The metabolism and significance of homocysteine in nutrition and health.

An association between arteriosclerosis and homocysteine (Hcy) was first demonstrated in 1969. Hcy is a sulfur containing amino acid derived from the essential amino acid methionine (Met). Hyperhomocysteinemia (HHcy) was subsequently shown in several age-related pathologies such as osteoporosis, Alzheimer's disease, Parkinson's disease, stroke, and cardiovascular disease (CVD).

The Nitric Oxide Pathway in Pulmonary Vascular Disease.

Nitric oxide is an endogenous pulmonary vasodilator that is synthesized from L-arginine in pulmonary vascular endothelial cells by nitric oxide synthase and diffuses to adjacent vascular smooth muscle cells where it activates soluble guanylyl cyclase. This enzyme converts GTP to cGMP which activates cGMP dependent protein kinase leading to a series of events that decrease intracellular calcium and reduce vascular muscle tone. Nitric oxide is an important mediator of pulmonary vascular tone and vascular remodeling.

Analysis of decreases in systemic arterial pressure and heart rate in response to the hydrogen sulfide donor sodium sulfide.

The actions of hydrogen sulfide (HS) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of HS are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of HS on the electrocardiogram and examine the relationship between HS-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function.

Aging and sexual health: getting to the problem.

Erectile dysfunction (ED) is one of the most common disorders in male and is often associated with other age-related comorbidities. The aging process affects the structural organization and function of penile erectile components such as smooth muscle cell and vascular architecture. These modifications affect penile hemodynamics by impairing cavernosal smooth muscle cell relaxation, reducing penile elasticity, compliance and promoting fibrosis.

Current therapies for premature ejaculation.

Premature ejaculation (PE) subjectively affects 20-30% of men globally. Until recently, understanding of PE was hampered by the absence of a widely accepted definition, paucity of evidence-based clinical studies, and the absence of an appropriate animal model. Here, we elaborate on the current definition of PE, its pathogenesis, currently available therapies, and future treatment prospects.

Mirabegron causes relaxation of human and rat corpus cavernosum: could it be a potential therapy for erectile dysfunction?

Objective: To examine the effects of mirabegron, a selective β3 -adrenoceptor agonist that has recently been approved for the treatment of overactive bladder (OAB), on erectile function. Stimulation of β3 -adrenoceptors localised in cavernosal smooth muscle cells may play a physiological role in mediating penile erection, and offer a beneficial pharmacological action for patients who have OAB and erectile dysfunction (ED).

Materials And Methods: Corpus cavernosal (CC) specimens were obtained from patients with ED and Peyronie's disease undergoing penile prosthesis implantation.

Overview of potential molecular targets for hydrogen sulfide: A new strategy for treating erectile dysfunction.

Hydrogen sulfide (HS) is a molecule of increasing interest in biology. It is now recognized as the third most important biological gasotransmitter after nitric oxide (NO) and carbon monoxide (CO); it freely diffuses across cellular membranes and affects various physiologic functions. There are functional roles for HS in sexual medicine related to cavernosal smooth muscle relaxation and the erectile mechanism.

The impact of statins on biological characteristics of stem cells provides a novel explanation for their pleiotropic beneficial and adverse clinical effects.

Statins reduce atherosclerotic events and cardiovascular mortality. Their side effects include memory loss, myopathy, cataract formation, and increased risk of diabetes. As cardiovascular mortality relates to plaque instability, which depends on the integrity of the fibrous cap, we hypothesize that the inhibition of the potential of mesenchymal stem cells (MSCs) to differentiate into macrophages would help to explain the long known, but less understood "non-lipid-associated" or pleiotropic benefit of statins on cardiovascular mortality.

Analysis of erectile responses to H2S donors in the anesthetized rat.

Hydrogen sulfide (H2S) is a biologically active endogenous gasotransmitter formed in penile tissue that has been shown to relax isolated cavernosal smooth muscle. In the present study, erectile responses to the H2S donors sodium sulfide (Na2S) and sodium hydrosulfide (NaHS) were investigated in the anesthetized rat. Intracavernosal injections of Na2S in doses of 0.

Intratunical Injection of Genetically Modified Adipose Tissue-Derived Stem Cells with Human Interferon α-2b for Treatment of Erectile Dysfunction in a Rat Model of Tunica Albugineal Fibrosis.

Introduction: Peyronie's disease (PD) has frequently been associated with erectile dysfunction (ED) and may further compromise coitus.

Aim: To investigate the efficacy of intratunical injection of genetically modified rat adipose tissue-derived stem cells (ADSCs) expressing human interferon α-2b (ADSCs-IFN) in decreasing fibrosis and restoring erectile function in a rat model of tunica albugineal fibrosis (TAF).

Methods: A total of 36 Sprague-Dawley rats (12 weeks old; 300-350 g) were randomly divided in six equal groups: (i) sham group (50 μL saline-injected into the tunica albuginea [TA]); (ii) TAF group (transforming growth factor [TGF]-β1 [0.

Analysis of erectile responses to bradykinin in the anesthetized rat.

The kallikrein-kinin system is expressed in the corpus cavernosa, and bradykinin (BK) relaxes isolated corpora cavernosal strips. However, erectile responses to BK in the rat have not been investigated in vivo. In the present study, responses to intracorporal (ic) injections of BK were investigated in the anesthetized rat.

Efficacy of pioglitazone on erectile function recovery in a rat model of cavernous nerve injury.

