Diabetic nephropathy: Treatment with phosphodiesterase type 5 inhibitors.

The importance of nitric oxide (NO) in vascular physiology is irrefutable; it stimulates the intracellular production of cyclic guanosine monophosphate (cGMP), initiating vascular smooth muscle relaxation. This biochemical process increases the diameter of small arteries, regulating blood flow distribution between arterioles and the microvasculature. The kidney is no exception, since NO predominantly dilates the glomerular afferent arterioles.

Angiotensin II increases corpus cavernosal contractility and oxidative stress in partial bladder outlet obstructed rabbits: relevance to erectile dysfunction.

Introduction: We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells.

Aim: To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO.

Methods: Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits.

Effect of angiotensin II and its receptor antagonists on human corpus cavernous contractility and oxidative stress: modulation of nitric oxide mediated relaxation.

Purpose: To our knowledge the interaction between angiotensin II and nitric oxide in the control of human corpus cavernous function has not been assessed previously. We determined the presence and role of angiotensin II and its receptors in human penile function.

Materials And Methods: Corpus cavernous tissue was obtained from 35 patients undergoing gender reassignment surgery.

Animal models of diabetes mellitus: relevance to vascular complications.

The prevalence of diabetes mellitus is increasing worldwide at an alarming rate due to population growth, obesity, sedentary lifestyle and aging. Consequently, diabetic microvascular complications (retinopathy and nephropathy) and macrovascular complications (coronary heart disease, peripheral arterial disease and cerebrovascular disease) are also rising. Traditional oral hypoglycaemic agents only partially prevent the development of these complications.

A functional study of purinergic signalling in the normal and pathological rabbit corpus cavernosum.

Objective: To examine rabbit cavernosal smooth muscle (CSM) relaxation to ATP, ADP and UTP in normal rabbits and in models of conditions that predispose to erectile dysfunction (ED), diabetes mellitus (DM; induced for 6 months) and bladder outlet obstruction (BOO, 6 weeks after surgery).

Materials And Methods: Concentration-response curves (CRCs) were constructed to ATP, ADP and UTP on CSM from control rabbits in the absence and presence of antagonists. In addition, CRCs were constructed to ATP in CSM from rabbits with DM and BOO.

The effect of vardenafil (a PDE type 5 inhibitor) on renal function in the diabetic rabbit: a pilot study.

Background: Diabetic nephropathy is a common cause of impaired renal function. We investigated the effect vardenafil, a phosphodiesterase type 5 (PDE-5) inhibitor, has on renal function in the diabetic rabbit.

Materials And Methods: Blood was taken at 4 and 6 months from control and alloxan-induced diabetic animals (n=8, in each group) and biochemical variables pertaining to renal function determined.

Serotonin induces a biphasic response in rabbit cavernosal smooth muscle: relevance to the erectile process.

Introduction: Serotonin (5-hydroxytryptamine; 5-HT) can cause contraction in cavernosal smooth muscle. We further evaluated this effect of 5-HT.

Methods: Organ bath studies were used.

The role of serotonin (5-hydroxytryptamine1A and 1B) receptors in prostate cancer cell proliferation.

Purpose: Serotonin (5-hydroxytryptamine), a monoamine neurotransmitter released by prostate neuroendocrine cells, has a fundamental role in tumor growth, differentiation and gene expression. We investigated the effect of 5-hydroxytryptamine and 5-hydroxytryptamine antagonists on the growth of prostate cancer cells and we identified 5-hydroxytryptamine receptor expression in PC3 cells and in human hormone refractory prostate cancer tissue.

Materials And Methods: A total of 12 preparations of hormone refractory PC3 human prostate cancer cells were incubated with 5-hydroxytryptamine, or the 5-hydroxytryptamine receptor antagonists 5-hydroxytryptamine1A, 1B, 1D, 2, 3 or 4.

Gene therapy and erectile dysfunction: the current status.

Current available treatment options for erectile dysfunction (ED) are effective but not without failure and/or side effects. Although the development of phosphodiesterase type 5 (PDE5) inhibitors (i.e.

Doxazosin and serotonin (5-HT) receptor (1A, 2A, and 4) antagonists inhibit 5-HT-mediated human cavernosal contraction.

Penile erection results from the balance between relaxation and contractile mechanisms of the corpus cavernosum. Only a few studies suggest a role for endogenous contractile agents such as 5-hydroxytryptamine (5-HT). Our aim was to confirm the possible role of 5-HT in human erection.

