Robert C. Calvert

Smooth Muscle and Purinergic Contraction of the Human, Rabbit, Rat, and Mouse Testicular Capsule

Abstract 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. Nerve varicosities in close apposition to smooth muscle were seen in human tissue. Contractions induced by adenosine 5′-triphosphate (ATP), alpha, beta-methylene ATP, noradrenaline (NA), acetylcholine (ACh), and electrical field stimulation (EFS) of autonomic nerves were investigated. Nerve-mediated responses of the rabbit and human tunica albuginea were recorded. The EFS-induced human responses were completely abolished by prazosin. In the rabbit, EFS-induced contractile responses were reduced by pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid by 36% and by prazosin by 77%. Both antagonists together almost completely abolished all EFS-induced contractions. The human tunica albuginea was contracted by NA, ATP, and alpha, beta-methylene ATP, but not by ACh. The rabbit and rat tunica albuginea were contracted by NA, ATP, alpha, beta-methylene ATP, and ACh. The mouse tunica albuginea was contracted by ACh, ATP, and alpha, beta-methylene ATP, but relaxed to NA. Immunohistochemical studies showed that P2X1 (also known as P2RX1) and P2X2 (also known as P2RX2) receptors were expressed on the smooth muscle of the rodent testicular capsule, expression being less pronounced in man. The testicular capsule of the rat, mouse, rabbit, and man all contain contractile smooth muscle. ATP, released as a cotransmitter from sympathetic nerves, can stimulate the contraction of rabbit smooth muscle. Human, rat, and mouse testicular smooth muscle demonstrated purinergic responsiveness, probably mediated through the P2X1 and/or P2X2 receptors.

Alterations in purinergic and cholinergic components of contractile responses of isolated detrusor contraction in a rat model of partial bladder outlet obstruction

To study the effect of 3 weeks of partial bladder outlet obstruction (BOO), compared to a sham operation, on the cholinergic and purinergic components of detrusor contractile responses to agonists and to electrical field stimulation (EFS); the expression of P2X receptor subtypes was also examined.

Multi‐length or 24 cm ureteric stent? A multicentre randomised comparison of stent‐related symptoms using a validated questionnaire

One of the suggested factors for stent‐related symptoms is that excess distal intravesical stent mass may cause bladder irritation. There is a lack of studies investigating this in a randomised controlled fashion using a validated questionnaire. This study compared two of the most commonly used length of stents (a 30 cm multi‐length vs a 24 cm long stent) and showed no significance difference in stent‐related symptoms in patients with either of these stents.

Changing P2X receptor localization on maturing sperm in the epididymides of mice, hamsters, rats, and humans: a preliminary study

OBJECTIVE To study using immunohistochemistry the localization of P2X receptor subtypes on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. DESIGN Basic research. SETTING University-based hospital. PATIENT(S) Three human epididymides were obtained from patients undergoing orchidectomy for metastatic prostate cancer. MAIN OUTCOME MEASURE(S) P2X(1), P2X(2), P2X(3), and P2X(4) receptor immunolocalization on sperm. RESULT(S) In the present study, P2X(1,2, and 3) receptor localization was immunohistochemically demonstrated on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. P2X(4) receptor immunostaining was also observed on the head of sperm in the caput epididymidis of mice, hamsters, and humans, but not rats. There was a subsequent loss of receptor staining on sperm in the cauda epididymidis, except in humans where staining of P2X(4) receptors persisted. Comparision with peanut agglutinin (PNA) binding studies suggested the P2X receptors were located on the acrosome membrane. P2X(5-7) receptors were examined but found to be absent. CONCLUSION(S) The change in localization of receptor subtypes is coincidental with the functionally essential morphologic and maturational changes seen in sperm as they travel through the epididymis, and is suggestive of a role for purinergic signaling in sperm maturation and possibly fertility.

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

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).

Reduction of endothelin-1 binding and inhibition of endothelin-1-mediated detrusor contraction by naftidrofuryl.

