Biomedical subjects
Publications and source records attributed to Alessandro Palmieri.
Friedel-Crafts reaction of indoles with alpha-amido sulfones in the presence of montmorillonite K-10 leads unexpectedly to 3-(1-arylsulfonylalkyl) indoles in good yield. The obtained products can be further desulfonylated under reductive or alkylative conditions giving linear and branched 3-substituted indoles.
Sphingosine 1-phosphate (S1P) is the natural ligand for a specific G protein-coupled receptors. In endothelial cells, S1P has been shown to modulate the activity of the endothelial nitric-oxide synthase (eNOS) through phosphorylation operated by Akt. Nitric oxide (NO) produced by neuronal nitric-oxide synthase and eNOS plays a central role in triggering and maintaining penile erection. This study has assessed the possibility of a similar cross-talk between eNOS and S1P in human corpus cavernosum and whether this interaction is connected to penile vascular response. Quantitative reverse transcription-polymerase chain reaction demonstrated the presence of S1P(1), S1P(2), and S1P(3) receptors in both the human corpus cavernosum (HCC) and the penile artery. S1P on its own did not relax or contract HCC strips, but on the other hand, incubation with S1P (0.1 microM) caused a 6-fold increase in relaxation induced by a subliminal dose of acetylcholine. This effect is dependent upon eNOS activation through an Akt-dependent phosphorylation, as demonstrated by pharmacological modulation with l-nitroarginine methyl ester and wortmannin and by Western blot studies. In human tissue, S1P seems to be the possible candidate for the activation of the eNOS calcium-independent pathway. This pathway may represent a new therapeutic area of intervention in erectile dysfunction (ED) to develop a way to selectively promote NO production at the endothelial level. This approach could also be used to enhance phosphodiesterase 5 therapy in patients with ED that are poor responders, such as in the case of diabetes.
The reaction of primary 1,3-dinitroalkanes with 2-ene-1,4-dione or 2-ene-4-oxo ester derivatives in acetonitrile with DBU as base, allow the one pot synthesis of 3,5-alkylated acetophenones and methyl benzoate derivatives respectively via an anionic domino process.
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AIM: To evaluate the efficacy, safety, and tolerability of a flexible-dose regimen of vardenafil in a community-based population of men with erectile dysfunction (ED). METHODS: This was a 12-week, open-label, flexible-dose, multicenter study of unselected men with ED of diverse origins and severity. Unlike previous studies, prostatectomy-induced ED and previous unresponsiveness to sildenafil were not exclusion criteria. After 4 weeks of treatment with 10 mg of vardenafil, the dose could be continued or titrated to 5 mg or 20 mg, depending on efficacy and tolerability. After 8 weeks, another dose change was possible. Efficacy was assessed with International Index of Erectile Function erectile function (IIEF-EF) domain scores, diary questions of the Sexual Encounter Profile (SEP), and a global assessment question (GAQ) about erection improvement during the previous 4 weeks. RESULTS: Safety was evaluated in 497 patients, and 480 were suitable for intention-to-treat analysis. After 12 weeks of treatment, the mean per patient rate of successful intercourse, defined by an affirmative response to SEP questions 1-3, was 72%, and was related to age and ED duration. The overall success rate increased from 66% at week 4 to 77% at week 12. The mean IIEF-EF domain score of the whole population increased from 17.2 (baseline) to 24.4 (endpoint). At week 12, the best scores were obtained by patients taking 5 mg and 10 mg. At week 12, GAQ scores showed improved erection in 97.4%, 94.8%, and 78.8% of patients in the 5 mg, 10 mg, and 20 mg group, respectively. Safety was excellent: no serious drug-related event was reported, and only 2.2% of patients discontinued treatment because of side-effects. CONCLUSIONS: Vardenafil was effective and well tolerated in this community-based ED population that is truly representative of the general ED population. Dose titration meets the patient's needs and optimizes clinical outcome.
The Lewis acid promoted allylation of aldehydes has become an important carbon-carbon bond forming reaction in organic chemistry. In this context, we have developed an alternative over existing catalytic processes, wherein aldehydes are subject in acetonitrile to reaction of allylation with allyltributylstannane in the presence of 1.0 equiv of cerium(III) chloride heptahydrate (CeCl(3).7H(2)O), an inexpensive and mild Lewis acid. The allylation has been accelerated by using an inorganic iodide as a cocatalyst, and various iodide salts were examined. The procedure must use allylstannane reagent instead of allylsilane reagent, desirable for environmental reasons, but high chemoselectivity was observed, and this is opposite the results obtained with other classical Lewis acids such as TiCl(4) and Et(2)O.BF(3).
