Direct stenting with 3000 i.u. heparin

In order to reduce vascular complications, the authors assessed safety and feasability of a new percutaneous transluminal coronary angioplasty (PTCA) strategy consisting of direct stenting with 3000 i.u. heparin and immediate sheath removal. Predicting factors of vascular complications during PTCA include heparin dosages, sheath dwell time and use of anti-glycoprotein (GP) IIb/IIIa. A simplified PTCA with direct stenting technique may allow the use of very low doses of heparin without anti-GPIIb/IIIa in selected cases. From April 1999 to April 2000 all patients who underwent PTCA in the authors' center were screened. Exclusion criteria comprised a contraindication for direct stenting, primary PTCA for acute myocardial infarction (MI) and a TIMI (thrombolysis in myocardial infarction) grade zero flow. All other patients were included. They received 3000 i.u. heparin before direct stenting whatever their current anticoagulation and their weight. The sheath was immediately removed using manual compression. Out of 716 consecutive PTCA patients, 171 (24%) were enrolled in the study (198 sites). Complete protocol was achieved in 150 patients (88%). Activated clotting time during the procedure was 179 +/- 32 seconds. No subacute thrombosis or creatine kinase elevation was observed before discharge. Only two uncomplicated groin hematomas and two false aneurysms (one surgical repair) were noted. This study shows that direct stenting with 3000 iu heparin is safe. Immediate sheath removal can be performed with a low rate of major vascular complications.     

The catalytically active secretory phospholipase A2 type IIA is involved in restenosis development after PTCA in human coronary arteries and generation of atherogenic LDL

Secretory phospholipase A₂ type IIA (sPLA₂) may actively contribute to atherogenesis, acting either within the arterial wall or in plasma. Proinflammatory eicosanoids and lysophospholipids, generated through hydrolysis of cell membrane phospholipids by sPLA₂, initiate and prolong the inflammatory process. In the present study we examined the possible involvement of sPLA₂ in development of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). We also investigated whether serum sPLA₂ could catalyze accumulation of lysophosphatidylcholine (LPC) in LDL. Concentrations and catalytic activities of sPLA₂ were measured in blood serum of 49 consenting patients immediately before, 1–7 and 180 days after PTCA. All patients had repeat angiograms at 180-day follow-up. Restenosis was registered in 19 patients. Accumulation of LPC in LDL was evaluated by thin-layer chromatography after incubation of blood serum with LDL. Serum sPLA₂ concentrations increased in all study patients by day 1 post-PTCA, but the increase was significantly greater and more protracted in patients who developed restenosis. Catalytic activities increased significantly 6 days post-PTCA in patients who developed restenosis, whereas for patients without restenosis there was no change in serum sPLA₂ activity throughout the study period in spite of the sPLA2 presence in blood. Incubation of blood serum (6 days post-PTCA) with LDL resulted in accumulation of LPC only for those patients who subsequently developed restenosis. Manoalide, a specific inhibitor of sPLA₂, completely blocked the LPC accumulation. The data indicate that elevated serum sPLA₂ activity after PTCA is associated with restenosis development and may be involved in atherogenic modification of LDL in blood serum. (Mol Cell Biochem 270: 107–113, 2005)     

The use of adjunctive GPIIb/IIIa inhibitors in patients with unstable angina/non-Q-wave MI undergoing percutaneous coronary intervention

Glycoprotein IIb/IIIa receptor inhibitors represent a relatively new therapeutic approach in the field of antiplatelet therapy. Following the development of abciximab a number of small molecule GPIIb/IIIa inhibitors have been introduced such as tirofiban and eptifibatide. In this fast-moving field the interventional cardiologist needs a framework to guide decision-making for the individual patient. This review covers the efficacy and safety data from the clinical trials of GPIIb/IIIa inhibitors in the context of patients undergoing percutaneous coronary intervention for unstable angina/non-Q-wave myocardial infarction. There is an increasing body of evidence to support the efficacy of GPIIb/IIIa inhibitors in reducing the risk of adverse ischemic events in high and low risk patients undergoing percutaneous coronary intervention. A number of unresolved efficacy and safety issues remain, including the duration of treatment before and after intervention; whether a reduction in the heparin dose would further decrease the risk of hemorrhage without affecting the periprocedural thrombotic rate in patients undergoing PTCA with adjunctive GPIIb/IIIa inhibitors; and the cost-effectiveness of this therapy. When a thorough analysis of cost-effectiveness has been made, it will be easier to advocate the widespread use of these agents in all patients undergoing coronary intervention.     

