Decorin as a new treatment alternative in Peyronie's disease: preliminary results in the rat model.

The purpose of this study is to investigate the effect of decorin, a naturally occurring proteoglycan with anti-transforming growth factor beta (TGF-ß) activity, on the rat model of Peyronie's disease (PD). Twenty-five adult male Sprague-Dawley rats were divided in three groups: I) TGF-ß (0.5 µg) injected (n: 8); II) TGF-ß injected and decorin treated (n: 8); and III) controls (n: 9). Decorin (0.5 µg per day) was given with intracavernous injection on the second, third, fourth and fifth day following TGF-ß injection. All rats underwent electrical stimulation of the cavernous nerve after 6 weeks. Intracavernosal and arterial blood pressures were measured during this procedure. Cross-sections of the rat penises were examined using Mason trichrome and H&E stains. Statistical analyses were carried out using one-way anova. Histopathological examinations confirmed the Peyronie's-like condition in TGF-ß-injected rats, which exhibited a thickening of the tunica albuginea (TA), when compared to controls. Disorganisation of collagen on the TA was also prominent in TGF-ß-injected rats, but not in decorin-treated and control rats. Decorin-treated rats showed significantly higher maximal intracavernosal pressure (MIP) responses to cavernous nerve stimulation, when compared to group 1 (P < 0.05). Our results indicate that decorin antagonises the effects of TGF-ß in the rat model of PD and prevents diminished erectile response to cavernous nerve stimulation.

TGF-beta1 neutralizing antibodies decrease the fibrotic effects of ischemic priapism.

The objective of this study was to evaluate the possible role of transforming growth factor beta 1 (TGF-beta1) antibodies (ab) for the prevention of fibrotic effects of priapism in a rat model. In total, 30 adult Sprague-Dawley rats were divided into five groups. Priapism with 6 h (group 1), priapism with 6 h+ab (group 2), priapism with 24 h (group 3), priapism with 24 h+ab (group 4) and control (group 5). Priapism was induced with a vacuum erection device and a rubber band was placed at the base of the erect penis. At 1 h after the initiation of priapism, TGF-beta1 antibodies were given intracavernosaly. All rats underwent electrical stimulation of the cavernous nerve after 8 weeks. Intracavernous and systemic blood pressures were measured during the procedure. Rats in group 1 showed significantly higher (intracavernosal pressure (ICP) pressures to cavernous nerve stimulation and had higher ICP/BP ratios when compared to other groups. Similarly, histopathologic examination revealed less fibrosis in group 2, compared with the other groups. Consequently, TGF-beta1 antibodies antagonise the fibrotic effects of TGF-beta1, especially in cases with duration of priapism less than 6 h.

The effects of different 4-aminopyridine and morphine combinations on the intensity of morphine abstinence.

The glutamatergic system is deeply involved in the development of opiate dependence and in the manifestation of opiate abstinence syndrome. In this study the effect of the increase in the endogenous glutamate (GLU) release due to 4-aminopyridine (4-AP), a potassium channel blocker, during the development of morphine (M) physical dependence and during the naloxone (NL)-precipitated abstinence syndrome was investigated. For the development of physical dependence M was intraperitoneally (i.p.) injected for 9 days 105 min following i.p. saline administration to a group of rats. In the first 3 days the dose of M was 10 mg x kg(-1). In the second 3 days the initial dose was doubled (20 mg x kg(-1)) and in the last 3 days the dose of M was raised to 40 mg x kg(-1). On day 10, the rats were divided into three groups at random and these three groups were i.p. given saline 105 min before 80 mg x kg(-1)M, 2 mg x kg(-1) 4-AP 105 min after 80 mg x kg(-1) M, and 80 mg x kg(-1) M 105 min before 2 mg x kg(-1) 4-AP, respectively. In a second group of rats, the rats were i.p. given 2 mg x kg(-1) 4-AP 105 min prior to M administration, which was increased every 3 days (10 mg x kg(-1), 20 mg x kg(-1), 40 mg x kg(-1)). On day 10, the rats were divided into two groups whose first injection was saline and 2 mg x kg(-1) 4-AP, respectively. The second injections of both groups after an interval of 105 min following the first one contained 80 mg x kg(-1) M. In contrast, one group of rats received only i.p. saline at every other injection time (the control group). Furthermore, another group of rats was i.p. administered 2 mg x kg(-1) 4-AP once a day, as the first injection. At the second injection time they were i.p. given saline. After a period of 15 min following the last administration on day 10, the rats belonging to all groups were i.p. injected with 2 mg x kg(-1) NL and immediately placed in a metal cage. Body weight loss (g), teeth chattering, rearing, wet-dog shaking, grooming, and jumping were determined or counted for 15 min. Penile erection, defecation, and diarrhoea were separately scored with one point for every individual occurrence, and the total score was named 'total number of others'. The administration of 4-AP before M appeared to intensify the development of dependence, and was most probably due to the Ca2+-induced inactivation of NMDA receptors as a result of excess release of GLU when the 4-AP took effect. The inactivation of NMDA receptors should have acted as a transient blockade of the receptors during the chronic administration period, and as well as after a single administration on day 10 before M injection and before abstinence. The intensification of the abstinence syndrome may be dependent on the excessive GLU released by 4-AP.