers of metabolic dysfunction, but the response may be influenced by inflammatory state. We aimed to investigate whether inflammatory state would modulate the effect of consuming two green kiwifruit daily on plasma lipids and markers of inflammation.Methods and resultsEighty-five hypercholesterolaemic men completed a 4-week healthy diet run-in, before randomisation to a controlled cross-over study of two 4-week interventions of two green kiwifruit/day plus healthy diet (intervention) or healthy diet alone (control). Anthropometric measures and fasting blood samples (plasma lipids, serum apolipoproteins A1 and B, high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, tumour necrosis factor-alpha (TNF-α) and IL-10) were taken at baseline, 4 and 8 weeks. Subjects were divided into low and medium inflammatory groups, using pre-intervention hs-CRP concentrations (hs-CRP <1 and 1–3 mg/L, respectively).In the medium inflammatory group the kiwifruit intervention resulted in significant improvements in plasma high-density lipoprotein cholesterol (HDL-C) (mean difference 0.08 [95% CI: 0.03, 0.12] mmol/L [P < 0.001]), total cholesterol (TC)/HDL-C ratio (−0.29 [−0.45, −0.14] mmol/L [P = 0.001]), plasma hs-CRP (−22.1 [−33.6, −4.97]% [P = 0.01]) and IL-6 (−43.7 [−63.0, −14.1]% [P = 0.01]) compared to control treatment. No effects were seen in the low inflammatory group. There were significant between inflammation group differences for TC/HDL-C (P = 0.02), triglyceride (TG)/HDL-C (P = 0.05), and plasma IL-6 (P = 0.04).ConclusionsInflammatory state modulated responses to the kiwifruit intervention by improving inflammatory markers and lipid profiles in subjects with modestly elevated CRP, suggesting this group may particularly benefit from the regular consumption of green kiwifruit.Registered 16th March 2010, Australian New Zealand Clinical Trials Registry (no. ACTRN12610000213044), www.ANZCTR.org.au.     

Indices de sécurité d’une recanalisation antérograde d’occlusion coronaire chronique sans injection controlatérale en première intention. À propos d’une série consécutive de 39 cas

IntroductionCurrent guidelines for chronic total occlusion (CTO) percutaneous coronary intervention (PCI) recommend dual coronary angiography.Aim of the studyEvaluate CTO-PCI with a single approach using safety indices through the microcatheter.Population and methodsProspective observational study with a consecutive inclusion of 39 patients (mean age of 67 years) treated by antegrade approach without scheduled contralateral angiography. Following safety indices were collected: blood backflow, distal coronary pressure waveform, selective distal contrast injection.ResultsTechnical success was obtained in 90% of the cases. Balloon dilation was used in 38% of the cases before placement of the microcatheter. Dual angiography was necessary in three cases (8%). A blood backflow and cyclic changes of the distal coronary pressure waveform were noticed in 87% and 84% of the cases, with a positive predictive value of 97% and 79% respectively, for a microcatheter location in the true lumen. Selective distal contrast injection was done in 36 cases with a visualization of the true lumen in 35 cases. One major complication was observed (3%).ConclusionCTO-PCI with a single approach is feasible using safety indices to limit the risks of major complication. The principle of a systematic dual angiography as advocated in current guidelines may deserve to be revisited.     

胰腺癌诊治指南(2014)

<正>1前言2014年最新统计数据显示,发达国家(美国)胰腺癌新发估计病例数,男性列第10位,女性列第9位,占恶性肿瘤病死率的第4位。据《2013年中国肿瘤登记年报》统计,胰腺癌位列我国男性恶性肿瘤发病率的第8位,人群恶性肿瘤病死率的第7位,全球范围内均呈快速上升趋势。我国地域辽阔,各地经济及医疗水平差距较大,为了进一步规范胰腺癌的诊断与治疗,提高多学科综合诊治水平,中华     

Time Interval of Two Injections and First-Dose Dependent of Accelerated Blood Clearance Phenomenon Induced by PEGylated Liposomal Gambogenic Acid: The Contribution of PEG-Specific IgM

Repeated injection of PEGylated liposomes can cause the disappearance of long circulating property because of the induction of anti-PEG IgM antibody referred to as “accelerated blood clearance (ABC) phenomenon.” Although ABC phenomenon typically occurs when entrapped drugs are chemotherapeutic agent with low cytotoxic, there is little evidence of accelerated blood clearance of PEGylated herbal-derived compound on repeated injection. Herein, we investigated the blood concentration of PEGylated liposomal gambogenic acid (PEG-GEA-L), a model PEGylated liposomal herbal extract, on its repeated injection to rats. We found time interval between injections had considerable impact on the magnitude of ABC phenomenon induced by PEG-GEA-L. When time interval was prolonged from 3 days to 7 days, ABC phenomenon could be attenuated. Furthermore, its magnitude was enhanced accompanied by a marked rise in the accumulation of PEG-GEA-L in the liver and spleen in a first-dose–dependent manner. Consistently, the level of anti-PEG IgM significantly increased with the first dose of PEG-GEA-L and decreased with the extended time interval between injections, which implies anti-PEG IgM is a major contributor to the ABC phenomenon. Notably, the increased expression of liver anti-PEG IgM was accompanied by an increased expression of efflux transporters in the induction process of the ABC phenomenon.     

