正常新生儿脐血血流变学的研究

本文总结报道了我院于1992-1993年对35例正常新生儿脐血进行血液流变学检测,结果提示正常新生儿早期全血粘度、血浆粘度、血小板聚集率,均较正常成人对照组显著增高;而红细胞沉降率显著降低.证明新生儿血液里高粘滞状态,这是新生儿疾病如新生儿硬肿症、肺出血、DIC等的病理生理基础,也为这些新生儿疾病的诊断和治疗提供了理论依据.     

Relationship between Mean Platelet Volume and Critical Limb Ischemia in Diabetes Mellitus Patients

The prevalence of diabetes mellitus continues to increase from year to year. Critical limb ischemia (CLI) is one of the complications of diabetes mellitus with a high mortality rate and requires amputation if not treated properly. Mean platelet volume (MPV) is an indicator of platelet activation and is expected to be a predictor of CLI in diabetes mellitus patients.This article investigates the relationship between MPV and the incidence of CLI in diabetes mellitus patients.This case–control study was conducted using the vascular registry of Dr. Sardjito Hospital, Yogyakarta, Indonesia, from January 2016 to December 2016. The relationship between MPV and the incidence of CLI was analyzed using bivariate and multivariate analysis. There was a significant association between MPV and incidence of CLI in diabetes mellitus patient both on bivariate analysis ( p  = 0.035) and multivariate analysis ( p  = 0.029). Diabetes mellitus patients with MPV values of ≥ 9.8 fl had a protective effect to prevent the incidence of CLI (bivariate analysis: odds ratio [OR] = 0.366, 95% confidence interval [CI] = 0.142–0.943; multivariate analysis: adjusted OR = 0.288, 95% CI = 0.09–0.88). Confounding factors such as sex, age, obesity, and use of antiplatelet agents were not associated with the incidence of CLI ( p  > 0.05). Meanwhile, history of dyslipidemia as a confounding factor was significantly associated with the incidence of CLI ( p  < 0.05). Low MPV was found to be significantly associated with the incidence of CLI in diabetes mellitus patients.     

免疫功能正常少年患早期表现为复视的隐球菌脑膜炎1例

目的:报告免疫力正常少年的隐球菌脑膜炎1例,早期表现为复视和双眼视力低下。方法:病例报告。结果:男,17岁,两眼视物模糊并复视3wk,伴随严重的搏动性头痛、恶心、呕吐及低热。经体格检查无发热及假性脑膜炎迹象。双眼视力为6/15并视野缩窄。双眼前段正常。眼外肌运动表明双侧第六神经麻痹。眼底检查显示双侧视盘充血和轻度隆起。CT扫描大脑正常,无颅内肿块或脑室异常。腰椎穿刺发现高开放压>300mmH2O。脑脊液显微镜下及培养均存在新型隐球菌。本例由神经医疗组联合处理。患者开始静脉注射两性霉素B和氟康唑,神经症状1wk后恢复,双眼视力提高到6/6,同时周边视野恢复。随着第六神经麻痹的康复双眼复视得到好转。结论:本例强调了隐球菌脑膜炎进展缓慢的性质。即使免疫功能正常,也不会存在明显的假性脑膜炎特征,复视可能是脑膜炎患者的早期表现之一。     

两性霉素B角膜基质内注射成功治疗真菌性角膜炎1例

目的:报告1例使用5mg/L两性霉素成功治疗难治性真菌性角膜炎的病例。方法:病例报告。结果:女性患者1例,48岁,以右眼红1wk,伴视力下降和角膜混浊2d入院。否认有外伤或异物史。检查发现:右眼视力:6/12,针孔视力:6/18。注射结膜前使眼分泌物保持最少。角膜旁中央区有一全层基质脓肿-形态不规则且伴有卫星病灶及羽状边缘,不伴有上皮缺损,有前房积脓液平。左眼正常。诊断为真菌性角膜炎。尽管在此前患者经历了3wk的局部两性霉素B点眼(1次/2h),那他霉素眼液点眼(1次/4h),但并无病情恢复的迹象。相反12点出现了一个新的更大的基质脓肿病灶。我们应用5mg/L两性霉素B角膜基质注射联合穿透性角膜移植术治疗后溃疡面积明显减少,前房积脓完全消失,没有毒性反应发生。患者干预后2mo视力恢复了正常视力(6/6)。结论:使用两性霉素B5mg/L基质内注射,使用过程安全有效,是一种治疗难治性真菌性角膜炎的理想方法。     

Effects of extended-release dipyridamole in vitro on thrombin indices measured by calibrated automated thrombography in poststroke survivors

