G. Mirabella

Differential gene expression of cholinergic muscarinic receptor subtypes in male and female normal human urinary bladder

OBJECTIVES To study the mRNA expression of each muscarinic receptor subtype in bladder areas involved in micturition, such as the bladder dome, neck, and trigone. Our study focused on the analysis of the gene expression of muscarinic receptors in the human male and female urinary bladder. Other than the well-known role of bladder parasympathetic innervation, an extensive study of the muscarinic receptor mRNA distribution in male and female urinary bladder is still lacking. METHODS The study was carried out on 5 female (age 56 +/- 10 years) and 5 male (age 70 +/- 9 years) patients. The patients selected for this study did not have any lower urinary tract symptoms, as determined by International Prostate Symptom Score questionnaire. The mRNAs encoding muscarinic receptor subtypes were assessed by reverse transcription-polymerase chain reaction, followed by Southern blot analysis. RESULTS Using a molecular approach, we demonstrated the presence of all muscarinic receptor subtypes in the different urinary bladder areas involved in micturition; in particular, our data indicated that mRNAs encoding muscarinic receptors are largely expressed in all examined bladder areas, both in men and women, although with some remarkable differences and a peculiar distribution. CONCLUSIONS Our results indicate that the pharmacology of the human bladder may be more complex than previously recognized. Furthermore, the choice to study each biopsy as a single sample and not use a pool of tissues allowed us to point out the individual variability between subjects and sex-related differences in the expression profile of muscarinic receptor subtype mRNAs.

Hydronephrosis caused by inferior vena cava penetration by a mobin-uddin filter

The inferior vena cava (IVC) filter placement represents an excellent protection from significant pulmonary embolism in at-risk patients. Perforation of the wall of the IVC by components of caval filters is a recognized complication. We report a case of asymptomatic hydronephrosis caused by transcaval penetration of a Mobin-Uddin filter.

Alpha1 Adrenoceptor Subtypes in Human Urinary Bladder: Sex and Regional Comparison

The aim of this work is to report a detailed study of the presence of α1 AR subtypes in human urinary bladder areas involved in the micturition (i.e. detrusor, trigone and neck), investigating whether or not there are differences between sexes. Methods Urinary bladder specimens were obtained as discarded tissue after cystectomy for vesical carcinoma (17 men and 14 women). Molecular characterization of α1 AR subtypes was done by semi-quantitative RT-PCR. The α1 AR protein expression was studied by saturation binding curves using the α1 AR antagonist 125I-HEAT and by western blot. Analysis of data was performed using the GraphPad PRISM 4 software. Results Results obtained indicated that α1 AR proteins were detectable in each bladder area. In both sexes, the detrusor and the neck expressed similar levels of α1 ARs: respectively, detrusor: 14.6 ± 1.2 in men and 13.1 ± 1.1 fmol/mg prot in women; neck: 16.9±3.2 in men and 17.5 ± 4.1 fmol/mg prot in women. In the trigone, significantly higher α1 ARs were found in women compared to men (20.6 ± 1.1 vs 11.7 ± 0.7 fmol/mg prot). Subtype analysis indicated that in women, each area was endowed with mRNA and protein encoding for each α1 AR subtype. The men detrusor expressed α1A and α1D ARs, while in the trigone and the neck, each subtype was present. Conclusions A selective distribution of α1 ARs did exist between sexes and between the different areas involved in micturition, supporting evidence which indicates a role of different α1 AR subtypes in the pathophysiology of the lower urinary tract symptoms.

Evidence for the Presence of α1 Adrenoceptor Subtypes in the Human Ureter

Several studies proposed a role for α1 adrenoceptors (α1 ARs) in the ureteral physiology, indicating that they are present in the ureter; however, few studies have been made to identify α1 AR subtypes present in this area. Thus, this study was carried out to characterize the α1 AR subtype gene and protein expression in proximal, medial and distal region of the human ureter. Methods Molecular characterization of α1 AR subtypes was done by semi-quantitative RT-PCR. The α1 AR protein expression was studied by saturation binding curves using the α1 AR antagonist 125I-HEAT. Analysis of data was performed using the GraphPad PRISM 4 software. Results Analysis of saturation binding curves revealed an heterogeneous distribution of α1 AR binding sites; the Bmax for the distal ureter was indeed 52.5 ±5.4 fmol/mg prot, while a lower similar density of α1 ARs was demonstrated in the medial (25.2 ±1.7 fmol/mg prot) and proximal (23.4 ±0.4 fmol/mg prot) ureters. Molecular characterization of α1 AR subtypes indicated that each receptor was present, although with differences in term of the amount expressed. Conclusions Human ureter was endowed with each α1 AR subtype, although α1D and α1A ARs were prevalent over α1B ARs. Radioligand binding results revealed that there were no significant differences in the Kd between ureteral regions, while an heterogeneous distribution of α1 AR binding sites was detected, with the highest density of α1 ARs in the distal ureter and a lower similar density in the medial and proximal ureter.

Focus on 5 Years of the Acceptance and Adhesion to Prostaglandin El Auto-Intracavernosal Injection in Patients with Erectile Disfunction

From 5/98 to 5/03, of the 1310 patients taking a medical therapy for erectile dysfunction (E.D.), only 137 took autointracavernosal injection (auto. ICI). 134 patients were contacted by phone and were asked to answer a definite questionnaire. Results 49 patients (36.5%) still perform auto-ICI therapy while 85 (63.5%) had given up. 53% of the patients still using auto-ICI make the injection 4, or more times a month, with an erection lasting a considerable time (30–60 minutes). Nobody referred the presence of corpora cavernosa fibrosis. The reasons put forward by patients who stopped the therapy were: a perception of ineffectiveness, therapy rejection, fear of injections and the appearance of intolerable side effects. Conclusions Auto-ICI therapy remains a valid option for patients with E.D. not responding to oral therapy but it needs greater involvement by the physician in order to evaluate the patients psychological discomfort and reduce or eliminate intolerable side effects.