The global burden of congenital heart disease

Abstract

Although the incidence of congenital heart disease (CHD) is similar worldwide, the burden of supporting these patients falls more heavily on countries with high fertility rates. In a country with a fertility rate of about eight per woman, the population has to support four times as many children with CHD as in a country with a fertility rate of two. Countries with the highest fertility rates tend to have the lowest incomes per capita, thus accentuating the disparity. Countries with high fertility rates have more children with congenital heart disease per wage earner. Improving local health services and controlling infectious diseases (diarrhoeal illness, rheumatic fever, measles, rotoviral infection) are important but are mere ‘band-aids’ compared to improving education, empowering women and reducing birth rates.     

Glucose metabolic phenotype of pancreatic cancer

AIM: To construct a global "metabolic phenotype" of pancreatic ductal adenocarcinoma(PDAC) reflecting tumour-related metabolic enzyme expression.METHODS: A systematic review of the literature was performed using Ovid SP and Pub Med databases using keywords "pancreatic cancer" and individual glycolytic and mitochondrial oxidative phosphorylation(MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes.     

NSAID对胰腺癌中COX-2的表达及其生长活力的影响

目的 :检测胰腺癌中COX 2表达 ,探讨COX 2抑制剂非甾体类消炎药 (NSAID)的抑癌机制。方法 :胰腺癌组织和细胞株中的COX 2检测分别采用免疫组化和细胞免疫化学分析 ,并使用MTT法及流式细胞仪检测细胞株生长活力和凋亡。结果 :胰腺癌组织中COX 2的表达增强 ,阳性率 73.3% (P <0 .0 5 )。SW 1 990和Capan 2细胞株均有COX 2表达 ,前者高表达 ,后者低表达。两种NSAID(NS398及ASA)均可抑制两种细胞株的生长 ,诱导细胞凋亡率显著升高 ,并与细胞株COX 2表达强度有关 ;对SW 1 990细胞株的作用强于Capan 2 ,NS398的抑制作用又强于ASA。结论 :COX 2在胰腺癌组织和细胞株中表达增强 ,NSAID抗胰腺癌机制可能是通过抑制COX 2活性 ,诱导胰腺癌细胞凋亡     

实验性高胆固醇血症兔离体主动脉功能变化的研究

目的探讨高胆固醇血症对血管功能的影响。方法20只新西兰雄性兔随机分为2组正常饮食组(normal cholesterol,NC)10只及高胆固醇饮食组(hypercholesterol,HC)10只。4周后取出每只兔的降主动脉,5mm宽动脉环放置于含有25mlKreb液的组织－器官水浴系统中。分别测量游离血管对乙酰胆碱（10-10～10-5mol/L)的舒张反应及对去甲肾上腺素（10-10～10-5mol/L）的收缩反应。结果2组兔血胆固醇有显著差异,其中NC组（30.1±11.2）mg/dl,HC组（987.3±110.0)mg/dl(P<0.01);HC组血管对乙酰胆碱舒张反应与NC组比较明显减弱,HC组最大为（58.50±6.17）％,NC组最大为(103.2±6.9)％(P<0.01）;HC组血管对去甲肾上腺素反应增强,最大收缩力HC组为(4.15±0.56)g,NC组为(2.9±0.3)g(P<0.05）。2组动脉病理学检查无动脉硬化的改变。结论高胆固醇血症降低血管内皮依赖性舒张反应,增加血管对去甲肾上腺素的收缩反应。高胆固醇血症时血管内皮功能改变早于动脉粥样硬化的结构改变。     

2型糖尿病患者血浆同型半胱氨酸水平与冠心病的关系

目的探讨2型糖尿病患者血浆同型半胱氨酸（homocysteine,Hcy）水平与冠心病是否相关。方法回顾性分析169例2型糖尿病并已行选择性冠脉造影的患者,按冠脉狭窄程度分为对照组,单支组,双支组和多支病变组,分析不同组别Hcy及其他临床生化指标。结果冠心病各亚组Hcy均高于对照组（P〈0.05）,Hcy随冠脉病变程度的加重而升高,多支病变组Hcy明显高于单支组,与之呈正相关（P〈0.05）;多元逐步回归分析显示血浆同型半胱氨酸与冠脉狭窄程度明显相关（P〈0.05）。结论2型糖尿病患者血浆同型半胱氨酸水平升高有可能加重冠脉粥样硬化。     

