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Biomedical subjects

L Nunes

Publications and source records attributed to L Nunes.

At least 19 recordsLinked to original sources
PubMed1998

Histological and ultrastructural alterations in an animal model of Peyronie's disease.

OBJECTIVE: To determine the role of transforming growth factor beta (TGF-beta), one of the cytokines known to induce tissue fibrosis, in the induction of a Peyronie's-like condition, and to produce an animal model for the further study of Peyronie's disease. MATERIALS AND METHODS: Twenty-four adult male Sprague-Dawley rats were divided into two groups: in group 1, different concentrations of cytomodulin, a synthetic heptapeptide with TGF-beta-like activity, were injected into the tunica of each of 18 rats and six rats group 2 received saline injections as a control. The tunical tissues were taken after 3 days, 2 and 6 weeks and were examined histologically using Hart and trichrome stains. Electron microscopy was used to examine the ultrastructural changes in the same tissue samples. RESULTS: There were histological and ultrastructural alterations in 15 of 18 rats in group 1 (cytomodulin-injected), especially in tissue examined after 6 weeks. The most prominent histological changes were chronic inflammatory cellular infiltration, focal and diffuse elastosis, thickening, disorganization and clumping of the collagen bundles. The ultrastructural changes were in the form of densely packed collagen, fragmented and scarce elastic fibres, separation of neuronal fibres by interposing clumps of packed collagen, and perivascular collagen deposition as a part of the reorganization of the interstitial matrix. CONCLUSION: Cytomodulin can induce a Peyronie's-like condition in the rat penis, which may explain the role of TGF-beta in the pathogenesis of Peyronie's disease. With further refinement, such rats may be used as an experimental model for studies of Peyronie's disease.

Animals↗
PubMed1997

Free ureteral replacement in rats: regeneration of ureteral wall components in the acellular matrix graft.

OBJECTIVES: To evaluate ureteral replacement by a free homologous graft of acellular matrix in a rat model. METHODS: In 30 male Sprague-Dawley rats, a 0.3 to 0.8-cm midsegment of the left ureter was resected and replaced with an acellular matrix graft of equal length placed on a polyethylene stent. The animals were killed at varying intervals, and the grafted specimens were prepared for light and electron microscopy. RESULTS: In all animals, the acellular matrix graft remained in its original position without evidence of incrustation or infection, and histologic examination showed complete epithelialization and progressive infiltration by vessels. At 10 weeks, smooth muscle fibers were observed; at 12 weeks, nerve fibers were first detected; at 4 months, smooth muscle cells had assumed regular configuration. CONCLUSIONS: The ureteral acellular matrix graft appears to promote the regeneration of all ureteral wall components.

Animals↗
PubMed1997

Structural alterations in the tunica albuginea of the penis: impact of Peyronie's disease, ageing and impotence.

OBJECTIVE: To investigate whether changes in the structure of the tunica albuginea influence the development of erectile dysfunction. PATIENTS AND METHODS: Biopsy specimens taken from the tunica of 64 patients (both potent and impotent) with and without Peyronie's disease were evaluated. Tissue samples were stained and examined under light and electron microscopy, and the concentration of elastic fibres present in each was measured using computerized image analysis. RESULTS: The concentration of elastic fibres was lower in impotent than in potent patients (P = 0.0365) and was also significantly less in patients with Peyronie's disease. Furthermore, the concentration of elastic fibres decreased with age. Electron and light microscopy revealed the presence of distinct alterations in the tunica albuginea in impotent patients and patients with Peyronie's disease that might interfere with function. CONCLUSION: The decrease in elastic fibre concentration and changes in microscopic features may contribute to erectile dysfunction by impairing the veno-occlusive function of the tunica albuginea.

Adolescent↗
PubMed1997

The anatomy of the tunica albuginea in the normal penis and Peyronie's disease.

