Increased levels of tissue plasminogen activator with a low plasminogen activator inhibitor-1 in a patient with postoperative bleeding

Recurrent postoperative bleeding in a previously healthy man with a moderate prolongation of PT and PTT which did not correct with vigorous fresh-frozen plasma infusion was identified as a unique abnormality of the fibrinolytic system: a combination of an excess of tissue plasminogen activator (t-PA) at 300% of normal activity accompanied by a concurrent deficiency of plasminogen activator inhibitor-1 activity (PAI-1) of 10-20% of normal activity. This observation underscores the potentially important regulatory role of PAI-1 in the degree to which clinical manifestations of bleeding tendencies may occur in patients in whom an excess amount of t-PA is expressed.     

冠心病伴高血脂症患者的纤溶功能改变及血脂康的影响

目的:研究冠心病并高血脂症患者纤溶、纤溶储备功能的改变及血脂康的影响。方法:40例冠心病人[其中12例总胆固醇(TC)升高;10例甘油三酯(TG)升高;18例TG、TC均升高],于入院第1天采集静脉血测定纤溶指标后服用血脂康(0.6mg,每日2次);于4周后再次行纤溶指标检查,同时做静脉闭塞实验以确定最大内皮组织纤溶酶原激活物(t-PA)水平并与10例正常者对比。结果:经4周血脂康治疗后,t-PA活性、t-PA/PA I比值明显升高(P<0.01)纤溶储备功能明显改善(P<0.05)。结论:血脂康能明显改善冠心病高脂血症患者的纤溶储备功能。     

体外治疗性超声对大鼠纤溶系统的影响

目的　研究体外治疗性超声对大鼠血浆组织型纤溶酶原激活因子 (t-PA)、纤溶酶原激活物抑制因子 -1(PAI -1)的影响。方法　采用酶联免疫吸附法测定超声治疗前后大鼠血浆t-PA、PAI -1的改变。结果　超声治疗后ETUS组t-PA(0 .5 4± 0 .19)IU/ml,PAI -1(0 .44± 0 .18)AU/ml,对照组t -PA(0 .5 1± 0 .2 5 )IU/ml,PAI -1(0 .43± 0 .19)AU/ml,二者比较无明显差异 (P >0 .0 5 )。结论　治疗剂量超声对大鼠纤溶系统没有影响     

GnRH类似物治疗对男性前列腺癌患者骨丢失的影响

目的探讨GnRH类似物治疗对老年男性前列腺癌患者骨量丢失、骨转换及身体成分的影响。方法确诊前列腺癌患者33人,同年龄健康男性35人,分别在治疗前、治疗12个月后测定受试者腰椎24（L2-4）、左股骨颈（FN）、全髋（Total Hip）的骨密度及全身总骨量、体脂（Total fat mass）和肌肉（Total lean mass）含量,并检测血清骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、250HD、尿Ⅰ型胶原C端交联物（CTX）等骨转换指标。结果前列腺癌GnRH类似物治疗组和对照组相比基线水平的骨密度和骨代谢各项指标间都没有显著性差异,GnRH类似物治疗12个月后,血FSH、T、E2分别下降了66．0％、87．5％和75．0％（P〈0．01）,血PSA水平下降100％（P〈0．001）;腰椎、股骨颈、全髋及全身骨量丢失率分别为-2．05％、-3．55％、-3．47％和-3．64％,与对照组相比各部位骨量的下降均有显著性差异（P〈0．05）;Total fat mass和Total lean mass变化率分别为＋12．6％和-10．8％,与对照组相比lean mass下降具有显著性差异（P〈0．05）;尿CTX／Cr和血250HD变化率分别为＋54．71％和-43．75％,与对照组相比变化率有显著性差异（P〈0．05）。6个月时骨转换标记物尿CTX／Cr的变化率与12个月时骨丢失率呈负相关。结论前列腺癌患者接受GnRH类似物治疗后出现明显的骨转换加速、骨量丢失增加及身体脂肪肌肉成分的改变,对这些病人及时监测骨密度和骨转换指标有利于早期诊断早期防治。     