Minority status in an ethnic democracy: The status of the Arab minority in Israel

It is commonly assumed that democracy in deeply divided societies takes either a majoritarian or consociational form. While the state in both types is ethnically neutral, there are some countries that combine viable democratic institutions with institutionalized ethnic dominance. The article introduces this third, so far not recognized, general type of ‘ethnic democracy’ and demonstrates its utility for Israel in treating its Arab minority. The tensions and contradictions in Israel's dual character as a Jewish democratic state give rise to five Arab demands that the Jewish majority reject: making Israel non‐Jewish and non‐Zionist, accepting Palestinian nationalism, lifting all restrictions on Arab individual rights, granting Arabs certain national collective rights and incorporating Arabs into the national power structure. Each Arab demand is discussed in detail and the rationale for Jewish objections is spelled out. The problem can be reduced, but not resolved, by establishing a separate Palestinian state in the West Bank and Gaza Strip for the Palestinian people and by according Israeli Arabs the status of a Palestinian national minority within the Jewish state. These issues are not unique to Israel but rather common to ethnic democracies. It is concluded that the Israeli experience is becoming increasingly relevant to states which are democratizing but keeping appreciable ethnic dominance.     

Increased Expression of Phosphorylated Polo-Like Kinase 1 and Histone in Bypass Vein Graft and Coronary Arteries following Angioplasty

Interventional procedures, including percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass surgery (CABG) to re-vascularize occluded coronary arteries, injure the vascular wall and cause endothelial denudation and medial vascular smooth muscle cell (VSMCs) metaplasia. Proliferation of the phenotypically altered SMCs is the key event in the pathogenesis of intimal hyperplasia (IH). Several kinases and phosphatases regulate cell cycle in SMC proliferation. It is our hypothesis that increased expression and activity of polo-like kinase-1 (PLK1) in SMCs, following PTCA and CABG, contributes to greater SMC proliferation in the injured than uninjured blood vessels. Using immunofluorescence (IF), we assessed the expression of PLK1 and phosphorylated-PLK1 (pPLK1) in post-PTCA coronary arteries, and superficial epigastric vein grafts (SEV) and compared it with those in the corresponding uninjured vessels. We also compared the expressions of mitotic marker phospho-histone, synthetic-SMC marker, contractile SMC marker, IFN-γ and phosphorylated STAT-3 in the post-PTCA arteries, SEV-grafts, and the uninjured vessels. Immunostaining demonstrated an increase in the number of cells expressing PLK1 and pPLK1 in the neointima of post PTCA-coronary arteries and SEV-grafts compared to their uninjured counterparts. VSMCs in the neointima showed an increased expression of phospho-histone, synthetic and contractile SMC markers, IFN-γ and phosphorylated STAT-3. However, VSMCs of uninjured coronaries and SEV had no significant expression of the aforementioned proteins. These data suggest that PLK1 might play a critical role in VSMC mitosis in hyperplastic intima of the injured vessels. Thus, novel therapies to inhibit PLK1 could be developed to inhibit the mitogenesis of VSMCs and control neointimal hyperplasia.     

Aqueous lithium heparin is a superior anticoagulant to solid heparin for blood collection from the retro-orbital sinus of rats

Blood specimens from the retro-orbital sinus of 80 Sprague Dawley rats were collected into tubes containing lithium heparin either as a solid or an aqueous solution. Plasma was separated for blood chemistry analysis. Twenty-eight blood specimens collected into tubes containing solid heparin were clotted and eight specimens were partially clotted making these samples unsuitable for some analyses. None of the specimens collected into heparin solution showed any evidence of clotting. The variances of lactate dehydrogenase and alpha-hydroxybutyrate dehydrogenase activities in plasma prepared with solid heparin were significantly greater than those prepared with heparin solution. Lithium heparin solution is now used routinely in our laboratory.     