Endothelin-1 (ET-1) causes urinary bladder smooth muscle contraction and the endothelin receptors A and B (ET(A) and ET(B)) are both known to be present in the rabbit urinary bladder. Alterations in ET-1 signalling have been implicated in the pathophysiology of urinary tract disorders secondary to bladder outlet obstruction and also in diabetic cystopathy. Naftidrofuryl (Naf) (marketed under the trade name Praxilene) improves walking distance in patients with peripheral vascular disease, an effect which may be partially attributed to ET-1 antagonism. The purpose of this study is to assess whether Naf will reduce ET-1 binding in the rabbit detrusor muscle and to assess whether there is inhibition of ET-1-mediated detrusor contraction. Detrusor smooth muscle strips were mounted in organ baths and cumulative response curves were measured for ET-1-mediated contractions in the presence and absence of 10(-6) M Naf (therapeutic concentration). In addition, ET-1 was added to the detrusor strips in the presence of the ET(A) antagonist, BQ123, and the ET(B) antagonist, BQ788, to identify the receptor subtype functionally involved. Overall inhibition of [(125)I]ET-1 binding by Naf was assessed using autoradiography. Identification of receptor-subtype binding reduction was assessed using the radioligands [(125)I]PD151242 and [(125)I]BQ3020. Naf inhibited ET-1-mediated detrusor contractions significantly (P<0.04), e.g. at 10(-10) M ET-1, contraction was completely abolished by Naf. Autoradiography indicated that Naf competitively inhibited [(125)I]ET-1 binding in a dose-dependent manner (IC(50)=3x10(-7) M). All radioligand binding was reduced indicating binding of Naf to both ET(A) and ET(B) receptors. Naf reduces binding of ET-1 to rabbit detrusor ET(A) and ET(B) receptors and inhibits ET-1-induced detrusor contractions mediated by ET(A) receptors. Naf may have therapeutic potential in the treatment of bladder disorders secondary to bladder outlet obstruction and diabetes mellitus.

MANAGEMENT OF SEVERE BLUNT RENAL TRAUMA IN ADULT PATIENTS: A 10-YEAR RETROSPECTIVE REVIEW FROM AN EMERGENCY HOSPITAL

Sir, Aragona et al . [ 1 ] report the trend towards successful conservative management of high-grade renal injury witnessed elsewhere [ 2 ] . Over the 5-year period from 2006 to 2010, only one patient with American Association for the Surgery of Trauma (AAST) grade III or IV blunt renal trauma required open surgery in their level I trauma centre. Nevertheless, emergency nephrectomy remains a life-saving treatment for unstable grade V renal injuries. From 2004 to 2008, there were only 62 nephrectomies performed for renal trauma in England [ 3 ] . This is a slight reduction compared with the previous 5-year period (1999 – 2003), when there were 71 cases. This small and reducing number of cases ultimately means that most urologists are lacking regular exposure to such emergency procedures. Additionally, the laparoscopic approach for elective nephrectomy is now the established procedure for most benign and malignant cases, and intradepartmental subspecialisation has resulted in many urologists being on-call who do not regularly perform open nephrectomies. Furthermore, a recent study has highlighted a signifi cant decline in the number of open radical nephrectomies performed by UK urological trainees [ 4 ] .

Book reviews : Clinical drawings for your patients: erectile dysfunction. By Christine M Evans and Philip Kell. Published by Health Press, London 2000. Paperback 70 pp. Price £12.00 ISBN 1-899541-11-X

The sexual male: problems and solutions By Richard Milsten and Julian Slowinski. Published by W W Norton and Company Ltd, London 2000. Paperback 331 pp. Price &pound;10.95 ISBN 0-393-32127-4 This is a well-written book and I have enjoyed reading it. The book is easy to read and understand. Although it deals with a serious matter, the reader is encouraged to have a sense of humour. There is paucity of education about human sexuality in the medical school curriculum. It is therefore little wonder that