Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 14, Issue 1, 2016

There is increasing interest in the possible therapeutic benefits of the gasotransmitter hydrogen sulfide (H2S; sulfide), and drugs which release sulfide are currently being evaluated in both preclinical and clinical studies as treatments for conditions ranging from cancer to cardiovascular disease to inflammation. Sulfide is generally considered to act as a vasodilator, and it is therefore not surprising that the effects of sulfide donors on both systemic and pulmonary hypertension are being examined. In this review, we provide a critical evaluation of both the evidence that H2S may be of benefit in treating systemic and pulmonary hypertension, and of current hypotheses regarding the cellular mechanisms underlying sulfide’s effects on the systemic and pulmonary vascular systems.

The worldwide increasing prevalence of obesity and sedentary lifestyle is the main cause of the rising incidence of T2DM. Due to chronic macrovascular and microvascular complications, T2DM represent a huge socioeconomic burden in the world. Oxidative stress is a key pathogenic mechanism implicated in diabetic coronary artery disease (CAD). Polymorphisms of oxidative stress genes are known to influence oxidative stress levels and are therefore thought to impact CAD pathogenesis. Identifying higher risk groups would be rational, since it would allow better sample selection and thus better results in antioxidant trials. In this review, we summarize the evidence of oxidative stress gene polymorphisms related to the pathogenesis of CAD. Moreover, we provide a review of antioxidants tested in subjects with CAD.

Background: Drug-eluting stents (DES) have been shown to reduce the rate of acute complications and the need for subsequent revascularization in cases where single-vessels are treated. The performance of DES in patients with multivessel disease and complex lesions, however, remains controversial. This study assessed and compared clinical outcomes following single vs. multivessel percutaneous coronary intervention (PCI), using the Supraflex sirolimus-eluting stent (SES), in an all-comers patient population. Methods: We conducted retrospective, multicenter, all-comers, observational study of 995 patients, who underwent either single-vessel PCI (n=769 patients; group-I) or multivessel PCI (n=226 patients; group-II), treated with the biodegradable polymer coated Supraflex SES, between July-2013 and May-2014 at nine different centers in India. Pre-specified primary endpoint, rate of major adverse cardiac events (MACE) [defined as composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and non-target lesion target vessel revascularization (non-TL TVR)], was analyzed during 12 months after the post-index procedure. We also analyzed the incidence of stent thrombosis (ST) as a safety endpoint during the follow-up period, as defined by the Academic Research Consortium (ARC). Results: Of the whole study group, 1,242 lesions were treated in 995 patients (mean age 61.6±10.8 years; 80.0% male) with average stent length of 26.8±9.3 mm. Multivessel PCI patients were older, had a higher prevalence of arterial hypertension, were smoker, had a family history of coronary artery disease, previous stroke and previous PCI compared to single-vessel PCI patients. Follow-up was available in 99.0% (761/769) of patients with single-vessel intervention and 96.9% (219/226) of patients with multivessel intervention at the end of 12 months. In-hospital MACE was similar for both the groups [group-I, 3 (0.4%) vs. group-II, 1 (0.4%); p=1.000]. The observed MACE for group-I and group-II, at 30 days, 6 and 12 months follow-up were 9 (1.2%) vs. 2 (0.9%); p=1.000, 15 (2.0%) vs. 7 (3.2%); p=0.302 and 24 (3.2%) vs. 12 (5.5%); p=0.109, respectively. The cumulative incidence curves for MACE showed no significant differences between the two groups, at the end of 12 months (p=0.109). Conclusion: Our study shows that use of the Supraflex SES in single and multivessel coronary artery disease produces good clinical outcomes during 12 months of follow-up with a low rate of revascularization, despite complex lesion morphology.

This study investigated the effect of antihypertensive therapy with lisinopril on plasma cholesterol concentration and erythrocyte catalase activity in hypertensive patients. We observed, for the first time, significant inverse correlations between systolic blood pressure (BP) and erythrocyte catalase activity and between diastolic BP and erythrocyte catalase activity. Plasma total and low density lipoprotein (LDL) cholesterol as well as triglyceride levels were similar between baseline and 1-, 3-, and 6-month treatment values in the same patients; however, systolic and diastolic BP levels were expectedly reduced after the therapy. Thus, there was no association between BP and lipid-cholesterol metabolism. These findings confirm antihypertensive effect of lisinopril and suggest that erythrocyte catalase is involved in BP control in hypertension and antihypertensive therapy.