The effect of growth hormones on bananas: A review

An attempt has been made to compile the knowledge from the available literature. The growth regulators reviewed include auxins, gibberellins, cytokinins, ethephon, CCC, Alar, ABA, morphactin and TIBA. None of them is used routinely. The chlorophenoxy and naphthalene compounds are definitely harmful. All others discussed are worthy of further study.Contribution from the Agricultural Research Organization, The Volcani Center, Bet Dagan, Israel. No. 593-E, 1982 series.     

Monitoring Important Bird Areas in Africa: Towards a Sustainable and Scaleable System

The need for effective global monitoring of biodiversity is clearer than ever, but our measurements remain patchy and inadequate. In the biodiversity-rich tropics, a central problem is the sustainability of monitoring schemes. Locally-based, participatory approaches show promise in overcoming this problem, but may not contribute effectively to monitoring at larger scales. BirdLife International’s framework for monitoring Important Bird Areas (IBAs) in Africa is designed to be simple, robust and locally-grounded, but to produce scaleable results that can be compiled into national or regional indices. Focusing on key sites for bird conservation, identified according to standard criteria, the framework institutionalises monitoring in site management authorities and Site Support Groups (community-based organisations of local people working for conservation and sustainable development). A small, central monitoring unit co-ordinates the programme nationally, compiles, analyses and manages data, and provides feedback. ‘Basic’ monitoring (taking place at all sites) involves scoring of state, pressure and response trends using site information submitted on simple forms. ‘Detailed’ monitoring (taking place at a selected sub-set of sites) involves more intensive measurement of particular variables that relate to site management targets. IBA monitoring is now underway in at least 10 African countries, with implementation of the framework most advanced (thanks to a pilot project) in Kenya. The 2004 IBA monitoring report for Kenya provides extensive information on individual IBAs, plus indices for national trends in state, pressure and response, based on data from 49 out of 60 sites. The experience in Kenya shows that institutionalisation is vital, but takes considerable time and effort; that adequate co-ordination (including timely feedback) is key; and that participatory monitoring has many valuable benefits beyond the data collected. Further work is being undertaken to refine the process, improve its scientific underpinning, and strengthen the feedback loop from data and analysis to action on the ground.     

Inhibition of heparan sulphate and other glycosaminoglycans binding to Helicobacter pylori by various polysulphated carbohydrates

Abstract Heparan sulphate binding to Helicobacter pylori at pH 4 to 5 was inhibited with various sulphated polysaccharides (heparin and chondroitin sulphates, fucoidan, carrageenans and some others), but not by carboxylated or nonsulphated compounds. Heparin binding proteins are exposed on the cell surface.     

Heparin and antiheparin in childhood. 3. Heparin level measurements and their importance in heparin monitoring

Measurements of the heparin level were made under continuous anticoagulation in a total of 7 patients. For the purpose of monitoring heparin the coagulation time values were determined parallelly. Except a patient with a sepsis and a 7 days old newborn baby the desired prolongation for the partial thromboplastin time and the reaction time of thrombelastogram resulted from heparin titres lying within the range of 0.2-0.7 U/ml of plasma. Even after applying depot preparations there was a relatively good correspondance of heparin level curves and coagulation parameters. In childhood the partial thromboplastin time is primarily suitable for monitoring the heparin therapy. Heparin half-life times calculated during the transumbilical exchange transfusion in 7 children amounted to values ranging between 40-110 minutes. In addition to checking low dose heparinizing, measurements of the level are suitable for deriving dosage standards for neutralizing heparin effects by protamine sulfate.     