辛伐他汀对冠心病患者纤溶参数的影响

目的了解冠心病患者纤溶参数的变化,并观察辛伐他汀对冠心病患者纤溶参数的影响。方法测定87例正常对照者和108例冠心病患者血浆组织型纤溶酶原激活物(t-PA)活性和纤溶酶原激活物抑制物-(1PAI-1)活性,随后108例冠心病患者被随机分成常规治疗组和常规治疗+辛伐他汀40mg每日一次(辛伐他汀组)。治疗14d后复测t-PA活性和PAI-1活性。结果与正常对照组相比较,冠心病患者纤溶参数异常,t-PA活性下降,PAI-1活性上升(P<0.01)。常规治疗组治疗后纤溶参数无显著变化(P>0.05)。辛伐他汀组纤溶参数明显改善,表现为t-PA活性上升,PAI-1活性下降(P<0.01)。结论冠心病患者纤溶参数明显异常,辛伐他汀能改善冠心病患者纤溶参数。     

Effect of the angiotensin II receptor blocker candesartan on fibrinolysis in patients with mild hypertension

Aim:  Impaired fibrinolysis is frequently observed in patients with the metabolic syndrome. Aim of the study was to examine the short-term effect of angiotensin II receptor blockade on the fibrinolytic system.
Methods:  Seventy-four patients with mild hypertension were randomly assigned to a 7-day treatment period with either 16 mg candesartan cilexetil or placebo. Several variables of the fibrinolytic system such as plasminogen activator inhibitor-1 (PAI-1) antigen and activity, tissue plasminogen activator (t-PA) antigen and activity as well as circulating t-PA/PAI-1 complexes were determined.
Results:  At baseline, the body mass index but not blood pressure was positively associated with PAI-1 antigen (r = 0.314, p < 0.01) and PAI-1 activity (r = 0.425, p < 0.01) but negatively with t-PA activity (r = −0.187, p < 0.05). A 7-day treatment with 16 mg candesartan cilexetil resulted in a significant greater reduction of diastolic blood pressure (−10.3 ± 10.8 mmHg vs.−5.8 ± 8.5 mmHg, p = 0.03). However, there was no significant effect of candesartan on all parameters of the fibrinolytic system under investigation, i.e. circulating PAI-1 antigen, PAI-1 activity, t-PA antigen, t-PA activity and t-PA/PAI-1 complexes. Furthermore, candesartan did not affect the characteristic circadian pattern of the variables of the fibrinolytic system.
Conclusion:  We conclude that short-term blockade of the angiotensin II receptor subtype 1 with candesartan does not have an impact on fibrinolysis in patients with mild hypertension.     

The effects of TNF alpha inhibition on plasma fibrinolytic balance in patients with chronic inflammatory rheumatical disorders