The Hypotonic Environmental Changes Affect Liposomal Formulations for Nose-to-Brain Targeted Drug Delivery

Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within minutes. However, the nasal mucosa properties (e.g., tonicity, pH) are not constant because of physiological and environmental factors, and this might limit the therapeutic outcome of nanocarrier-based formulations. To shine light on the impact of environmental ionic strength on nanocarrier-based formulations, we have studied how liposomal formulations respond to the change of tonicity of the external environment. Large unilamellar vesicles loaded with 6 different drugs were exposed to different hypotonic environments, creating an osmotic gradient within the inner core and external environment of the liposomes up to 650 mOsm/kg. Both size and polydispersity of liposomes were significantly affected by tonicity changes. Moreover, the release kinetics of hydrophilic and lipophilic drugs were largely enhanced by hypotonic environments. These results clearly demonstrate that the environmental ionic strength has an impact on liposomal formulation stability and drug release kinetics and it should be considered when liposomal formulations for nose-to-brain targeted drug delivery are designed.     

鬼针草总黄酮通过ERK1/2/NF-κB通路减轻局灶性脑缺血大鼠认知功能障碍

摘要：目的 探讨鬼针草总黄酮（TFB）对局灶性脑缺血大鼠认知功能的影响及可能的作用机制。方法 72只大 鼠随机分为假手术组、模型组、阳性对照组（1 mg/kg尼莫地平）、低剂量TFB组（25 mg/kg）、中剂量TFB组（50 mg/kg）、 高剂量TFB组（100 mg/kg）,每组12只。采用改良线栓法建立局灶性脑缺血大鼠模型。Morris水迷宫实验检测大鼠 学习和记忆能力,尼氏染色观察大鼠海马组织病理结构变化,酶联免疫吸附法检测海马组织脑源性神经营养因子 （BDNF）、神经生长因子（NGF）、白介素-1β（IL-1β）、白介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）含量,Western blot 检测海马组织细胞外信号调节蛋白激酶（ERK）1/2、p-ERK1/2、核转录因子（NF）-κB p65和p-NF-κB p65蛋白表达。 结果 与假手术组比,模型组大鼠逃避潜伏期延长,穿越平台次数减少,海马组织BDNF和NGF含量均降低,IL-1β、 IL-6和TNF-α含量以及p-ERK1/2和p-NF-κB p65蛋白表达水平均升高（P＜0.05）。与模型组比,第2天之后高剂量 TFB组和阳性对照组大鼠平均逃避潜伏期均降低（P＜0.05）,中、高剂量TFB组和阳性对照组大鼠穿越平台次数增 加,海马组织BDNF和NGF含量升高（P＜0.05）,IL-1β、IL-6和TNF-α含量以及p-ERK1/2和p-NF-κB p65蛋白表达 水平均降低,具有剂量依赖性（P＜0.05）。阳性对照组和高剂量TFB组大鼠各检测指标比较差异无统计学意义（P＞ 0.05）。结论 TFB可改善局灶性脑缺血大鼠的认知功能,其作用机制可能与抑制ERK1/2/NF-κB信号通路的传导 有关。     

Reconstruction of the temporomandibular joint: a comparison between prefabricated and customized alloplastic prosthetic total joint systems

The implantation of an alloplastic total temporomandibular joint (TMJ) prosthesis is an innovative approach for the treatment of end-stage TMJ disorders. Two types of system exist: prefabricated (stock) and customized computer-aided design/computer-aided manufacturing (CAD/CAM) devices. A clinical study was performed to evaluate the effectiveness of these two designs. Twenty-eight patients treated between 2015 and 2017 were included and assigned to two groups: stock prostheses (group 1) and customized CAD/CAM prostheses (group 2). Clinical evaluations were performed at five time-points up to 6 months postoperative. Parameters included maximum interincisal opening, pain, diet, complications, and subjective well-being at the end of follow-up. Differences between pre-surgery and 6-month post-surgery values were highly significant (P < 0.001). No patient required a liquid diet at the end of treatment, and 66% of group 1 patients and 100% of group 2 patients reported improved well-being. Complications were observed in 32% of patients and included temporary paralysis of the facial nerve. In conclusion, clinical outcomes of stock and CAD/CAM prostheses suggested great improvements in mouth opening and reduction of pain as a result of the rehabilitation of TMJ function. Results showed comparable data for the two types of prosthesis design at 6 months postoperative.