PURPOSE: We studied the fine architecture of the tunica albuginea of the penis. MATERIALS AND METHODS: The study included 6 human male cadavers and 10 surgical patients (5 with Peyronie's disease and 5 with normal penile anatomy). RESULTS: The tunica albuginea of the corpora cavernosa is a bi-layered structure with multiple sub layers. Inner layer bundles support and contain the cavernous tissue and are oriented circularly. Radiating from this layer are intracavernous pillars acting as struts, which augment the septum and provide essential support to the erectile tissue. Outer layer bundles are oriented longitudinally. These fibers extend from the glans penis to the proximal crura, where they insert into the inferior pubic ramus. There are no outer layer fibers between the 5 and 7 o'clock positions. Elastic fibers normally form an irregularly latticed network on which collagen fibers rest. In Peyronie's disease the well ordered appearance of the collagen layers is lost: excessive deposits of collagen, disordered elastic fibers and fibrin are found within the region of the plaque. CONCLUSIONS: The normal 3-dimensional structure of the tunica affords great flexibility, rigidity and tissue strength to the penis, which are lost consequent to structural changes in Peyronie's disease.

Humans↗
PubMed1997

Age decreases nitric oxide synthase-containing nerve fibers in the rat penis.

PURPOSE: To study the effect of aging on erectile function in a rat model. MATERIALS AND METHODS: We investigated: 1) the number and distribution of nerve fibers within the corpus cavernosum and dorsal nerve containing vasoactive intestinal polypeptide (VIP) and nitric oxide synthase (NOS); and 2) the erectile response to apomorphine (a central dopamine receptor agonist), electrostimulation of the cavernous nerve, and intracorporeal papaverine injection. RESULTS: The number of NOS-containing nerve fibers was significantly less in the old rats (24 months) than in the young (2.5 months) and intermediate (8.5 months)-aged (63.3 +/- 3.35 vs. 135.1 +/- 10.88 [p < or = 0.0002] and 127.8 +/- 11.65 [p < or = 0.0002]). The number of erections induced by apomorphine was significantly less in the old rats than in the young (1.0 +/- 3.1 vs. 3.6 +/- 0.26; p < 0.002). With electrostimulation, the latency period before the onset of the intracavernous pressure rise was noted to increase with age (2.3 +/- 0.24 sec. for the young vs. 6.77 +/- 0.98 sec. for the old, p < or = 0.0001). The maximal intracavernous pressure after intracavernous papaverine injection decreased with age. CONCLUSION: The erectile mechanism appears to remain intact as rats age, but the response to central and peripheral stimulation decreases. The reduction in NOS-containing nerve fibers might account for these observations.

Aging↗
PubMed1997

[Prevalence of several cardiovascular risk factors in a population in the municipality of Viseu].

STUDY OBJECTIVE: To assess the prevalence of the main changeable cardiovascular risk factors (hypertension, hypercholesterolemia and smoking) in the population of the Viseu municipality. MATERIAL AND METHODS: The population was obtained through a publicity campaign in local radios and on lighted placards in the town of Viseu. We chose a set of volunteers above 20 years of age, who answered a questionnaire about smoking habits, academic qualifications, profession and residence. After the inquiry, the total cholesterol and blood pressure were determined. We considered hypertension (HBP) values > or = 140/90 mmHg and hypercholesterolemia > 200 mg/dl. RESULTS: 1852 persons were inquired (3.2% of the population of the Viseu municipality) 1173 of which were females. According to the age groups, we verified that the ages between 50 and 69 years represented 47.9% of the total amount of volunteers. In what concerns smoking habits, we found a prevalence of 9.1% (15.9% in males and 5.2% in females). In the study of the prevalence of HBP we found a value of 38.5%, higher in males (42.8%) than in females (35.9%). The prevalence of hypercholesterolemia found was 34.9% (no significant differences between the sexes). CONCLUSION: In comparison with other studies carried out in the Portuguese population, a low prevalence of smoking habits, high hypertension and similar hypercholesterolemia were found.

Adult↗
PubMed1995

Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation.

Prazosin (an alpha-1-adrenergic blocker) and cromakalim (potassium channel opener), given alone, induced significant fatigue of the urethral sphincter at a concentration of 10(-4) M; both drugs combined achieved a significant sphincteric fatigue at a concentration of 10(-5) M each. To 10(-4) M hexamethonium (ganglionic smooth muscle blocker) and 10(-4) M decamethonium (nicotinic blocker of striated muscle) the striated urethral sphincter responded like striated muscle with no detectable function of its smooth muscle component. Therefore, the striated component seems to play a dominant role in sphincteric function. With calcium depletion or in the presence of a calcium channel blocker (10(-4) M nifedipine) the urethral sphincter showed a relative enhancement of response to electrical field stimulation when compared with smooth and skeletal muscle, whose responses were both significantly reduced. This phenomenon could not be explained with calcium-dependent, inhibitory, nitric oxide-releasing nerves, as the NO-synthase blocker N-nitro-L-arginine (10(-5) M to 5 x 10(-5) M) failed to induce the enhancement of sphincter contraction during electrostimulation found with calcium depletion. Still, NO-releasing nerves might play a role in sphincteric relaxation because sodium nitroprusside (10(-5) M) induced a significant relaxation of the urethral sphincter precontracted with 80 mM potassium. The potential to weaken sphincteric closure with drugs, exemplified by the results obtained in response to prazosin and cromakalim, would represent a therapeutic advance in the patient with neurogenic bladder dysfunction.