OBJECTIVE: Recent studies support an inflammatory basis for atherosclerosis. Patients with chronic inflammatory rheumatical disorders are at increased risk for cardiovascular events, and this can be partially attributed to the inhibition of fibrinolytic system. TNF a inhibitors such as infliximab are shown to retard the progression of inflammatory arthritides. In this study, we investigated the effects of infliximab on plasma fibrinolytic parameters. METHODS: Thirteen patients (7 female, 6 male; mean age: 44 +/- 11 years) with a clinical indication for infliximab (rheumatoid arthritis (RA) (n = 8), ankylosing spondylitis (AS) (n = 5)) were selected. Plasma plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA) antigens (Ag) and high sensitive C-reactive protein (hs-CRP) levels were measured during low salt intake at baseline. All patients received infliximab (Remicaide, i.v. infusion, 3 mg/kg). Plasma PAI-1 Ag, t-PA Ag and hs-CRP were measured during low salt intake at the end of 2 weeks. All samples were collected at 9 AM. Antigen levels were determined using a 2-site enzyme-linked immunosorbent assay. RESULTS: Patients experienced significant improvement in disease related activity scores after infliximab treatment. DAS score (for rheumatoid arthritis) and BASDAI index (for ankylosing spondylitis) decreased significantly after treatment (p = 0.01 and p = 0.04 respectively). Infliximab significantly reduced the marker of inflammation (hs-CRP) (8.3 +/- 3.9 vs. 4 +/- 4.1 mg/L, p < 0.01). Plasma PAI-1 antigen (64.7 +/- 26.9 vs. 40 +/- 31.1 ng/ml, p = 0.03) and PAI-1/t-PA ratio (10.8 +/- 5.9 vs. 6.6 +/- 3.8, p = 0.02) were significantly lower after the treatment. In contrast, plasma t-PA levels were unchanged (9.4 +/- 4.4 vs. 9.0 +/- 4.3 ng/ml, p = 0.73). CONCLUSION: This study provides evidence that TNF alpha inhibition with infliximab decreases PAI-1 Ag level and PAI-1/t-PA ratio, and hence activates fibrinolytic system in patients with chronic inflammatory disorders.     

Long-term effects of GLP-1 receptor agonists in type 2 diabetic patients: A retrospective real-life study in 131 patients

AimWe evaluate retrospectively long-term effects of GLP-1 receptor agonists in type 2 diabetic patients treated between 2008 and 2016.Methods131 patients treated by GLP-1 receptor agonists (GLP-1RAs) were included. The objective was to evaluate the evolution of glycated hemoglobin (HbA_1c) during a period up to 4 years. The secondary objectives consisted of analysing the long-term effects of treatment on body mass index (BMI), blood pressure and lipids; reporting the proportion of patients who reached HbA_1c objectives; estimating the time before treatment failure and determining predictive factors of failure. We also compared twice-daily exenatide to once-daily liraglutide on the major parameters.ResultsHbA_1c improved significantly, mostly during the first year of treatment (−1.2%), and this effect was maintained after 4 years (−1.4% vs. baseline). At 1 year, 26% and 47% of subjects achieved HbA_1c levels <7.0% and 7.5%, respectively. Treatment failure was observed in 51% of patients after a mean duration of GLP-1RA treatment of 50 months. Half of patients had failed after 42 months. Baseline HbA_1c greater than 9.0% and male gender were predictive factors of treatment failure. BMI also decreased: −0.9 kg/m² the first year, −1.9 kg/m² after 4 years. No significant difference was found between patients treated with exenatide and liragutide over time.ConclusionsThe beneficial effects of GLP-1RAs on HbA_1c reached a plateau after the first year of treatment and are maintained at 4 years only in one third of patients. Failure occurred predominantly in men with a baseline HbA_1c greater than 9%.     

Mucociliary clearance in patients with chronic asthma: effects of beta agonists

OBJECTIVE: Chronic asthma is characterized by airway inflammation, mucus hypersecretion and impaired mucociliary clearance (MCC). We investigated baseline MCC and the acute effect of terbutaline in chronic asthmatics with sputum production while on long-term treatment with salmeterol in combination with inhaled corticosteroids (ICS). METHODOLOGY: MCC was measured at baseline and in response to 1 mg terbutaline (or placebo) on three visits over 80 min in 16 asthmatics (52+/-13 years of age). Subjects who had greater than 10% absolute increase in MCC above baseline and placebo, after terbutaline, were categorized in group A and subjects who had less than 10% in group B. RESULTs: In group A subjects (n=6), MCC increased from 23.7+/-4.0% at baseline to 43.7+/-4.9% with terbutaline (P<0.0001) and to 34.4+/-5.7% with placebo (P<0.01). In group B subjects (n=10), MCC remained similar: 11.3+/-3.2% at initial baseline, 12.0+/-3.2% with terbutaline and 7.3+/-3.0% with placebo (P>0.05). Group B subjects withdrew from all beta(2) agonists for a week and MCC was remeasured. After withdrawal, baseline MCC (7.0+/-1.8%) was similar to the initial baseline value (P>0.1) and MCC with terbutaline (15.8+/-4.9%) was greater than baseline (P<0.005) but remained abnormal in most subjects. Baseline percentage predicted FEV(1) and FEF(25--75%) were 77.3+/-7.2 and 41.7+/-5.6 in group A and 59.9+/-8.1 and 29.5+/-8.4 in group B subjects, respectively. CONCLUSION: MCC was impaired in most of these asthmatics with persistent airway obstruction and sputum production, despite regular treatment with ICS and salmeterol. In addition, there was little or no stimulation of MCC acutely after terbutaline in most of these asthmatics.     

Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer

Background Degradation of the extracellular matrix plays an important part during the invasion of cancer cells into the surrounding tissue. The matrix metalloproteinases (MMPs) have a central role in this process as demonstrated in different malignancies. The aim of this study was to investigate the presence of several MMPs from tumour, adjacent tumour-free colon segment and from plasma, in order to evaluate how these factors might be used as predictors in colorectal malignancy.Methods Seventy-two patients who underwent surgery because of a colorectal carcinoma were included. Biopsies from the tumour, macroscopically tumour-free bowel and plasma samples were analysed with enzyme-linked immunosorbent assay tests (ELISAs) quantifying protein expression of several MMPs.Results We found highly elevated concentrations of MMP-1, MMP-2, MMP-3 and MMP-9 protein expression in tumour tissue compared with tumour-free tissue (p<0.0001). Elevated MMP-1 tumour levels were found in patients with Dukes C cancers (p=0.02). Lymph node status correlated with the expression of MMP-2 in plasma, which was significantly increased in patients with lymph node metastasis compared with those without (p=0.002). MMP-2 in plasma was higher in T3 and T2 tumours than in T4 tumours (p=0.0083).Conclusion The MMPs we investigated were strongly elevated in tumour tissue compared with tumour-free bowel wall. Our results indicate that MMP-2 in plasma may possibly be used as a predictor in colorectal malignancy. The use of MMP-2 as a predicting tool in combination with different imaging techniques may give important preoperative information in patients with colorectal cancer.     

Effects of glucagon-like peptide-1 receptor agonists on major coronary events in patients with type 2 diabetes

Aims

To perform a meta-analysis to assess the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on major coronary events, including myocardial infarction (MI), unstable angina and coronary revascularization, in patients with type 2 diabetes mellitus (T2DM).

Materials and methods

We systematically searched the PubMed, CENTRAL, EMBASE and clinicaltrial.gov databases to seek eligible studies with a cardiovascular endpoint comparing GLP-1RAs with a placebo in T2DM patients. Odds ratio (ORs) and 95% confidence intervals (CIs) were calculated for the outcomes.

Results

Nine studies, with a total of 64 236 patients, were included. GLP-1RA treatment reduced fatal and nonfatal MI by 8% (OR 0.92, 95% CI 0.86–0.99; P = 0.02, I² = 39%). The reduction reached 15% in human-based GLP-1RA-treated patients. Similarly, once-weekly GLP-1RA treatment reduced the risk of MI by 13%. In contrast, GLP-1RA treatment did not reduce the risk of hospitalization for unstable angina (OR 1.11, 95% CI 0.97–1.28; P = 0.13, I² = 21%). GLP-1RAs exhibited a tendency to lower the risk of coronary revascularization (OR 0.95, 95% CI 0.89–1.02; P = 0.15, I² = 22%), but without statistical significance. Human-based GLP-1RAs decreased the risk by 11%.

Conclusions

In high-risk patients with T2DM, GLP-1RAs were associated with a decrease in MI, especially the human-based and once-weekly GLP-1RAs. No benefit was seen for hospitalization for unstable angina or coronary revascularization. Further research is urgently needed to ascertain improvements in coronary events.     