Objective: To examine the effect of pioglitazone on erectile function in a rat model of postprostatectomy erectile dysfunction.

Methods: Twenty adult rats were divided into 4 groups: (a) sham, (b) control--bilateral cavernosal nerve crush injury (BCNI), (c) BCNI + low-dose pioglitazone (PioL), and (d) BCNI + high-dose pioglitazone (PioH). Sham and control rats were administered phosphate-buffered saline, whereas PioL and PioH rats received 0.

2015 update of erectile dysfunction management following radical prostatectomy: from basic research to clinical management.

Radical prostatectomy (RP) is the most commonly employed curative intervention for the treatment of prostate cancer. However, due to the proximity of the cavernous nerves (CN) to the prostate, RP results in transient and/often permanent erectile dysfunction (ED). While the prevention of traction injuries during the RP is critical for the preservation of erectile function, several preclinical studies have demonstrated the beneficial effects of neuroprotective (or neuroregenerative) agents in mitigating neuronal injuries sustained during RP.

Intratracheal administration of cyclooxygenase-1-transduced adipose tissue-derived stem cells ameliorates monocrotaline-induced pulmonary hypertension in rats.

The effect of intratracheal administration of cyclooxygenase-1 (COX-1)-modified adipose stem cells (ASCs) on monocrotaline-induced pulmonary hypertension (MCT-PH) was investigated in the rat. The COX-1 gene was cloned from rat intestinal cells, fused with a hemagglutanin (HA) tag, and cloned into a lentiviral vector. The COX-1 lentiviral vector was shown to enhance COX-1 protein expression and inhibit proliferation of vascular smooth muscle cells without increasing apoptosis.

Vasodilator responses to acetylcholine are not mediated by the activation of soluble guanylate cyclase or TRPV4 channels in the rat.

The effects of 1H-[1,2,4]-oxadizaolo[4,3-]quinoxaline-1-one (ODQ), an inhibitor of the activation of soluble guanylate cyclase (sGC) on responses to NO donors acetylcholine (ACh) and bradykinin (BK) were investigated in the pulmonary and systemic vascular beds of the rat. In these studies the administration of ODQ in a dose of 5 mg/kg iv attenuated vasodilator responses to five different NO donors without inhibiting responses to ACh and BK in the systemic and pulmonary vascular beds of the rat. Vasodilator responses to ACh were not inhibited by l-NAME or the transient receptor vanilloid type 4 (TRPV4) antagonist GSK-2193874, which attenuated vasodilator responses to the TRPV4 agonist GSK-1016790A.

Mechanism of endoplasmic reticulum stress-induced vascular endothelial dysfunction.

Background: We recently reported that ER stress plays a key role in vascular endothelial dysfunction during hypertension. In this study we aimed to elucidate the mechanisms by which ER stress induction and oxidative stress impair vascular endothelial function.

Methodology/principal Findings: We conducted in vitro studies with primary endothelial cells from coronary arteries stimulated with tunicamycin, 1μg/mL, in the presence or absence of two ER stress inhibitors: tauroursodeoxycholic acid (Tudca), 500μg/mL, and 4-phenylbutyric acid (PBA), 5mM.

Angina pectoris: current therapy and future treatment options.

Angina pectoris is the consequence of an inequality between the demand and supply of blood to the heart. Angina manifests itself as chest pain or discomfort and is a common complaint of patients in the hospital and in the clinic. There are, in fact, roughly half a million new cases of angina per year.

The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction.

Objective: To determine the effect of avanafil, a novel phosphodiesterase-5 inhibitor, on the treatment of erectile dysfunction associated with type 2 diabetes mellitus (T2DM).

Methods: In 2-day-old rats, T2DM was induced by single intraperitoneal injection of 90 mg/kg of streptozotocin (STZ; i.p.

Review of erectile dysfunction in diabetic animal models.

Erectile dysfunction (ED) is a common, male sexual disorder that has a negative impact on the quality of life of men and their sexual partners. The prevalence of ED in diabetic men is ≥ 50%. Animal models provide a valuable perspective in the investigation of ED.

Analysis of responses to the TRPV4 agonist GSK1016790A in the pulmonary vascular bed of the intact-chest rat.

The transient receptor potential vanilloid 4 (TRPV4) channel is a nonselective cation channel expressed on many cell types, including the vascular endothelium and smooth muscle cells. TRPV4 channels play a role in regulating vasomotor tone and capillary permeability. The present study was undertaken to investigate responses to the TRPV4 agonist GSK101790A on the pulmonary and systemic vascular beds in the rat.

Imatinib attenuates monocrotaline pulmonary hypertension and has potent vasodilator activity in pulmonary and systemic vascular beds in the rat.

Cardiovascular responses to the tyrosine kinase inhibitor imatinib were investigated in the rat. Intravenous injections of 0.3-30 mg/kg imatinib produced small decreases in pulmonary arterial pressure, larger dose-dependent decreases in systemic arterial pressure, and no change or small increases in cardiac output, suggesting that the systemic vasodilator response is more pronounced under baseline conditions.

A review of current therapies used in the treatment of congestive heart failure.

Congestive heart failure is the leading cause of hospitalizations for patients older than 65 years. There are almost 700,000 new cases of heart failure annually and re-hospitalization rates are as high as 50% within the first few months of initial discharge. These statistics translate to healthcare costs that nearly reached US$40 billion in 2010.