Heparin and other glycosaminoglycans stimulate the formation of amyloid fibrils from alpha-synuclein in vitro

Parkinson's disease is the second most common neurodegenerative disease and results from loss of dopaminergic neurons in the substantia nigra. The aggregation and fibrillation of alpha-synuclein have been implicated as a causative factor in the disease. Glycosaminoglycans (GAGs) are routinely found associated with amyloid deposits in most amyloidosis diseases, and there is evidence to support an active role of GAGs in amyloid fibril formation in some cases. In contrast to the extracellular amyloid deposits, the alpha-synuclein deposits in Lewy body diseases are intracellular, and thus it is less clear whether GAGs may be involved. To determine whether the presence of GAGs does affect the fibrillation of alpha-synuclein, the kinetics of fibril formation were investigated in the presence of a number of GAGs and other charged polymers. Certain GAGs (heparin, heparan sulfate) and other highly sulfated polymers (dextran sulfate) were found to significantly stimulate the formation of alpha-synuclein fibrils. Interestingly, the interaction of GAGs with alpha-synuclein is quite specific, since some GAGs, e.g., keratan sulfate, had negligible effect. Heparin not only increased the rate of fibrillation but also apparently increased the yield of fibrils. The molar ratio of heparin to alpha-synuclein and the incorporation of fluorescein-labeled heparin into the fibrils demonstrate that the heparin is integrated into the fibrils and is not just a catalyst for fibrillation. The apparent dissociation constant for heparin in stimulating alpha-synuclein fibrillation was 0.19 microM, indicating a strong affinity. Similar effects of heparin were observed with the A53T and A30P mutants of alpha-synuclein. Since there is some evidence that Lewy bodies may contain GAGs, these observations may be very relevant in the context of the etiology of Parkinson's disease.     

Safety and efficacy of treatment with platelet GPIIb/IIIa receptor blockade in unstable angina patients awaiting PTCA at a referring clinic

BACKGROUND: Although balloon angioplasty has assumed an important role in the management of refractory unstable angina (UA), that is, UA that does not respond to conventional therapy, it is limited by complications related to thrombosis and acute coronary occlusion. The complication rate is higher in patients with UA than in those whose condition is stable. Preprocedural use of abciximab, a monoclonal platelet glycoprotein IIb/IIIa receptor blocker, has been used effectively in patients with UA, but its acceptance may be limited by safety concerns and economic constraints. The current trial investigated a protocol for abciximab pretreatment in patients with UA awaiting transfer from referring hospitals to a site of intervention (the 'drip and ship' protocol). AIMS: This observational study was conducted to evaluate whether a prophylactic, preprocedural regimen of abciximab can be safely and effectively administered to UA patients in referring hospitals while awaiting coronary angioplasty at the interventional clinic. METHODS: From April 1996 to December 1998, 168 consecutive patients with refractory UA (Braunwald class II or III) received abciximab prospectively at the referring clinic before undergoing PTCA or stent implantation at the interventional clinic. The following cost-conscious protocol was used: a 0.25 mg/kg bolus of abciximab followed by 10 micro g/min intravenously for 16 hours, in addition to intravenous nitrates, heparin and aspirin therapy. Patients were then transferred to a facility with PTCA capability via high-speed ambulance transport. No specific alterations of routine-transfer protocol were needed. Platelet aggregation studies were conducted during abciximab infusion. All interventions were performed while abciximab was given. Procedural and clinical success and long-term outcomes also were assessed. RESULTS: The primary angiographic success rate (patients with post-PTCA diameter stenosis < 50%) was 98%, and the in-hospital clinical success rate (angiographic success without major complications) was 98%. No major bleeding complications occurred during the abciximab pretreatment period. Platelet aggregation findings in the study patients showed a stable inhibition of >80% at the time of angioplasty. At 30-day follow-up, all patients were alive and 91% were free of major adverse events. Outcomes of balloon angioplasty and stenting were equally favorable, indicating no device-specific effect. Event-free survival at six months was 89% with a target vessel revascularization rate of 10%. CONCLUSION: Abciximab was administered safely and effectively to angioplasty patients with refractory UA awaiting transfer from a noninterventional setting to the site of angioplasty. These results extend the current knowledge base that has been established in randomized trials performed in interventional centers. The study protocol potentially could make abciximab therapy more feasible economically, and therefore more widely available to patients who are most likely to benefit from prophylactic administration.     

