Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Invasive and antiplatelet treatment of patients with non‐ST‐segment elevation myocardial infarction: Understanding and addressing the global risk‐treatment paradox

Clinical guidelines for the treatment of patients with non‐ST‐segment elevation myocardial infarction (NSTEMI) recommend an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization. However, although patients with NSTEMI have a higher long‐term mortality risk than patients with ST‐segment elevation myocardial infarction (STEMI), they are often treated less aggressively; with those who have the highest ischemic risk often receiving the least aggressive treatment (the “treatment‐risk paradox”). Here, using evidence gathered from across the world, we examine some reasons behind the suboptimal treatment of patients with NSTEMI, and recommend approaches to address this issue in order to improve the standard of healthcare for this group of patients. The challenges for the treatment of patients with NSTEMI can be categorized into four “P” factors that contribute to poor clinical outcomes: patient characteristics being heterogeneous; physicians underestimating the high ischemic risk compared with bleeding risk; procedure availability; and policy within the healthcare system. To address these challenges, potential approaches include: developing guidelines and protocols that incorporate rigorous definitions of NSTEMI; risk assessment and integrated quality assessment measures; providing education to physicians on the management of long‐term cardiovascular risk in patients with NSTEMI; and making stents and antiplatelet therapies more accessible to patients.     

Ticagrelor Versus Clopidogrel in Patients With STEMI Treated With Fibrinolysis: TREAT Trial

BackgroundThe efficacy of ticagrelor in the long-term post–ST-segment elevation myocardial infarction (STEMI) treated with fibrinolytic therapy remains uncertain.ObjectivesThe purpose of this study was to evaluate the efficacy of ticagrelor when compared with clopidogrel in STEMI patients treated with fibrinolytic therapy.MethodsThis international, multicenter, randomized, open-label with blinded endpoint adjudication trial enrolled 3,799 patients (age <75 years) with STEMI receiving fibrinolytic therapy. Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg daily thereafter). The key outcomes were cardiovascular mortality, myocardial infarction, or stroke, and the same composite outcome with the addition of severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events at 12 months.ResultsThe combined outcome of cardiovascular mortality, myocardial infarction, or stroke occurred in 129 of 1,913 patients (6.7%) receiving ticagrelor and in 137 of 1,886 patients (7.3%) receiving clopidogrel (hazard ratio: 0.93; 95% confidence interval: 0.73 to 1.18; p = 0.53). The composite of cardiovascular mortality, myocardial infarction, stroke, severe recurrent ischemia, transient ischemic attack, or other arterial thrombotic events occurred in 153 of 1,913 patients (8.0%) treated with ticagrelor and in 171 of 1,886 patients (9.1%) receiving clopidogrel (hazard ratio: 0.88; 95% confidence interval: 0.71 to 1.09; p = 0.25). The rates of major, fatal, and intracranial bleeding were similar between the ticagrelor and clopidogrel groups.ConclusionAmong patients age <75 years with STEMI, administration of ticagrelor after fibrinolytic therapy did not significantly reduce the frequency of cardiovascular events when compared with clopidogrel. (Ticagrelor in Patients With ST Elevation Myocardial Infarction Treated With Pharmacological Thrombolysis [TREAT]; NCT02298088)     

Non-ST elevation acute coronary syndrome: changes of parameters of hemostasis during and after treatment with unfractionated heparin and enoxaparin

AIM: To compare changes of parameters of hemostasis in patients with non-ST elevation acute coronary syndrome (NSTEACS) during and after treatment with unfractionated heparin (UFH) and low molecular weight heparin (LMWH) enoxaparin. MATERIAL: Control groups of 2 randomized studies of effects of thienopyridines in NSTEACS with similar inclusion criteria. METHODS: In patients (n=18) of study one UFH was infused intravenously for 54.2+/-22.3 h, in patients of study two subcutaneous enoxaparin 1 mg/kg b.i.d. was used for 76.2+/-28.3 h. Levels of D-dimer (DD), thrombin-antithrombin complex (TAT), prothrombin fragment 1+2 (F1+2), von Willebrand factor (vWF), fibrinogen, tissue plasminogen activator (TPA) and activity of its inhibitor (PAI), soon after start of treatment with heparins and in 1, 3, 7 and 14 days. RESULTS AND CONCLUSION: Short term lowering of DD and TAT levels occurred during UFH infusion apparently reflecting primary antithrombin action of UFH. During LMWH use DD level remained unchanged however its lowering was observed after cessation of LMWH (on days 7 and 14). The use of LMWH was not associated with increases of thrombinemia (TAT), thrombin generation (F1+2), and fibrinogen which were registered after end of UFH infusion (days 3, 7 and 14). Neither UFH nor LMWH prevented acute phase vWF elevation. The use of both heparins was associated with changes that could be interpreted as profibrinolytic. In LMWH treated patients these changes (elevations of TPA level) became manifested early (on day 3) and were short lived while in UFH treated patients they appeared later (on day 7) and were prolonged (as lowered PAI activity on day 14).     