Randomized trials suggested superior stroke prevention with extended-release dipyridamole (ERD) in combination with low-dose aspirin than either with aspirin or dipyridamole alone. Thrombin generation (TG) is a critical step in clot formation and represents a cornerstone biomarker of atherothrombosis. We, therefore, sought to define the effect of ERD in escalating concentrations on the time course of TG using the Calibrated Automated Thrombogram (CAT) technology in patients after ischemic stroke. Serial plasma samples were obtained from 20 patients with ischemic stroke documented by neuroimaging and who were treated with aspirin for at least 30 days. The impact of 75-, 150-, 250-, and 300-nM ERD on TG was assessed using fluorogenic substrate CAT technology. The following integrated CAT indices were calculated for each ERD dose and compared with the vehicle: TGmax, start time (tstart) peak time (tpeak), and mean time (tmean). Preincubation of platelet-poor plasma with ERD resulted in a dose-dependent significant inhibition of TG. The TGmax was gradually reduced from 447 ± 21 nM at baseline to 354 ± 31 nM (P = 0.008) for 75-nM ERD, 298 ± 24 nM for 150-nM ERD, 248 ± 26 nM for 250-nM ERD, and finally to 240 ± 23 nM for 300-nM ERD (P < 0.0001 for all). The tmean was reduced only for the highest (250-300 nM) ERD concentrations. The tstart was only slightly delayed, but not different (1.5 vs. 1.8 vs.1.9 minutes; P = 0.09), for all ERD concentrations. The tpeak was not affected by ERD. ERD in vitro affects thrombin activity indices predominantly by a dose-dependent inhibition of endogenous thrombin potential and demonstrated a trend to delayed initiation of thrombin production. These preliminary data, while intriguing, require confirmation in poststroke patients receiving orally dosed ERD to determine whether these findings are clinically relevant.     

In vitro anti-biofilm activity of macelignan isolated from Myristica fragrans Houtt. against oral primary colonizer bacteria

In early dental plaque formation, oral primary colonizers such as Streptococcus mutans, Streptococcus sanguis and Actinomyces viscosus are initially attached to the pellicle-coated tooth surface to form a biofilm. The study aimed to determine the efficacy of macelignan, isolated from nutmeg (Myristica fragrans Houtt.), in removing each single oral primary biofilm in vitro on a polystyrene 96-well microtiter plate. Four biofilm growth phases (4, 12, 20 and 24 h) were evaluated in this study after treatment with macelignan at various concentrations (0.2, 2 and 10 microg/mL) and exposure times (5, 10 and 30 min). Anti-biofilm activity of macelignan was measured as the percentage of the remaining biofilm absorbance after macelignan treatment in comparison with the untreated control. At 24 h of biofilm growth, S. mutans, A. viscosus and S. sanguis biofilms were reduced by up to 30%, 30% and 38%, respectively, after treatment with 10 microg/mL macelignan for 5 min. Increasing the treatment time to 30 min resulted in a reduction of more than 50% of each of the single primary biofilms. The results indicate that macelignan is a potent natural anti-biofilm agent against oral primary colonizers.     

Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies

The utility of anthracycline antineoplastic agents in the clinic is compromised by the risk of cardiotoxicity. It has been calculated that approximately 10% of patients treated with doxorubicin or its derivatives will develop cardiac complications up to 10 years after the cessation of chemotherapy. Oxidative stress has been established as the primary cause of cardiotoxicity. However, interventions reducing oxidative stress have not been successful at reducing the incidence of cardiotoxicity in patients treated with doxorubicin. New insights into the cardiomyocyte response to oxidative stress demonstrate that underlying differences between in vitro and in vivo toxicities may modulate the response to superoxide radicals and related compounds. This has led to potentially new uses for pre-existing drugs and new avenues of exploration to find better pharmacotherapies and interventions for the prevention of cardiotoxicity. However, much work still must be done to validate the clinical utility of these new approaches and proposed mechanisms. In this review, the authors have reviewed the molecular mechanisms of the pathogenesis of acute and chronic doxorubicin-induced cardiotoxicity and propose potential pharmacological interventions and treatment options to prevent or reverse this specific type of heart failure.     

Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice

Aims/hypothesis

Obesity is associated with ageing and increased energy intake, while restriction of energy intake improves health and longevity in multiple organisms; the NAD⁺-dependent deacetylase sirtuin 1 (SIRT1) is implicated in this process. Pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the arcuate nucleus (ARC) of the hypothalamus are critical for energy balance regulation, and the level of SIRT1 protein decreases with age in the ARC. In the current study we tested whether conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevents age-associated weight gain and diet-induced obesity.

Methods

We targeted Sirt1 cDNA sequence into the Rosa26 locus and generated conditional Sirt1 knock-in mice. These mice were crossed with mice harbouring either Pomc-Cre or Agrp-Cre and the metabolic variables, food intake, energy expenditure and sympathetic activity in adipose tissue of the resultant mice were analysed. We also used a hypothalamic cell line to investigate the molecular mechanism by which Sirt1 overexpression modulates leptin signalling.

Results

Conditional Sirt1 overexpression in mouse POMC or AgRP neurons prevented age-associated weight gain; overexpression in POMC neurons stimulated energy expenditure via increased sympathetic activity in adipose tissue, whereas overexpression in AgRP neurons suppressed food intake. SIRT1 improved leptin sensitivity in hypothalamic neurons in vitro and in vivo by downregulating protein-tyrosine phosphatase 1B, T cell protein-tyrosine phosphatase and suppressor of cytokine signalling 3. However, these phenotypes were absent in mice consuming a high-fat, high-sucrose diet due to decreases in ARC SIRT1 protein and hypothalamic NAD⁺ levels.

Conclusions/interpretation

ARC SIRT1 is a negative regulator of energy balance, and decline in ARC SIRT1 function contributes to disruption of energy homeostasis by ageing and diet-induced obesity.