This study aims to evaluate the underlying mechanism of action involved in the hypotensive effect of Chamaemulum nobile L. (Cn) aqueous extract on anesthetized Wistar rats. Lyophilized aqueous extract was administered in the jugular vein, arterial blood pressure and heart rate were measured in the carotide artery over 120 min of injection throughout an invasive direct blood pressure measuring procedure. Intravenous bolus injection of aqueous Cn extract at the doses of 50, 100 and 200 mg/kg produced a dose dependent reduction in arterial blood pressure and heart rate (p<0.001). Specific receptor antagonists (Phentolamine, Terazosin and Atropine) and pharmacological agents (N(omega)-Nitro-L-Arginine Methyl Ester and Captopril) were used for determining the underlying mechanism involved in the hypotensive effect of Cn. Only Phentolamine treatment (2 mg/kg) reduced significantly the hypotensive effect of aqueous Cn extract at a dose of 200 mg/kg. Intravenous perfusion of aqueous Cn extract caused a significant reduction of arterial blood pressure (p<0.01) and reduced the hypertensive effect of intravenous injection of norepinephrine at a dose of 1 μg/kg. We conclude that aqueous Cn extract exhibits a hypotensive effect which may be probably due to an alpha adrenergic receptor blockade mechanism.

Objectives: To study the hematological findings of dogs infected with echinococcosis and the possibility of using in vitro reared Echinococcus granulosus excretory-secretory antigen (ES-Ag) as a reagent for serological diagnosis of canine echinococcosis. Methods: Eight dogs were infected orally with protoscoleces, extracted from ovine fertile hydatid cysts. Two additional dogs were infected with Cysticercus tenuicollis, obtained from infested sheep. The hematological parameters of dogs were determined with the ADVIA 2120i automatic hematology analyzer with a blood smear staining module. Adult E. granulosus and/or Taenia hydatigena that were collected from small pieces of the open gut and the larval cestodes that were extracted from infested sheep during slaughter were cultured in an incomplete RPMI-1640 medium. The parasite-ES-Ag-containing supernatant was used as an antigen in enzyme linked immunosorbent assay (ELISA) to detect antibodies in the sera of infected dogs. Results: A significant increase in hemoglobin concentration and erythrocyte count was found during the infection, as well as an increasing proportion of lymphocytes and segmented neutrophils, accompanied by a significant reduction of the leukocyte count and a growth of both the absolute and the relative eosinophil count. ELISA found a strengthening antigenicity of echinococcus preparations during infection. This property was more pronounced in the protoscoleces ES-Ag, compared to the eponymous antigen of an adult parasite. The latter gave specificity to ELISA, which allowed differentiating it from the similar antigen of the closely related tapeworm T. hydatigena. Conclusion: In vitro reared adult E. granulosus ES-Ag can be used as an antigen in the serological diagnosis of canine echinococcosis. Hematological parameters and serological results have predictive value in the screening of dogs for echinococcosis; however, in some individuals, they may reflect the state of resistance to invasion.

Background: More than 50% of oncohematological patients suffer from pain syndrome, mostly originating from the bone, which often include nociceptive and neuropathic complaints. Tapentadol, a recently available treatment option for cancer pain, exerts a dual analgesic mechanisms (opioid and noradrenergic), allowing for a high clinical efficacy as well as for a reduction in adverse events compared to traditional opioids. Aim: To explore the safety and efficacy of tapentadol as a suitable agent for the pain management in the setting of oncohematology. Methods: Our observational study included 36 patients with basal pain intensity (NRS) ranging from 5 to 10. Tapentadol prolonged release (PR) was given at the initial dose of 50 mg BID and careful titrated according to the achieved pain control. Results. Tapentadol PR was given at the dosages ranging from 200 and 260 mg/day after a careful titration, allowed for a clinically (-7 points NRS) remarkable reduction of pain intensity without any significant side effects. Conclusion: In oncohematological patients on pain, tapentadol PR was effective and well tolerated, so representing a suitable treatment option in this difficult setting.