Amino Acid Oxidoreductases↗
PubMed1995

Radiation-induced decrease in nitric oxide synthase--containing nerves in the rat penis.

PURPOSE: Evaluate effect of prostatic irradiation on erectile function. MATERIALS AND METHODS: Forty-seven male adult rats were divided into three groups according to a single radiation dose to the prostate: control (no irradiation) (n = 15), 1,000 cGy (n = 15), and 2,000 cGy (n = 17). Five months after irradiation, rats underwent evaluation of penile vascularity and of erectile response to central and peripheral stimulation. After the study a proximal-shaft penile segment was obtained for staining. RESULTS: Histologic evaluation demonstrated that, with increasing radiation, the number of nitric oxide synthase-containing nerve fibers per penile segment decreased significantly: control, 225.6 +/- 9.7; 1,000 cGy, 156.3 +/- 12.0; 2,000 cGy, 85.8 +/- 10.1 (standard error of the mean). Maximal intracavernous pressure induced with electrostimulation decreased significantly with increasing radiation dose. After injection of papaverine, maximal intracavernous pressure was significantly decreased in only the 2,000-cGy group. CONCLUSION: A dose of 2,000 cGy over the prostatic bed induces erectile dysfunction by causing defects in the vascular supply of the erectile tissue and in the nerves and smooth muscle.

Amino Acid Oxidoreductases↗
PubMed1995

Reinnervation of the rat bladder with a somatic nerve and a striated muscle flap.

PURPOSE: Current techniques of ventral sacral root stimulation to regain voluntary motor control of the decentralized urinary bladder depend upon intact parasympathetic innervation of the detrusor. We investigated techniques that might allow restoration of motor control of the bladder after efferent parasympathetic impairment. MATERIALS AND METHODS: In a chronic rat model, we evaluated whether motor control of a peripherally denervated bladder could be restored by transplantation of autologous excitable tissues and subsequent electrostimulation. Either a somatic nerve or a striated muscle flap was used as the transplant. RESULTS: Four months after the initial surgery, electrostimulation of the somatic nerve implant provoked bladder contractions--a response that was blocked by atropine. Stimulation of the nerve innervating the striated muscle flap also provoked bladder contractions; these were not affected by atropine and were slightly reduced by hexamethonium. CONCLUSION: Reinnervation of the bladder with somatic nerves or striated muscles is possible in principle. Future experiments will clarify the clinical significance of electrostimulation of such implants.

Animals↗
PubMed1995

Regeneration of nitric oxide synthase-containing nerves after cavernous nerve neurotomy in the rat.

In patients who recover erectile function after radical prostatectomy (with preservation of at least 1 neurovascular bundle), a recovery time of 6 to 18 months is not uncommon. As this is also the usual time required for regeneration of spinal nerves, we believe that regeneration of cavernous nerves, partially damaged inadvertently, may be responsible. In a rat model, we examined the long-term effect of unilateral and bilateral cavernous nerve transection on the nonadrenergic/noncholinergic (NANC) nervous system and erectile function. In 31 rats, nitric oxide synthase (NOS), the enzyme that catalyzes nitric oxide production, was identified in penile nerve fibers from a mid-shaft segment with nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining and antibody to neuronal NOS. Animals were divided into three groups: 5 rats underwent pelvic exploration without transection of cavernous nerves (sham group); 13 rats underwent unilateral neurotomy of a 5-mm. segment of the cavernous nerve; and 13 rats underwent bilateral neurotomy. After bilateral ablation, the NOS-positive nerve fibers were significantly decreased at 3 weeks and remained so at 6 months; no erectile response could be elicited by pelvic nerve stimulation. After unilateral ablation, the NOS-positive nerve fibers were similarly decreased on the side of the neurotomy at 3 weeks, but by 6 months the number had increased significantly and approximated the level on the contralateral side. Furthermore, electrostimulation of the intact side induced a greater intracavernous pressure response at 6 months than at 3 weeks (N.B. the rat has an incomplete septum). Fibers positive for NOS were also identified in the dorsal nerve. The staining pattern diminished as rapidly and significantly on the side of neurotomy as in tissue from the corpus cavernosum. However, regeneration was not seen. To our knowledge, this is the first demonstration of regeneration of NOS-containing nerves after cavernous nerve neurotomy. Our findings support the reports by others that unilateral nerve-sparing is sufficient to preserve erectile function.

