Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 8, Issue 2, 2010

The pathophysiology of preeclampsia (PE), a disorder occurring in 5% of all pregnancies, remains largely unknown, but early placental hypoxia and oxidative stress are known to be involved in the mechanism of the syndrome. Maternal plasma and placental tissue samples were collected from PE, intrauterine growth restriction (IUGR), and normotensive pregnant patients. The immunohistochemical expression of vascular endothelial growth factor (VEGF), malondialdehyde (MDA) production and the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase GSH-Px) were determined in the placental tissue. F2-isoprostane concentration and the ferric reducing ability of plasma (FRAP) were determined in maternal plasma. We found that the PE and IUGR groups showed a higher expression of VEGF in the muscular layer of fetal chorionic vessels. In addition, increased plasma F2 isoprostane levels and a significant reduction of FRAP in the plasma of PE women, as well as a lower activity of SOD in PE placentas and a higher activity of GSH-Px in IUGR placentas were found. Additionally, lower PlGF and higher sFlt1 levels were observed in the maternal plasma of PE and IUGR than control. We concluded that in a hypoxic environment, the placenta expresses VEGF in the muscular layer of fetal vessels. The development of PE could be related to the increased expression of VEGF, with decreased placental SOD activity and a decrease of both plasma F2-isoprostane and FRAP levels. In turn, the development of IUGR could be related to the association of decreased plasma FRAP levels and increased placental GSH-Px activity.

Anticoagulants are the mainstay of treatment of venous thromboembolic and acute coronary events. Improvements of new over established anticoagulants are targeted to achieve more favorable pharmacokinetics, minimal hemorrhagic side effects, a predictable dose response that obviates the need for coagulation monitoring, and more appropriate dose selection for the indication of interest. New parenteral anticoagulants are free of the complications of HIT, can be selected so that they are safe in patients with impaired renal or hepatic function, and can be administered once daily without the need for coagulation monitoring. Drug development has been focused on two key targets: factor Xa and factor IIa (thrombin). Fondaparinux is the first selective inhibitor of the coagulation factor Xa which is commercially available for clinical use. It has been approved for the prevention of venous thromboembolism in patients undergoing orthopedic surgery, abdominal surgery and for the initial therapy of deep venous thrombosis and venous thromboembolism. Fondaparinux sodium injection has been accepted for priority review by the United States Food and Drug Administration based on positive results from two pivotal, Phase III trials (OASIS 5 and 6) that evaluated its role in the treatment of a broad spectrum of patients with acute coronary syndromes (ACS). In this article, we review the available literature that provides evidence for the efficacy of fondaprinux in management of thromboembolic disease as well as acute coronary syndromes.

Nitric oxide (NO) is a short-lived intercellular messenger with multiple biological implications, such as regulation of blood pressure, inhibition of platelet adhesion and aggregation, bacterial-challenge and cytokine stimulation, and regulation of mineralized tissue function. NO synthase (NOS) catalyses the conversion of cationic amino acid L-arginine to L-citrulline and NO. Recently there is an increasing interest in the role of NO in the physiopathology of periodontal disease (PD). PD is a chronic inflammatory disease of the attachment structures of the teeth, which is found in 40-50% of most adult populations worldwide and may result in tooth loss. The potential sources of NO in periodontum are inflammatory cells, keratinocytes, fibroblasts, osteoclastics and blood vessels. Etiological periodontitis factors, such as inflammatory cytokines and periodontopathogens are evolved in enhanced NO levels, which may be part of a nonspecific natural defense mechanism or may lead to periodontal damage. This review gives detail of recent research data focusing on NO bioavailability and its involvement in periodontitis pathogenesis and the modulation of NO for better control of this disease.

The objective of this study was to evaluate the scientific evidence on stevia, including expert opinion, folkloric precedent, history, pharmacology, kinetics/dynamics, interactions, adverse effects, toxicology, and dosing. This review serves as a clinical support tool. Electronic searches were conducted in 10 databases, 20 additional journals (not indexed in common databases), and bibliographies from 50 selected secondary references. No restrictions were placed on the language or quality of the publications. All literature collected pertained to efficacy in humans, dosing, precautions, adverse effects, use in pregnancy and lactation, interactions, alteration of laboratory assays, and mechanisms of action. Standardized inclusion and exclusion criteria were used for selection. Grades were assigned using an evidence-based grading rationale. Based on the availability of scientific data, two indications are discussed in this review: hypertension and hyperglycemia. Evaluation of two long-term studies (1 and 2 years in length, respectively) indicates that stevia may be effective in lowering blood pressure in hypertensive patients, although data from shorter studies (1-3 months) did not support these findings. A pair of small studies also report positive results with respect to glucose tolerance and response, although the relatively low methodological rigor of these experiments limits the strength of these findings. Further investigation is warranted in both indications.