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Biomedical subjects

Manit Arya

Publications and source records attributed to Manit Arya.

32 records · Page 2Linked to original sources

New phosphodiesterase inhibitors in the treatment of erectile dysfunction.

Sildenafil revolutionised the treatment of erectile dysfunction (ED) on its introduction in 1998. Not only is it effective, but is, perhaps even more importantly, an extremely acceptable manner in which to treat ED (i.e., oral pharmacotherapy), compared to the other treatments that were available at that time (e.g., intracavernosal injection). Whilst sildenafil remains the market leader for ED treatment, it does have some shortcomings: its clinical efficacy is diminished in 'difficult to treat' patient groups, such as diabetics, side effects, such as blue-tinged vision and headache, and the need to time the ingestion of sildenafil to 1 h prior to expected time of sexual intercourse. Recently, newer phosphodiesterase inhibitors ('sons of viagra') have become available, and potentially to improve upon, what has become regarded as the gold standard for ED treatment. This review article discusses the differences between vardenafil, tadalafil and sildenafil, in order to allow the clinician to make an informed decision as to which phosphodiesterase inhibitor to prescribe when dealing with the ever expanding number of patients seeking help for ED.

3',5'-Cyclic-GMP Phosphodiesterases↗

Peyronie's disease: an update of the medical management.

Peyronie's disease (PD) is characterised by penile plaque formation, pain, penile deformity and erectile dysfunction. It is a fibrotic disorder of the tunica albuginea with a poorly understood aetiology and epidemiology. PD may be classified into inflammatory (acute) and chronic stages. Medical treatment is usually instigated during the inflammatory phase of the disease. A review of the literature reveals a wide range of oral, intralesional and alternative therapies that are discussed in relation to established pathophysiological mechanisms of the disease. The advantages and disadvantages of each treatment are summarised. This review also discusses the ongoing therapeutic dilemmas of PD and suggests a treatment strategy based on an analysis of the urological literature.

Humans↗

Alternative use of botulinum toxin in urology.

Botulinum toxin A is used in the treatment of lower urinary tract symptoms due to detrusor sphincter dysynergia and detrusor hyper-reflexia (neurogenic detrusor deficiency). The toxin acts by producing paralysis of muscle tissue and has been shown to be safe and effective in the treatment of conditions caused by increased muscle tonicity and spasticity. Here the literature is reviewed chronologically, the established and emerging indications for the urological use of botulinum toxin evaluated and future applications are also considered.

Botulinum Toxins↗

The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis.

AIM: Chemokines or chemotactic cytokines are known to be important in the directional migration or chemotaxis of leucocytes in conditions of homeostasis and in inflammatory or immunological responses. However, the role of chemokines is extending beyond their involvement in mediating leucocyte trafficking with an increasing body of evidence suggesting these proteins are intimately involved in many stages of tumour development and progression. Our aim was to study the role of the CXCL12:CXCR4 chemokine ligand:receptor complex in determining the organ-specific metastasis of prostate cancer. MATERIALS AND METHODS: CXCR4 mRNA expression was determined by RT-PCR in 3 metastatic prostate cancer cell lines DU145, LNCaP and PC3, the primary prostate cancer cell line 1542 CPT3X and the normal prostate epithelial cell lines 1542 NPTX and Pre 2.8. This was followed by Taqman quantitative PCR analysis of CXCR4 mRNA in these cell lines. Flow cytometry analysis was then used to measure the expression of the CXCR4 receptor protein on the cell surface. The influence of the receptor on cell migration was studied using Transwell, Migration Assays. Finally, Taqman quantitative PCR was performed on RNA obtained from laser microdissected fresh primary prostate tumour and benign tissue samples from patients. RESULTS: In DU145, LNCaP and PC3 CXCR4 mRNA expression was approximately 1000, 400 and 21 times respectively that of 1542 NPTX, Pre 2.8 and 1542 CPT3X. In patient primary tumour samples and patient benign tissue specimens CXCR4 mRNA expression was similar to that of the metastatic cell line DU145. Flow cytometry analysis showed that significantly higher levels of the CXCR4 receptor were present on the cell surface of the 3 metastatic cell lines. Migration studies revealed that chemotaxis of the metastatic cell lines PC3 and DU145 was enhanced by CXCL12 ligand and inhibited by antibody to CXCR4. CXCL12 did not influence the migration of the normal prostate epithelial cell line 1542 NPTX. CONCLUSIONS: We have demonstrated that human prostate cell lines derived from metastases express functional CXCR4 receptor and that CXCL12 ligand enhances their migratory capabilities. Also, laser microdissected primary patient tumours and patient benign tissue specimens express CXCR4 mRNA at high levels (it is suggested that post-transcriptional modification of the CXCR4 receptor plays a major role in regulating protein expression). These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.