Amino Acid Oxidoreductases↗
PubMed1995

The effect of intracavernous injection of potassium channel openers in monkeys and dogs.

Cavernous smooth muscle relaxation is effected through a complex biochemical pathway; therefore, a defect in any step of this pathway may result in erectile dysfunction. Administration of pharmacologic agents which cause relaxation of the cavernous smooth muscle through a different mechanism may serve as an effective therapeutic alternative for impotent patients. To test this hypothesis two potassium channel openers, pinacidil and cromakalim, were used to initiate and maintain cavernous smooth muscle relaxation. The drugs were given as intracavernous injections in two animal models. In 10 dogs pinacidil and cromakalim produced full erection. With pinacidil (10(-2) M), the mean intracavernous pressure increased from a baseline pressure of 32.6 +/- 3.43 cm H2O to a peak intracavernous pressure of 131.8 +/- 12.01 cm H2O, and remained elevated for a period of 17.8 +/- 9.4 min. With cromakalim (10(-2) M) intracavernous pressure rose from a baseline pressure of 32 +/- 2.55 cm H2O to a peak intracavernous pressure of 140 +/- 3.39 cm H2O, for a period of 19.4 +/- 0.89 min. Additionally, in 5 primates injected with cromakalim (10(-2) M) intracavernous pressure rose from 24 +/- 3.81 to 131.2 +/- 7.56 cm H2O, for 27.0 +/- 4.79 min. It is concluded that both pinacidil and cromakalim can initiate and maintain erection in dogs and that cromakalim produces a similar erectile response in monkeys. Further study of the local and systemic effects of chronic injection is needed to determine whether this class of pharmacologic agents can provide therapy for impotent patients.

Animals↗
PubMed1994

The distribution of elastic fibrous elements within the human penis.

OBJECTIVE: To determine the distribution of elastic fibres in the tunica albuginea and the erectile tissue of the penis. MATERIALS AND METHODS: Samples of tunica albuginea or penile erectile tissue were taken from seven cadavers and five patients undergoing surgery. Light and electron microscopy were performed. RESULTS: There were two anatomical regions in which elastic fibres were seen rarely: the proximal crus and the distal tunica. In the rest of the corpora cavernosa where the tunica was more compliant, the elastic fibres were in relative abundance. In the corpus spongiosum, abundant irregularly oriented elastic fibres were present; the densest elastic network was found in the glans penis and was composed of coarse elastic fibres. A perisinusoidal fibroelastic shell was seen in the glans, which was probably an extension of Buck's fascia. The elastic components within the sinusoids (cavernosal, spongiosal, and glanular) were similar but finer than the elastic lamellae in the penile arterial wall. CONCLUSION: The elastic fibres were unevenly distributed, often forming an irregular network on which the collagen component rested. Elastic fibres were more abundant in the corpus spongiosum, around the blood vessels and surrounding the sinusoid of the corpus cavernosum.

Collagen↗
PubMed1993

Nitric oxide synthase: a new diagnostic tool for neurogenic impotence.

Cavernosal biopsy specimens obtained from men undergoing penile surgery permitted determination of the diagnostic value of nitric oxide synthase in neurogenic impotence. In biopsy specimens obtained from 25 men, the presence of nitric oxide synthase (NOS), as shown by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase staining, was determined in nerve fibers, smooth muscle, and sinusoidal endothelium. Positive staining for NOS correlated significantly (p < or = 0.001) with a clinical history of cavernous nerve integrity. In comparison, staining with protein gene product (PGP 9.5), an excellent general nerve stain, lacked any degree of specificity as an indicator of nerve status. NADPH diaphorase may provide important insight into the cavernous nerve integrity of the patient. This report is the first to describe histologic features of human cavernosal tissue biopsies that will allow the direct diagnosis of neurogenic impotence owing to cavernous nerve damage.