Pharmacological properties of endothelin-1 in the rabbit corpus cavernosum.

Background: Endothelin (ET-1) may play a role in the regulation of erection but this has not been conclusively demonstrated. Augmented cavernosal smooth muscle (CSM) contraction in the rat occurs following exposure to both ET-1 and phenylephrine (PE; alpha-1 agonist). The aim of this study was to assess the effect of ET-1 and its possible role in the alpha1-adrenergic pathway during the erectile process.

The management of phosphodiesterase-5 (PDE5) inhibitor failure.

The oral phosphodiesterase type 5 (PDE5) inhibitors have made a valuable contribution to the treatment of erectile dysfunction (ED). PDE5 inhibitors enhance cavernosal smooth muscle relaxation, vasodilatation and penile erection. However, PDE5 inhibitors are not always effective.

The purinergic component of human vas deferens contraction.

Objective: To examine purinergic signaling in human vas deferens.

Design: To study contractile responses of the scrotal vas deferens.

Setting: Research department of a university teaching hospital.

The effect of serotonin and serotonin antagonists on bladder cancer cell proliferation.

Objective: To investigate the role of serotonin (5-hydroxytryptamine, 5HT) and its antagonists in the proliferation of high-grade bladder cancer cells (HT1376), as high-grade bladder cancer has a rapid rate of progression, invasion and recurrence, and 5HT antagonists inhibit the growth of the prostate cancer cell line (PC3).

Materials And Methods: HT1376 (human grade III transitional cell carcinoma) cells were incubated with either 5HT or 5HT antagonists (5HT(1A), 5HT(1B), 5HT(1D), 5HT(2), 5HT(3) and 5HT(4)). After 72 h, cell viability was assessed using the crystal violet assay.

Growth inhibitory effect of doxazosin on prostate and bladder cancer cells. Is the serotonin receptor pathway involved?

Unlabelled: Doxazosin, an alpha1-adrenoceptor antagonist, is used for the treatment of benign prostatic hyperplasia (BPH) and hypertension. Alpha-adrenoceptor antagonists also inhibit growth and induce apoptosis in malignant prostatic cells. The apoptotic activity is independent of their capacity to antagonize alpha-adrenoceptors.

Smooth muscle and purinergic contraction of the human, rabbit, rat, and mouse testicular capsule.

The smooth-muscle cells of the testicular capsule (tunica albuginea) of man, rat, and mouse were examined by electron microscopy. They were characteristically flattened, elongated, branching cells and diffusely incorporated into the collagenous matrix and did not form a compact muscle layer. Contractile and synthetic smooth-muscle cell phenotypes were identified.

The role of serotonin in tumour growth (review).

Serotonin (5-hydroxytryptamine; 5HT) a monoamine neurotransmitter mediates a wide range of physiological actions in the human body. For example 5HT is implicated in psychiatric and neurological disorders and also plays a fundamental role in tumour growth, differentiation and gene expression. 5HT acts as a growth factor for several types of tumoural and non-tumoural cells.

Immunocytochemical and pharmacological characterisation of P2-purinoceptor-mediated cell growth and death in PC-3 hormone refractory prostate cancer cells.

Background: Extracellular nucleotides (e.g adenosine 5'-triphosphate, ATP) influence biological processes via purinergic receptors. We characterised the P2-purinoreceptors in human hormone refractory prostate cancer (HRPC) cells (PC-3 cells).

Erectile dysfunction: a need for greater awareness.

Research has led to effective treatment regimes for erectile dysfunction (ED). Convincing evidence links vascular risk factors (hypertension, diabetes mellitus, hyperlipidaemia and smoking) with ED. This association is not surprising since the corpus cavernosum is a modified vascular tissue.

Direct measurement of hepatic tissue hypoxia by using a novel tcpO2/pCO2 monitoring system in comparison with near-infrared spectroscopy.

Background/aims: Hepatic hypoxia occurs during liver surgery and transplantation and it may also appear within liver tumours, correlating with prognosis and efficacy of the treatment. The present study measured liver tissue hypoxia by directly using near-infrared spectroscopy (NIRS) and a novel tcpO2/pCO2 monitoring system.

Methods: Graded hypoxia was achieved in a rabbit model by a stepwise reduction of the fraction of inspired oxygen (FiO2) from 0.