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.     

Moxonidine improves glycaemic control in mildly hypertensive, overweight patients: a comparison with metformin

AIM: To compare the effects of moxonidine and metformin on glycaemic control in patients with impaired glucose tolerance and signs of the metabolic syndrome. METHODS: A multicentre, prospective, randomized, open-label study design was adopted with blinded endpoint evaluation. Patients > or =40 years old, with impaired glucose tolerance (or diabetes mellitus treated with diet alone) and a body mass index (BMI) of at least 27 kg/m2 were treated twice daily with moxonidine 0.2 mg or metformin 500 mg for 16 weeks. Oral glucose tolerance test (OGTT) was performed at baseline and end-of-study; plasma insulin and plasma glucose levels were measured at 0, 60, 120 and 180 min after administration. RESULTS: With regard to effects on insulin [mean area under the curve (AUC) for insulin], the primary efficacy endpoint of the study, both drugs did not show equivalence. On the contrary, in the per protocol (PP) population, moxonidine statistically significantly (p = 0.025) decreased the AUC for insulin from baseline in the PP population; for metformin, the treatment effect on insulin was a small, net increase resulting in a statistically significant between-group difference of 16.2% (95% CI = 0.1-35.0). The change in mean insulin AUC was most marked in the subgroup of patients with higher sympathetic activity (heart rate >80 bpm). Mean fasting plasma glucose (FPG) levels and HbA1c levels were largely unchanged by moxonidine treatment but significantly decreased by metformin treatment. The difference between the groups was 14.7% (p = 0.0523) in the intent-to-treat (ITT) sample. By study end, both treatments had significantly increased the Matsuda Insulin Sensitivity Index (ISI) from baseline to a comparable extent: moxonidine by reducing plasma insulin after a glucose challenge, metformin by reducing FPG. BMI fell significantly in both groups and blood pressure normalized; both drugs were well tolerated. CONCLUSIONS: Moxonidine improved insulin sensitivity in response to glucose challenge in patients with evidence of metabolic syndrome. This improvement resulted from a reduction in plasma insulin levels and was most marked in patients with high sympathetic drive at baseline. By enhancing insulin sensitivity, moxonidine treatment may help prevent the development of diabetes and thereby ameliorate the risk for cardiovascular disease.     

Using nonselective endothelin receptor antagonist in idiopathic pulmonary hypertension

Idiopathic (primary) pulmonary hypertension (IPH) is a rare disease of unknown etiology, which is characterized by elevated pulmonary artery pressure, increased total pulmonary vascular resistance, frequently a malignant course with evolving right ventricular decompensation, and a fatal outcome. The diagnosis of IPH is established on the increments in the mean resting and exercise pulmonary artery trunk pressure by more than 25 and more than 30 mm Hg at rest and during exercise, respectively, with a normal pulmonary artery wedge pressure. Endothelin receptor antagonists (ERA) are one of the effective classes of drugs for the treatment of patients with IPH. Bosentan is the first drug from the ERA class that blocks the receptors of both types and that has been recommended by the WHO to treat patients with functional class II-IV pulmonary hypertension. The described case demonstrates the possibility of concomitantly using bosentan in a female patient with IPH shortly after ineffective treatment with a calcium antagonist.     

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.     

Diagnosis of myocardial infarct with fatal outcome within the framework of multifactorial prevention of ischemic heart disease in Moscow

The death diagnosis of myocardial infarction (including acute heart failure) was recorded and verified on the basis of standard criteria during a 5-year implementation of the Program on Multifactorial Prevention of Coronary Heart Disease among males aged 40-59 years. The analysis demonstrated that the hyperdiagnosis of acute heart failure as a death cause was observed in 29.0% of cases, death being due to acute alcohol intoxication in 43% of all the inconsistent diagnoses.     

Pseudohypoparathyroidism. Clinical characteristics and experience with its treatment with vitamin D 3 preparations

The paper is concerned with the literature data on pathogenesis and a clinical course of 2 types of PHPT. Clinicolaboratory findings show that PHPT is a polymorphous syndrome of which the most common signs are skeletal changes, low stature, the tetanoid syndrome in hypocalcemia, hyperphosphatemia, the normal or raised level of endogenous PTH, insensitivity to exogenous PTH, soft tissue and brain calcification, mental deficiency. An insufficient or paradoxical PTH reaction and an adequate CT reaction are noted after calcium drug loading. Therapy with I alpha OH D3 and I alpha, 25/OH2 D3 has demonstrated its superiority over other vitamin D forms leading to fast normalization of calcium-phosphoric metabolism and elimination of the tetanoid syndrome.