Amino Acid Oxidoreductases↗
PubMed1993

Can a venous patch graft be a substitute for the tunica albuginea of the penis?

We describe our experience with plaque excision and placement of a venous patch graft. Sprague Dawley rats (n = 20) underwent excision of a wedge of tunica albuginea with the defect covered by a segment of detubularized femoral vein, endothelial side towards the cavernous tissue. Erectile function, as determined by the rise in intracavernous pressure with cavernous nerve stimulation (mean 54.0 +/- 4.2 cm. H2O), was equal to that in a group of 10 intact age-matched controls (mean 46.9 +/- 3.37 cm. H2O). Penile cross-sections stained with Hart's elastic fiber stain or Trichrome stain revealed only minimal fibrosis in the region of the patch. In 3 dogs, a wedge of tunica was removed, and the defect was covered with a segment of detubularized deep dorsal vein. When sacrificed at 3 months, all animals had retained their erectile function with histologic evidence of minimal fibrosis. On the basis of histologic and functional data, the venous patch appears to be a reasonable alternative substance to those in common use.

Animals↗
PubMed1992

Interstitial cystitis: increased sympathetic innervation and related neuropeptide synthesis.

To investigate the possibility of a neural deterioration of the bladder wall in interstitial cystitis, bladder tissue from 10 patients with interstitial cystitis was compared with that from 10 control subjects by means of immunohistochemistry. An enhanced innervation of the bladder in the submucosa and detrusor muscle was found to represent an increase of sympathetic but not cholinergic neurons. In interstitial cystitis the number of neurons positive for vasoactive intestinal polypeptide and neuropeptide Y was higher and carried a larger number of axonal varicosities, whereas the number of neurons positive for substance P and calcitonin-gene-related peptide was not significantly different in both groups. We conclude that interstitial cystitis is associated with increased sympathetic outflow into the bladder and altered metabolism of vasoactive intestinal polypeptide and neuropeptide Y. Since similar changes have been observed in other inflammatory diseases of a presumably autoimmune nature, such as rheumatoid arthritis, Crohn's disease and colitis ulcerosa, the pathophysiology of interstitial cystitis may share common pathways with the latter. Experience in these diseases may facilitate a better understanding of the pathophysiology of interstitial cystitis and suggest new therapeutic concepts.

Adrenergic Fibers↗
PubMed1991

Loss of penile erectile response to intracavernous injection of acetylcholine in castrated dog.

Castrated dogs showed a slightly weak erectile response to cavernous nerve stimulation compared with normal dogs. Intracavernous injection of acetylcholine induced a dose-dependent increase of intracavernous pressure in normal dogs, however, there was almost no penile response in castrated dogs. Histological study showed a significant higher ratio of collagen tissue/smooth muscle in the corpus cavernosum of castrated dogs, but no difference in acetylcholine-esterase staining and the number of endothelial cells lining the sinusoidal spaces between castrated and normal dogs. These results indicate that the corpus cavernosum of castrated dogs nearly lost responsiveness to acetylcholine probably due to a high ratio of collagen/smooth muscle fibers and that there are different mechanisms for erectile response to nerve stimulation and intracavernous injection of acetylcholine.

Acetylcholine↗
PubMed1990

Down's syndrome: different distribution of congenital heart diseases between the sexes.

We have investigated the reasons why female patients with Down's syndrome prevail in our out-patient clinic for Paediatric Cardiology compared to the higher incidence of Down's syndrome among live born male children. We reviewed 277 cases of Down's syndrome, 119 males (42.96%) and 158 females (57.04%) from 1970 to 1987. A final diagnosis of the type of the congenital heart disease was accomplished among 210 cases, 85 males (40.47%) and 125 females (59.38%). This different distribution between the sexes was significant (P less than 0.01) when compared to that of the general population with congenital heart disease (4150 patients, 2108 males and 2042 females). The dominant lesion was atrioventricular septal defect, (130 cases; 46 males [54.11%] and 84 females [67.20%]). We found an identical incidence of this lesion among patients without Down's syndrome. In the studied population, we did not find any of the congenital heart diseases usually prevalent in males, such as aortic coarctation or stenosis and complete transposition. The molecular determinants of Down's syndrome seem to influence the preponderance of atrioventricular septal defect in females, increasing its incidence, while seeming to act in a negative way concerning congenital heart diseases usually showing male prevalence.

Down Syndrome↗