早期血浆置换治疗重症高脂血症性胰腺炎患者的临床疗效

目的观察早期血浆置换对重症高脂血症性胰腺炎的治疗效果。方法选取临床确诊的36例重症高脂血症性胰腺炎患者,随机分为两组:对照组20例采用内科传统治疗;治疗组16例在内科传统治疗的基础上给予早期单次床旁血浆置换治疗。比较两组血常规、血清淀粉酶、血糖、甘油三酯、C-反应蛋白(CRP)、降钙素原(PCT)、白细胞介素-6(IL-6)、可溶性细胞间黏附分子-1(sICAM-1)等指标的变化。结果经治疗后两组血常规、血淀粉酶、血糖、甘油三酯、CRP、PCT、IL-6和sICAM-1等指标均有不同程度的改善,其中治疗组改善尤为明显,较治疗前和对照组治疗后差异有统计学意义(P均0.05)。结论早期行血浆置治疗急性高脂血症性重症胰腺炎能有效减轻炎症反应,阻止病情发展。     

紫杉醇联合顺铂治疗晚期乳腺癌26例的近期疗效

目的评价紫杉醇联合顺铂对晚期乳腺癌的治疗作用。方法采用紫杉醇联合顺铂的联合方案，治疗晚期乳腺癌26例，初治患者10例，余16例均行根治术以后行辅助性放化疗后复发和（或）转移的患者，其中有2例在复发转移后曾用过ADM、CTX、5-FU联合化疗。均经细胞学或病理证实。结果本组完全缓解（CR）2例（7．69％），部分缓解（PR）13例（50．00％），有效率（CR＋PR）57．69％。主要毒性为骨髓抑制及消化道反应。结论紫杉醇联合顺铂方案是治疗晚期乳腺癌较为理想的方案。     

The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens in patients with advanced prostate cancer

The effect of flutamide on basal and ACTH-stimulated plasma levels of adrenal androgens was investigated in 6 patients with untreated advanced prostate cancer, aged 52-75 yr. Flutamide was administered (250 mg three times daily) for 10 days; before and after treatment, a synthetic ACTH1-24 stimulation test (250 micrograms im, with blood sampling immediately before and 60 min after the stimulus) was performed. Basal plasma 17OH-pregnenolone (delta 5-17OHP), 170H-progesterone (delta 4-17OHP), androstenedione (A), dehydroepiandrosterone (DHEA) and its sulphate (DHEAS) were unchanged by flutamide treatment. In contrast, basal plasma testosterone (T) concentrations significantly increased (p less than 0.05). The response of cortisol delta 4-17OHP, delta 5-17OHP, A and DHEA to ACTH, as well as the ACTH-stimulated delta 5-17OHP/delta 4-17OHP, delta 5-17OHP/DHEA, delta 4-17OHP/A and DHEA/A ratios, were unchanged by flutamide treatment. These findings indicate that: a) Short-term flutamide administration enhances testicular steroidogenesis, via augmented LH pulse frequency; b) Adrenal steroidogenesis seems to be not affected by the drug, since ACTH-stimulated plasma levels of adrenal androgens and precursors/products ratios were unchanged.     

Short term effects of infliximab on the lipid profile in patients with rheumatoid arthritis