URINARY BILE ACID CONJUGATES IN EXTRAHEPATIC BILIARY ATRESIA

The urinary excretion of bile acid conjugates was studied after the administration of 24-¹⁴C-labelled chenodeoxycholic acid and cholic acid and their corresponding glycine conjugates labelled with glycine-l-¹⁴T in 5 infants with extrahepatic biliary atresia. Chenodeoxycholic acid-24-¹⁴C and chenodeoxycholyl[l-¹⁴C]glycine were mainly excreted in the form of labelled metabolites with the TLC behaviour of monosulphates of tauro- and glycochenodeoxycholate and glycochenodeoxycholate, respectively. Most of the cholic acid-24-¹⁴C and the cholyl[l-¹⁴C]glycine were found to be excreted in the form of glycocholate. All labelled bile acids were excreted in conjugated form.     

AIDS-RELATED BEHAVIOUR IN ADOLESCENTS: INTERVENTION PROGRAMME WITH INTERNATIONAL APPLICATION

SUMMARY Adolescents and young adults comprise one of the fastest-growing categories of AIDS cases. The results of an opinion survey taken of 3242 adolescents raise serious doubts about the prevalent view that high-risk behaviour is attributable to insufficient information and education on AIDS: female adolescents are found to be at risk despite having the proper knowledge. Five chief factors affected the knowledge and behaviour of adolescents: age, gender, origin, family profession, and parental education. Each of the subpopulations (females, younger adolescents, children in rural areas) has its own characteristics and needs. We describe a permanent and long-term intervention programme, which might be applied in any country.     

Extracellular matrix components in Kimmelstiel Wilson nodules

Summary: The distribution of collagen types I, III, IV, V, VI, fibronectin laminin, tenascin, heparan sulfate proteoglycan and chondroitin sulphate proteoglycan was examined by light microscopy immunocytochemistry (ICC) in paraffin-embedded renal biopsies with nodular diabetic glomeruloscierosis. Immunoglobulin A, G and M, complement (C3c and C1q), fibrinogen and k and γ light chain deposition was also sought by ICC in the same tissue.
Kimmelstiel Wilson (KW) nodules were graded as either evolving (>3 nuclei present +/ - fibrillary appearance) or as late stage (amorphous and acellular). the extracellular matrix (ECM) components present in the evolving KW nodules were the same as those present in normal mesangial matrix but with an increased density. Late stage nodules displayed negative binding for all antibodies in their core with accentuated expression of the normal mesangial matrix components together with complement and 1gM at their periphery. Occasionally, when ruptures in Bowman's capsule (BC) were detected and adhesions between the capsule and the nodular tuft occurred, the interstitial collagens I and III were detected within laminations of Bowman's capsule, in Bowman's space, at adhesion sites and within some nodules.
The results suggest nodular lesions are initially formed by aggregation and/or increase in the normal components of mesangial matrix. the normal mesangial matrix constituent proteins are subsequently relocated to the periphery by amorphous material in which these ECM components are not detected. When BC is disrupted, interstitial collagens I and III may appear in Bowman's space and within nodules.     

Effect of saturable binding on the pharmacokinetics of drugs: a simulation

The time-courses of both total and unbound drug concentrations with time were simulated under conditions of saturable binding to either plasma proteins or tissues, or both, following a single intravenous dose. The curves were either linear, convex, or concave, depending upon the extent of distribution and the intrinsic ability of an eliminating organ to remove drug from the body. Saturable binding should therefore be considered whenever data showing nonlinear semilogarithmic decline are to be interpreted.