Association between coronary lesion severity and distal microvascular resistance in patients with coronary artery disease

Homogeneity of microvascular resistance in different perfusion areas of the same heart is generally assumed. We investigated the effect of the severity of an epicardial stenosis on microvascular resistance in 27 patients with coronary artery disease and stable angina. All patients had an angiographically normal coronary artery, an artery with an intermediate lesion, and an artery with a severe lesion; the latter was treated with angioplasty. In each patient, distal blood flow velocity and pressure were measured during baseline and maximal hyperemia (induced by intracoronary adenosine) using a Doppler and pressure guide wire, respectively. The ratio of mean distal pressure to average peak blood flow velocity was used as an index for the microvascular resistance (MRv). Within patients, the hyperemic MRv was higher in arteries with more severe stenosis (P = 0.021). After percutaneous transluminal coronary angioplasty (PTCA), the hyperemic MRv decreased (pre-PTCA, 2.6 vs. post-PTCA, 1.9 mmHg.cm(-1)s(-1), P < 0.01) toward the value of the reference artery (1.7 mmHg.cm(-1)s(-1); P = 0.67). We conclude that there is a positive association between coronary lesion severity and variability of distal microvascular resistance that normalizes after angioplasty. This study challenges the concept of uniform distribution of hyperemic MRv that is relevant for the interpretation of both noninvasive and invasive diagnostic tests.     

Coupled oxygen transport analysis in the avascular wall of a coronary artery stenosis during angioplasty

The coupled oxygen transport in the avascular wall of a coronary artery stenosis is studied numerically by solving the convection-diffusion equations. Two geometries replicating stenosis before and after percutaneous transluminal coronary angioplasty (PTCA) are used for the analysis. The results are compared to evaluate the effect of the degree of stenosis on oxygen transport. Important physiological aspects, such as oxygen consumption in the wall, oxygen carried by the hemoglobin, non-Newtonian viscosity of the blood, and supply of oxygen from the vasa vasorum are included. The results show that the PO2 in the medial region of the arterial wall is approximately 10mmHg. The oxygen flux to the wall increases in the flow acceleration region, whereas it decreases at the flow reattachment zone. Near the location of flow separation, there is a small rise followed by a sharp fall in the oxygen flux. The drop in the oxygen flux to the wall at the point of flow reattachment for pre-PTCA stenosis is four times that for post-PTCA stenosis. The minimum PO2 in the avascular wall, PO2,min, at this location decreases to approximately 6.0 and 4.2mmHg for post- and pre-PTCA stenosis, respectively. The drop in PO2,w and PO2,min at the point of flow reattachment for pre-PTCA is approximately 2 times that for post-PTCA stenosis. Thus, the present study quantifies the oxygen transport to the arterial wall before and after cardiovascular intervention.     

In vitro effects of pregnancy-associated plasma protein-A: artifacts due to heparin

Pregnancy-associated plasma protein-A (PAPP-A) has been reported to inhibit elastase activity, lymphoblastogenesis, complement activity, and thrombin-induced coagulation of fibrinogen. Since some of these results are controversial, we reevaluate here the effects of PAPP-A in these last two systems. By molecular sieve chromatography, PAPP-A immunoreactivity and inhibitory activity on thrombin and complement were dissociated. A PAPP-A-free washing of the heparin-Sepharose column used during the purification of PAPP-A showed inhibitory activities similar to those of purified PAPP-A. Furthermore, a preparation of PAPP-A that had not been submitted to heparin-Sepharose chromatography during purification was not active in either assays. Thus, the anticoagulant and anti-complement effects previously attributed to PAPP-A were due to a contaminant of low molecular mass. We believe that this contaminant is probably heparin. A protocol to eliminate free and PAPP-A-bound heparin is presented herein, and implications for other previously reported in vitro effects of PAPP-A are discussed.     