Cell Line, Tumor↗

Bladder cancer: a current update.

In the UK, 10,000 new cases of bladder cancer are reported per annum. Earlier diagnosis and better care have improved survival rates, but the incidence is still rising. This article updates the current understanding of bladder cancer diagnosis and management.

Algorithms↗

Priapism--a review of the medical management.

Priapism is characterised by the presence of prolonged, often painful penile erection in the absence of a sexual stimulus. This rare condition has a range of aetiologies, but is most common following self-administration of injection therapy for impotence. Priapism may be classified into high- and low-flow states. Low-flow priapism is an emergency ischaemic condition requiring prompt recognition and treatment to avoid devastating long-term complications of erectile dysfunction. Wide-ranging medical therapies are covered in this review. Diagnostic and treatment algorithms are suggested in light of the current available literature.

Humans↗

Testicular cancer: current update and controversies.

Testicular cancer is an important disease affecting young men. The overall 5-year survival has improved to 95%. The goal now is to maintain the efficacy of treatment in advanced disease while reducing the associated side effects.

Algorithms↗

Benign prostatic hyperplasia: solutions to an ageing problem.

As the population ages, the demand for treatment of the symptoms of benign prostatic hyperplasia has never been higher. Equally the choice of treatments has never been greater. This review considers the medical and surgical options.

Adrenergic alpha-Antagonists↗

Luteinising hormone releasing hormone analogues in the treatment of prostate cancer.

The use of the luteinising hormone releasing hormone (LHRH) analogues--goserelin (Zoladex, AstraZeneca) and leuprorelin (Prostap, Wyeth)--is well established and forms the backbone of the treatment of locally advanced and metastatic prostate cancer. Comparable efficacy with orchidectomy and, historically, diethylstilbestrol (DES) is accepted, with the advantages of reversibility and limited thromboembolic and cardiovascular toxicity, respectively. Side effects such as hot flushes, loss of libido, lethargy and decreased bone mineral density have recently stimulated more interest in the use of non-steroidal anti-androgens such as bicalutamide (Casodex, AstraZeneca) in locally advanced disease. Although better tolerated, bicalutamide has significant problems with gynaecomastia and breast pain. Maximal androgen blockade using LHRH analogues and their adjuvant use with radiotherapy are discussed, as well as their experimental application in intermittent androgen suppression therapy. Similar side effect profiles are reported for the LHRH analogues but injection tolerability differs with the smaller 23G needle for Prostap 3 compared to the 16G needle for Zoladex LA. There is no evidence to suggest a difference in the efficacy between the LHRH analogues goserelin and leuprorelin, although no direct comparison has yet been undertaken.

Androgen Antagonists↗

Current concepts in the pharmacotherapy of benign prostatic hyperplasia.

Benign prostatic hyperplasia is a major men's health issue, with approximately 80% of all men developing this condition within their lifetime. A variety of oral treatments is available, including alpha-adrenoceptor antagonists (alpha-blockers), 5alpha reductase inhibitors, aromatase inhibitors and phytotherapy. A large number of alpha-blockers can be administered, but no single agent has demonstrated a clear superiority over the other drugs. 5alpha Reductase inhibitors have demonstrated similar efficacy in larger volume prostates but most evidence suggests that there is no benefit in combining them with alpha-blockers. The use of phytotherapy is not entirely novel but requires further long-term evaluation before it can be endorsed for clinical use in benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