PURPOSE: We used computerized imaging analysis to compare the collagen content of detrusor specimens between patients affected with symptomatic obstructive benign prostatic hyperplasia (BPH) and asymptomatic controls. MATERIALS AND METHODS: In our study we enrolled 36 patients with symptomatic urodynamically obstructed BPH undergoing transurethral resection of the prostate. We also enrolled 28 men (mean age 61.3, range 55 to 70) undergoing transurethral resection of the bladder for primitive, singular Ta bladder cancer, with no significant urinary symptoms, as the control group. During the transurethral surgical procedure in controls and in patients with BPH, a biopsy was performed deep through the muscular layer from either of the lateral bladder walls. Computerized morphometric analysis of the stained sections was performed with an image analysis system, and a percentage of collagen fibers was extracted through morphological filtering and expressed as a mean percentage of the total bioptic area. RESULTS: Collagen content in bladder detrusor specimens was significantly higher in patients with BPH compared to controls (48% and 17% of bioptic area, respectively, p <0.001). Mean detrusor collagen content was clearly higher in patients with severe symptoms than in patients with moderate symptoms (50.45 +/- 8.22% and 43.09% +/- 7.05%, respectively). CONCLUSIONS: Our study supports the important role of detrusor collagen neo-deposition in determining lower urinary tract symptoms in obstructive BPH. Detrusor collagen content correlates with urodynamic obstruction, the presence and severity of symptoms and, given that collagen neoformation is irreversible could probably have a role in the postoperative persistence of lower urinary tract symptoms in patients undergoing surgery for BPH.
The beta(3)-adrenoreceptor plays a major role in lipolysis but the role and distribution of beta(3)-receptors in other specific sites have not been extensively studied. beta(3)-adrenergic receptors are present not only in adipose tissue but also in human gall bladder, colon, prostate, and skeletal muscle. Recently, beta(3)-adrenergic receptor stimulation was shown to elicit vasorelaxation of rat aorta through the NO-cGMP signal transduction pathway. Here we show that beta(3)-receptors are present in human corpus cavernosum and are localized mainly in smooth muscle cells. After activation by a selective beta(3)-adrenergic receptor agonist, BRL 37344, there was a cGMP-dependent but NO-independent vasorelaxation that was selectively blocked by a specific beta(3)-receptor antagonist. In addition, we report that the human corpus cavernosum exhibits basal beta(3)-receptor-mediated vasorelaxant tone and that beta(3)-receptor activity is linked to inhibition of the RhoA/Rho-kinase pathway. These observations indicate that beta(3)-receptors may play a physiological role in mediating penile erection and, therefore, could represent a therapeutic target for treatment of erectile dysfunction.
Erectile dysfunction is a recognized complication of prostate and bladder radical surgery, although there is significant variation in the reported risk, much of this variability is related to the retrospective nature of most previous studies. Undoubtedly, the quality of life of bladder and prostate cancer patients would be much improved if both normal micturition and potency are preserved, which is the subject of this article. Quality of life studies can delineate sexual function after radical prostatectomy, including the use of sexual aids. Penile erection is a neurovascular event modulated by neurotransmitters and hormonal status. The penis is innervated by autonomic and somatic nerves. Both surgery and radiation therapy appear to affect such a mechanism. Radiation is thought to produce Erectile Dysfunction (ED) by accelerating microvascular angiopathy causing cavernosal fibrosis or stenosis of the pelvic arteries and by accelerating existing arteriosclerosis, leading to vascular impotence. Years may elapse before clinically significant ED occurs. Criteria that influence recovery of erections after surgery include younger patient age, stronger erections before operation, preservation of the neurovascular bundles, and attention to fine details in the surgical technique. Recovery of erections occurs in 68% of preoperatively potent men treated with bilateral nerve-sparing surgery and in 47% of those treated with unilateral nerve-sparing surgery.
OBJECTIVES: Peyronie's disease is the most frequent cause of penile curvature and occurs particularly in middle-age patients. The best technique for penile biopsy, in the evaluation of albuginea and cavernous tissue, has not been delineated yet. We present a new technique of penile biopsy, useful in the study of Peyronie's plaque, fibrosis and erectile dysfunction or any other pathological condition of the penis requiring a biopsy. METHODS: A treatment group (A) of 380 patients underwent Extra Shock Waves Treatment (ESWT) three times a week for 20 minutes, followed by a complete cycle of 12 injections of verapamil (10mg), every two weeks for six months. A control group (B) of 92 patients underwent verapamil injections alone. Three months after the end of the treatment, each patient underwent penile biopsy performed with Acu-Punch (Acuderm Inc.), a biopsy-punch armed with a well-sharpened rotating cylindrical blade, first used by dermatologists for cutaneous lesions. RESULTS: A reduction of the plaque volume was found in 260/380 patients (68.4%) of group A and in 28/92 (30.4%) of group B; painful erection weaned off in 312/340 patients of group A (91.7%) and in 36/82 patients (43.9%) of group B. In all 472 patients an excellent specimen was obtained and both the tunica albuginea and the cavernous tissue were easily identified. In the 260 cases, in which the Extra Shock Waves Treatment was successful, scanning and transmission electron microscopy demonstrated a reduction in packing and clumping of the collagen fibers. CONCLUSIONS: This new technique of penile biopsy with Acu-Punch can replace surgical biopsies when a surgical operation is not indicated. Such a low-invasive technique could be performed in all cases of Peyronie's disease and allows a more extensive use of microscopic analysis in the study of Peyronie's disease.