Cardiovascular & Haematological Disorders - Drug Targets - Volume 15, Issue 3, 2015

This review starts on one of our special interests, the organ preference of metastasis. We examined data on 1,117 autopsy cases and found that the organ distribution of metastasis of cancers of the lung, pancreas, stomach, colon, rectum, uterine cervix, liver, bile duct, and esophagus involved the lung, liver, adrenal gland, bone/bone marrow, lymph node, and pleura/peritoneum. Cancers of the kidney, thyroid, ovary, choriocarcinoma, and breast, however, manifested different metastatic patterns. The distribution of leukemia and lymphoma metastases was quite different from that of epithelial cancers. On the basis of experimental studies, we believe that the anatomical-mechanical hypothesis should be replaced by the microinjury hypothesis, which suggests that tissue microinjury induced by temporal tumor cell embolization is crucial for successful metastasis. This hypothesis may actually reflect the so-called inflammatory oncotaxis concept. To clarify the mechanisms underlying metastasis, we developed an experimental model system of a rat hepatoma AH7974 that embraced substrate adhesiveness. This model did not prove a relationship between substrateadhesion potential and metastatic lung-colonizing potential of tumor cells, but metastatic potential was correlated with the expression of the laminin carbohydrate that was recognized by Griffonia (Bandeiraea) simplicifolia isolectin G4. Therefore, we investigated the relationship between carbohydrate expression profiles and metastasis and prognosis. We indeed found an intimate relationship between the carbohydrate expression of cancer cells and the progression of malignant tumors, organ preference of metastasis, metastatic potential of tumor cells, and prognosis of patients.

In Italy, each year 500000 couples refer to specialized centers due to reproductive problems. Among them, recurrent pregnancy loss (RPL) represents a problem of great importance, given that it affects up to 5% of women of childbearing age. Infertility, on the other hand, is a condition that currently covers 10-20% of couples of reproductive age, being idiopathic in 20% of cases. Accumulating evidence support the concept that changes of blood coagulation, generically defined as the presence of a thrombophilic state (congenital or acquired), are the basis of 40-70% of cases of multiple abortions or infertility. Several evidences support the hypothesis that endothelial dysfunction, a hallmark of a condition of low-grade inflammation, is one of the earliest manifestations of thrombotic phenomena. To date, it’s believed that, while the antiinflammatory Th2 cytokines (i.e. interleukin-10) can exert a protective role in pregnancy, the pro-inflammatory Th1 ones (i.e. interferon-γ, tumor necrosis factor-α,) have deleterious effects on pregnancy outcome, including fertilization and implantation failure. Moreover, development of many pregnancy complications, first and foremost venous thromboembolism (VTE), recognizes similar mechanism(s). As VTE is the main preventable cause of mortality during pregnancy, thromboprophylaxis is mandatory according to individual VTE risk, influenced by the presence of thrombophilic conditions. In this review, we will analyze the relationship between thrombophilia and pregnancy complications, with particular focus on the role of inflammation. Subsequently, we will consider some issues related to the thromboembolic risk in pregnancy. Finally, the role of thromboprophylaxis in pregnancy will be discussed.

Despite widespread diffusion of pharmacological prophylaxis, deep venous thrombosis (DVT) is still a common cause of morbidity after major orthopedic surgery (total hip replacement - THR- and total knee replacement -TKR). At present, clear evidence has been provided that pharmacological primary prophylaxis with low molecular weight heparin (LMWH) is associated with a significant decrease in the incidence of venous thromboembolism. The main limitation of LMWH prophylaxis however is the need for parenteral administration with a not negligible drop-out of treatment. Newer oral anticoagulants (NAOs) dabigatran, rivaroxaban, apixiban and edoxaban may be valid alternatives in elective surgery. Several studies have demonstrated the efficacy and safety of NAOs after THR and TKR. The research for new compounds and their antidote is under continuous development Aim of this paper was to review the indications and clinical results of DVT prophylaxis with NAO in patients undergoing major orthopaedic surgery.

Our vision of long-term treatment strategies for the prevention of target organ damage and eventually cardiovascular morbidity and mortality in essential arterial hypertension needs to be continually monitored and updated for at least three issues: 1 - the achievement of target pressure required to obtain the expected benefit needs continuous monitoring, a dose adjustment of the drug and, often, the use of combination therapies; 2 - the chronic use of certain drugs, even in combination, is associated with the possible onset of side effects; 3 - increasing of population life expectancy is inevitably associated with in an increase in drugs use with the unavoidable occurrence of adverse drug reactions, some of which can interfere with blood pressure control. These issues, still poorly studied, pose considerable problems in applying proper strategies for prevention. In this review, we will evaluate the goals of antihypertensive therapy, and its weak spots, such as the frequent side effects, that lead to poor therapy compliance. Moreover, we will review the interactions between antihypertensive and drugs used for other common disease, and their importance in not achieving the expected blood pressure reduction.

Objective: To study the effect of exercise preconditioning on adenosine 5’triphosphate (ATP) metabolism in red blood cells and cardiovascular protection against injury induced by isoproterenol in vivo. Methods: Male Sprague Dawley rats (SDR) were each exercised on a treadmill for 15 minutes at 10 m/min and 10% grade (n = 7) (LowEx), or 14 m/min and 22% grade (n = 8) (VigEx). Two hours after the exercise, each rat received a single dose of isoproterenol (30 mg/kg) by subcutaneous (sc) injection. Two separate groups of SDR were used as control: One received no exercise (n = 10) (NoEx) and the other received no exercise and no isoproterenol (n = 11) (NoIso). Serial blood samples were collected over 5 hours for measurement of ATP and its catabolites by a validated HPLC. Hemodynamic recording was collected continuously for the duration of the experiment. Data were analysed using ANOVA and t-tests and difference considered significant at p < 0.05. Results: Exercise pre-conditioning (both LowEx and VigEx) reduced mortality after isoproterenol from 50% to < 30% (p > 0.05). It attenuated the rebound in blood pressure significantly (p < 0.05 between NoEx vs VigEx), attenuated the increase of RBC adenosine 5’-monophosphate (AMP) concentrations induced by isoproterenol, and also decreased the breakdown of ATP to AMP in the RBC ( p < 0.05 vs NoEx). Conclusion: Exercise pre-conditioning decreased the blood pressure rebound and also breakdown of ATP in RBC after isoproterenol which may be exploited further as a drug target for cardiovascular protection and prevention.