Effect of egg yolk and seminal plasma heparin binding protein interaction on the freezability of buffalo cauda epididymal spermatozoa

Egg yolk is routinely used in most of the extenders for cryopreservation of semen, but mechanisms of protection of spermatozoa by egg yolk are not very clear. Investigations with buffalo cauda epididymal sperm have shown that seminal plasma heparin binding proteins have detrimental effects during semen cryopreservation. The present study was conducted to investigate the effect of egg yolk on the detrimental effects of heparin binding proteins during cryopreservation of buffalo cauda epididymal spermatozoa. The results indicated that egg yolk was able to reduce the heparin binding proteins mediated cryoinjury in spermatozoa. One of the mechanisms of protection of spermatozoa from cryoinjury by egg yolk may be due to the inhibition of deleterious actions of heparin binding proteins on the spermatozoa.     

Oligophilic Bacteria as Tools To Monitor Aseptic Pharmaceutical Production Units

The bacterial loads of air, surfaces, and personnel in clean rooms are routinely monitored using a set of standard media. Bacteria that can grow on these media are a tiny fraction of the total numbers in any environment. A substantial proportion of bacteria long thought to be unculturable were recently shown to be oligophilic. Oligophile counts in clean rooms in our studies exceeded the standard plate counts by up to 2 orders of magnitude. They responded to disinfection routines in ways similar to the responses of conventional bacteria. We suggest that oligophiles are better tools than conventional bacteria for environmental monitoring in aseptic pharmaceutical production units.     

Enhancement of mixed leukocyte reaction and cytotoxic antitumor responses by heparin

The immunomodulating effects of heparin and natural and synthetic heparinoids (which are now undergoing clinical trials for the treatment of AIDS) on cellular immunity (DNA synthesis and cytotoxic responses of mouse lymphocytes to allogeneic cells and histocompatible tumors) were studied. The results showed that (1) high and low m.w. heparin enhanced mouse antitumor and antiallogeneic cell responses in vitro; (2) other sulfated heparinoids did not have this enhancing activity and some of them (including dextran sulfate) totally suppressed generation of cytotoxic cells; (3) these immunomodulating activities of heparin and heparinoids did not correlate with their anticoagulant effects, degree of sulfation, and mitogenic activity; (4) heparin did not increase the production of IL-2 and did not enhance the action of IL-2 on the cells in MLC, heparin also had no effect on the growth-promoting activity of IL-2 on cloned cytotoxic T cells; (5) heparin had a synergistic enhancing effect with IL-1 on the generation of cytotoxic cells in MLC; and (6) heparin abolished endothelial cell growth factor-induced suppression of cytotoxic response. The latter two effects by themselves, however, could not fully explain the entire immunoenhancing activity of heparin. These results indicate that heparin and heparinoids have multiple effects on the immune system and that some of them can enhance, whereas others can suppress cell-mediated responses.     

Oligophilic bacteria as tools to monitor aseptic pharmaceutical production units

The bacterial loads of air, surfaces, and personnel in clean rooms are routinely monitored using a set of standard media. Bacteria that can grow on these media are a tiny fraction of the total numbers in any environment. A substantial proportion of bacteria long thought to be unculturable were recently shown to be oligophilic. Oligophile counts in clean rooms in our studies exceeded the standard plate counts by up to 2 orders of magnitude. They responded to disinfection routines in ways similar to the responses of conventional bacteria. We suggest that oligophiles are better tools than conventional bacteria for environmental monitoring in aseptic pharmaceutical production units.     

East-Side story: the standardisation of psychotropic drugs at the Charité Psychiatric Clinic, 1955-1970

The present article illustrates the history of psychotropic drugs introduced in the German Democratic Republic (GDR) from 1945 onwards. We begin by examining the introduction of an anti-depressant and a tranquilizer at the university psychiatric clinic, Charité, in East Berlin. On the basis of patient files, we consider the monitoring routines, altered by the use of psychotropic drugs, and the difficulties that arose when these routines were translated into existing research programs. In the 1960s, attempts to evaluate the psychiatric practice were based on psychopathology whereas at the end of the 1960s there was a shift to “target symptoms”.