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Biomedical subjects

E Lledó

Publications and source records attributed to E Lledó.

6 recordsLinked to original sources
PubMed2001

The phosphodiesterase inhibitory selectivity and the in vitro and in vivo potency of the new PDE5 inhibitor vardenafil.

We investigated the potency and the selectivity profile of vardenafil on phosphodiesterase (PDEs) enzymes, its ability to modify cGMP metabolism and cause relaxation of penile smooth muscle and its effect on erections in vivo under conditions of exogenous nitric oxide (NO) stimulation. PDE isozymes were extracted and purified from human platelets (PDE5) or bovine sources (PDEs 1, 2, 3, 4 and 6). The inhibition of these PDEs and of human recombinant PDEs by vardenafil was determined. The ability to potentiate NO-mediated relaxation and influence cGMP levels in human corpus cavernosum strips was measured in vitro, and erection-inducing activity was demonstrated in conscious rabbits after oral administration together with intravenous doses of sodium nitroprusside (SNP). The effects of vardenafil were compared with those of the well-recognized PDE5 inhibitor, sildenafil (values for sildenafil in brackets). Vardenafil specifically inhibited the hydrolysis of cGMP by PDE5 with an IC50 of 0.7 nM (6.6 nM). In contrast, the IC50 of vardenafil for PDE1 was 180 nM; for PDE6, 11 nM; for PDE2, PDE3 and PDE4, more than 1000 nM. Relative to PDE5, the ratios of the IC50 for PDE1 were 257 (60), for PDE6 16 (7.4). Vardenafil significantly enhanced the SNP-induced relaxation of human trabecular smooth muscle at 3 nM (10 nM). Vardenafil also significantly potentiated both ACh-induced and transmural electrical stimulation-induced relaxation of trabecular smooth muscle. The minimum concentration of vardenafil that significantly potentiated SNP-induced cGMP accumulation was 3 nM (30 nM). In vivo studies in rabbits showed that orally administered vardenafil dose-dependently potentiated erectile responses to intravenously administered SNP. The minimal effective dose that significantly potentiated erection was 0.1 mg/kg (1 mg/kg). The selectivity for PDE5, the potentiation of NO-induced relaxation and cGMP accumulation in human trabecular smooth muscle and the ability to enhance NO-induced erection in vivo indicate that vardenafil has the appropriate properties to be a potential compound for the treatment of erectile dysfunction. Vardenafil was more potent and selective than sildenafil on its inhibitory activity on PDE5.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

Isolated kidney controlled perfusion with true physiological pulsatile waveform.

A computer controlled perfusion system has been developed to study the behavior of perfused kidneys in several conditions. The system is designed to perform kidney perfusions at constant pressure and low temperature (about 4 degrees C). We compared 2 types of perfusion pumps, a classical roller pump widely used in hemodialysis circuits and a vacuum powered tubular pump with active valves developed by our group and able to produce a flow pattern very similar to the pulse wave in the human circulatory system. In this preliminary study, we show the hydrodynamics obtained with both pumps in isolated hypothermic kidneys perfused with this system. The different flow patterns with both pumps seem to determine differences in the preservation conditions of the kidney.

Animals↗
PubMed1998

Buckling of cylinders may cause prolonged penile pain after prosthesis implantation: a case control study using magnetic resonance imaging of the penis.

PURPOSE: We identify risk factors associated with chronic postoperative penile pain after inflatable prosthesis insertion. MATERIALS AND METHODS: We performed a case control study to determine the incidence of prolonged penile pain in 65 men who underwent prosthesis insertion. The association of various potential risk factors, including diabetes mellitus, incision site, prosthesis type, patient age and history of pelvic surgery, was assessed. In addition, the penis was examined for physical findings, and penile magnetic resonance imaging (MRI) was done as an in situ evaluation of the anatomical position and functional status of the inflatable prosthesis. RESULTS: A total of 14 patients (21.5%) with prolonged pain were compared to the remaining 51 with no pain. All parameters evaluated were similar in both groups except for MRI findings. Of the 14 patients with pain 12 (85.7%) had buckling of the cylinders in the flaccid state compared to only 1 of the 51 controls (1.9%). Statistical analysis showed a highly significant association between buckling and penile pain (odds ratio 300, p <0.0001). Surgical correction of buckling resolved pain in 5 patients. CONCLUSIONS: Prolonged postoperative penile pain after prosthesis insertion is strongly associated with cylinder buckling. This buckling may be the consequence of an excessively long cylinder or an appropriate size cylinder that fails to reach the crural end. The method of accurately diagnosing these alterations is MRI of the penis.

Case-Control Studies↗
PubMed1996

[Chronic prostatitis: diagnostic and therapeutic considerations].

Chronic prostatitis, whether of bacterial or non-bacterial origin, is a pathological entity commonly considered difficult to diagnose and to manage. In an attempt to provide a better understanding of the usefulness of Stamey-Meares fractional culture as a diagnostic test, the findings obtained with this technique in 34 patients, 5 with bacterial chronic prostatitis (BCP) and 29 with non-bacterial chronic prostatitis (NBCP) were analyzed. The multiresistance found in the antibiogram in 3 cases and the lack of correlation between these findings and the seminoculture, demonstrate that this technique should continue to be considered indispensable. Also, the value that should be appointed to the existence of organisms with non-proven pathogenicity is discussed. Some bases for a rational management are proposed and the various treatment alternatives, including the use of myorelaxants which in this series allowed to achieve resolution of the symptomatology in 59% cases are analyzed.

Adult↗
PubMedDate not supplied

[Present and future of kidney transplantation].

Renal transplant is the treatment of choice for the patient with end stage renal disease. Spain is the country with the highest donation rate (33 ppm). However, at present this figure is stabilized. The development of non-beating heart programmes, living-donor nephrectomy (specially laparoscopic nephrectomy) programmes, and may be xenotransplantation in a non-immediate future could increase the transplantation activity. The knowledge of preservation mechanisms, specially with the use of perfusion machines allows to rescue for transplantation kidneys with a long warm-ischemia time. Furthermore, these machines are useful for analyzing viability markers. The new immunosuppressive drugs: Tacrolimus, Mycophenolate-Mophetil, Rapamycin and monoclonal antibodies against alpha chain of the interleukine-2 receptor (Basoliximab and Dazcizumab) have reduced the incidence of acute rejection in the immediate renal transplant period. However, its effect in the long-term follow-up period is still a matter of controversy. The incidence of tumour in the renal transplant recipient is increased, specially those of lymphoma, skin cancer and Kaposi sarcoma. Periodical exams for detecting the development of tumours are mandatory in this population. Finally, xenotransplantation is an attractive alternative, although immunological, infective and ethical barriers should previously be resolved.

Forecasting↗