OBJECTIVE: Cardiovascular morbidity and mortality appear to be enhanced in rheumatoid arthritis (RA), which might be due to an increased prevalence of cardiovascular risk factors such as dyslipidemia. It was recently shown that effective disease modifying antirheumatic drug treatment had a favorable influence on the lipid profile in patients with active RA. As infliximab markedly reduces disease activity in RA, we investigated the effects of infliximab on the lipid profile. METHODS: Infliximab was administered at baseline and at 2 and 6 weeks in patients with active RA. Total cholesterol and HDL-cholesterol concentrations were measured and their ratio, the atherogenic index (an important cardiovascular risk factor indicator), was assessed. RESULTS: Sixty-nine patients were enrolled. The Disease Activity Index score (DAS-28) was 5.9 (SD +/- 1.4) at baseline and decreased to 4.6 (+/- 1.4) after 2 weeks and further to 4.1 (+/- 1.5) after 6 weeks. Total cholesterol level was 5.2 mmol/l at baseline and increased to 5.7 mmol/l (p < 0.001) at 2 weeks, and was 5.6 mmol/l (p < 0.001 vs baseline) at Week 6. For HDL-cholesterol these values were 1.5, 1.6 (p < 0.001), and 1.6 mmol/l (p < 0.001 vs baseline), respectively. Changes in disease activity were significantly inversely associated with changes in total cholesterol and HDL-cholesterol levels. The atherogenic index, however, remained constant. Corticosteroid use at baseline was associated with significantly higher total cholesterol and HDL-cholesterol levels and a lower (more favorable) atherogenic index at baseline. CONCLUSION: Infliximab treatment was associated with a significant increase of both total cholesterol and HDL-cholesterol levels, which correlated with decreasing disease activity. However, this was not accompanied by a favorable effect on the atherogenic index. The favorable effect of infliximab on cardiovascular comorbidity might not be mediated by effects on lipid metabolism, but longterm investigations are needed to confirm this.     

改良坐站训练对卒中后偏瘫平衡功能的改善作用

目的探讨改良坐站训练对卒中后偏瘫患者平衡功能的影响。方法首发单侧脑卒中患者16例,随机分为常规组和改良组。2组治疗方法差异在于改良组在坐站训练中增加了屈膝位的蹲踞动作控制点。采用Berg平衡功能量表和动态步态指数评定患者平衡功能。结果常规组在治疗后有部分平衡项目改善,而改良组所有项目均有显著改善,且在由坐位到站位、由站位到坐位、双足并拢站立不需扶持、手臂前伸、转身360°等项目比常规组显著改善。结论在传统坐站训练中增加屈膝位控制训练有助于改良坐站训练效果,改善患者平衡功能。     

Antioxidant enzyme activities and lipid peroxides in the plasma of patients with benign prostatic hyperplasia or prostate cancer are not predictive

In this study, lipid peroxide and total sulfhydryl contents and activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were investigated in the plasma of patients with benign prostatic hyperplasia (BPH) and prostate cancer. No significant change was found in lipid peroxidation or antioxidant systems in the plasma of patients with BPH and prostate cancer. The results indicate that evaluation of the prooxidant-antioxidant balance in the plasma of BPH and prostate cancer patients cannot be used as a marker to discriminate between these diseases. Received: 5 November 1998 / Accepted: 19 January 1999     

The effect of sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide 1 agonists on cardiovascular disease in patients with type 2 diabetes

Patients with type 2 diabetes have a significantly increased risk of cardiovascular disease (CVD) compared to the general population—with CVD accounting for two out of every three deaths in patients with diabetes. In 2008, the FDA suggested that CVD risk should be evaluated for any new antidiabetic therapy, leading to a multitude of large CVD outcome trials to assess CVD risk from these medications. Interestingly, several of these outcome trials with new novel antidiabetic therapies have demonstrated a clear and definite CVD advantage at mid‐term follow up in high‐risk patients with T2DM. In this review, we discuss two relatively new classes of diabetic drugs, sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide 1 agonists, and their efficacy in improving cardiovascular outcomes.     

重型肝炎患者血浆对体外培养猪肝细胞的影响

有研究证实肝衰竭患者血浆或血清对体外培养的HepG2、HHY41细胞有毒性作用。现阶段生物人工肝临床研究的主要细胞材料为猪肝细胞，肝衰竭患者血浆对其毒性作用研究鲜见报道，因此研究旨在采用猪肝细胞，观察我国数量众多的慢性乙型病毒性重型肝炎患者血浆对其体外影响。