Feasibility of implementation of guidelines for the management of acute coronary syndrome in cardiac unit of a community hospital

AIM: To assess feasibility of implementation of Guidelines of Russian Society of Cardiology (RSC) on the management of non ST elevation acute coronary syndrome (adaptation of Guidelines of the European Society of Cardiology) in an ordinary noninvasive community hospital. METHODS: Retrospective analysis of inhospital management of 266 consecutive patients with acute coronary syndromes without persistent ST elevation admitted to coronary unit of a community hospital in January-July, 2001. MATERIAL AND RESULTS: Main characteristics of the group: mean age 69 years (34% >75 years), men - 56%, history of myocardial infarction - 38%, hypertension - 67%, diabetes - 23%, pain at rest as an index event - 98%, symptoms duration exceeding 20 min - 61%, ECG changes - 87% (42% ST deviation), signs of left ventricular failure - 14%. Myocardial infarction as index event was diagnosed in 32% of pts by serial measurement of total CK activity. There were no angiographies or revascularizations during hospital stay (20-/+6 days) because of absence of catheterization facilities. Medical treatment: antiplatelet agents - 99% (98% - aspirin) of patients; proportion of patients treated with heparins - 83% (low molecular weight heparins - 18,5%). Most of the patients received b-blockers (79%) and nitrates (78%). Use of calcium channel blockers was relatively low (15%). Few patients (20%) received statins. Inhospital rate of death and nonfatal myocardial infarction was 3,5% i 3%, respectively. Rate of chest pain recurrence was high (38% overall, 26% with ischemic ST-T ECG changes) and at least partially could be explained by the lack of invasive interventions. CONCLUSION: Management of patients with non ST elevation ACS in coronary unit of a community hospital during the period surveyed in this study was in line with corresponding RSC guidelines (as related to noninvasive treatment) except duration of hospitalization. This was associated with acceptable rate of death or/and myocardial infarction (6,5%) in a group of relatively high risk pts. High rate of angina recurrences during rather long hospital stay reflected absence of invasive treatment.     

Evasin‐3‐like anti‐chemokine activity in salivary gland extracts of ixodid ticks during blood‐feeding: a new target for tick control

Ticks exploit many evasion mechanisms to circumvent the immune control of their hosts including subversion of the communication language between cells of the immune system provided by chemokines and other cytokines. One subversive molecule secreted in the saliva of Rhipicephalus sanguineus is Evasin‐3, a structurally unique 7 kDa protein that selectively binds the neutrophil chemoattractants, CXCL8 and (with lower affinity) CXCL1. We compared anti‐human CXCL8 and anti‐mouse CXCL1/KC activities in salivary gland extracts prepared from adult Amblyomma variegatum, Rhipicephalus appendiculatus and Dermacentor reticulatus ticks during blood‐feeding. Both anti‐CXCL8 activity and anti‐CXCL1 activity were detected in all species and in both adult females and males, with consistently higher activity levels against CXCL8. These results suggest that Evasin‐3‐like activity is common amongst metastriate ixodid tick species, and provide further evidence of the importance to ticks in controlling neutrophils during blood‐feeding. As such, Evasin‐3 offers a new target for anti‐tick vaccine development.     

Unstable angina: tissue plasminogen activator, tissue plasminogen activator inhibitors, protein C and other factors of the blood fibrinolytic system]

The authors examined the activities of plasminogen activator, its inhibitor, the levels of C protein, antithrombin III, alpha 2-antiplasmin, plasminogen, fibrinogen, fibrinogen/fibrin degradation products in 22 patients with unstable angina by using the vein occlusive test. No significant differences were found in the examined parameters while comparing the group of stable angina patients and healthy subjects. It was concluded that thrombogenesis disturbances in unstable angina were regional and the recording of peripheral blood fibrinolytic parameters failed to detect any changes characteristic of unstable angina.