Diagnosis and management of type II myocardial infarction: increased demand for a limited supply of evidence.

Type 2 myocardial infarction (type 2 MI) is defined as myocardial necrosis that results from an imbalance of myocardial oxygen supply and demand. Although type 2 MI is highly prevalent and strongly associated with mortality, the pathophysiology remains poorly understood. Discrepancies in definitions, frequency of screening, diagnostic approaches, and methods of adjudication lead to confusion and misclassification. To date, there is no consensus on the diagnostic criteria for type 2 MI. No guidelines exist for the optimal management of this condition, and further investigation is urgently needed. This review explores the existing evidence on the pathophysiology, diagnosis, prognosis, and management of type 2 MI.

Efficacy of tranexamic acid in the treatment of idiopathic and non-functional heavy menstrual bleeding: a systematic review.

OBJECTIVE: To evaluate the efficacy of tranexamic acid in the treatment of idiopathic and non-functional heavy menstrual bleeding. DESIGN: Systematic review. POPULATION: Women with a diagnosis of idiopathic and non-functional heavy menstrual bleeding treated with tranexamic acid. METHODS: Electronic searches were conducted in literature databases up to February 2011 by two independent reviewers. We included all trials involving the efficacy of tranexamic acid for the treatment of heavy uterine bleeding. Pregnant, postmenopausal and cancer patients were excluded. MAIN OUTCOME MEASURES: Effect of tranexamic acid treatment on objective reduction of menstrual bleeding and improvement in patient quality of life. RESULTS: A total of 10 studies met our inclusion criteria. Available evidence indicates that tranexamic acid therapy in women with idiopathic menorrhagia resulted in 34-54% reduction in menstrual blood loss. Following tranexamic acid treatment, patient's quality-of-life parameters improved by 46-83%, compared with 15-45% for norethisterone treatment. When compared with placebo, tranexamic acid use significantly decreased the blood loss by 70% in women with menorrhagia secondary to an intrauterine device (p<0.001). Limited evidence indicated potential benefit in fibroid patients with menorrhagia. No thromboembolic event was reported in all studies analyzed. CONCLUSIONS: Available evidence indicates that tranexamic acid treatment is effective and safe, and could potentially improve quality of life of patients presenting with idiopathic and non-functional heavy menstrual bleeding. Data on the therapeutic efficacy of tranexamic acid in patients with symptomatic fibroids are limited, and further studies are therefore needed.

Synthesis, characterization, and in vitro antimalarial and antitumor activity of new ruthenium(II) complexes of chloroquine.

The new Ru(II) chloroquine complexes [Ru(eta(6)-arene)(CQ)Cl2] (CQ = chloroquine; arene = p-cymene 1, benzene 2), [Ru(eta(6)-p-cymene)(CQ)(H2O)2][BF4]2 (3), [Ru(eta(6)-p-cymene)(CQ)(en)][PF6]2 (en = ethylenediamine) (4), and [Ru(eta(6)-p-cymene)(eta(6)-CQDP)][BF4]2 (5, CQDP = chloroquine diphosphate) have been synthesized and characterized by use of a combination of NMR and FTIR spectroscopy with DFT calculations. Each complex is formed as a single coordination isomer: In 1-4, chloroquine binds to ruthenium in the eta(1)-N mode through the quinoline nitrogen atom, whereas in 5 an unprecedented eta(6) bonding through the carbocyclic ring is observed. 1, 2, 3, and 5 are active against CQ-resistant (Dd2, K1, and W2) and CQ-sensitive (FcB1, PFB, F32, and 3D7) malaria parasites (Plasmodium falciparum); importantly, the potency of these complexes against resistant parasites is consistently higher than that of the standard drug chloroquine diphosphate. 1 and 5 also inhibit the growth of colon cancer cells, independently of the p53 status and of liposarcoma tumor cell lines with the latter showing increased sensitivity, especially to 1 (IC50 8 microM); this is significant because this type of tumor does not respond to currently employed chemotherapies.

The mechanism of antimalarial action of the ruthenium(II)-chloroquine complex [RuCl(2)(CQ)] (2).

The mechanism of antimalarial action of the ruthenium-chloroquine complex [RuCl(2)(CQ)](2) (1), previously shown by us to be active in vitro against CQ-resistant strains of Plasmodium falciparum and in vivo against P. berghei, has been investigated. The complex is rapidly hydrolyzed in aqueous solution to [RuCl(OH(2))(3)(CQ)](2)[Cl](2), which is probably the active species. This compound binds to hematin in solution and inhibits aggregation to beta-hematin at pH approximately 5 to a slightly lower extent than chloroquine diphosphate; more importantly, the heme aggregation inhibition activity of complex 1 is significantly higher than that of CQ when measured at the interface of n-octanol-aqueous acetate buffer mixtures under acidic conditions modeling the food vacuole of the parasite. Partition coefficient measurements confirmed that complex 1 is considerably more lipophilic than CQ in n-octanol-water mixtures at pH approximately 5. This suggests that the principal target of complex 1 is the heme aggregation process, which has recently been reported to be fast and spontaneous at or near water-lipid interfaces. The enhanced antimalarial activity of complex 1 is thus probably due to a higher effective concentration of the drug at or near the interface compared with that of CQ, which accumulates strongly in the aqueous regions of the vacuole under those conditions. Furthermore, the activity of complex 1 against CQ-resistant strains of P. falciparum is probably related to its greater lipophilicity, in line with previous reports indicating a lowered ability of the mutated transmembrane transporter PfCRT to promote the efflux of highly lipophilic drugs. The metal complex also interacts with DNA by intercalation, to a comparable extent and in a similar manner to uncomplexed CQ and therefore DNA binding does not appear to be an important part of the mechanism of antimalarial action in this case.