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Biomedical subjects

L Nunes

Publications and source records attributed to L Nunes.

15 recordsLinked to original sources
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↗
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↗
PubMed1989

Androgen sensitivity of rat prostate carcinoma studied by 31P NMR spectroscopy, 1H MR imaging, and 23Na MR imaging.

31P NMR spectroscopy, 1H magnetic resonance (MR) imaging, and 23Na MR imaging were used to study the biochemical difference between nine hormone-sensitive and six hormone-resistant rat prostate cancers and to follow bioenergetic and morphologic changes subsequent to androgen deprivation in the hormone-sensitive model. Neither 1H nor 23Na MR image characteristics were useful in distinguishing androgen-sensitive from androgen-resistant prostate cancer nor in identifying androgen deprivation. 31P NMR spectroscopy did detect bioenergetic differences between the hormone-sensitive and hormone-resistant tumors. Baseline spectra showed a significantly higher PCr/ATP ratio (mean 0.86 +/- 0.09 SEM) for hormone-sensitive tumors than for hormone-resistant tumors (mean 0.26 +/- 0.07 SEM). By 3 days after androgen deprivation (orchiectomy (castration], PCr/ATP ratios had decreased noticeably; by 1 week, the decrease was statistically significant and remained so for the rest of the study (3 weeks). It appears that 31P NMR spectroscopy is useful in detecting androgen sensitivity of prostatic carcinoma.

Androgens↗
PubMed1989

Semen manipulation: improved sperm recovery and function with a two-layer Percoll gradient.

The authors compared a simple, two-layer Percoll density gradient technique with the swim-up technique for semen preparation in 128 men. In samples from normospermic (n = 55), oligospermic (n = 26), and asthenospermic (n = 29) men, the Percoll technique significantly improved yield, percent motility, and absolute number of motile sperm recovered, but in samples from oligoasthenospermic men (n = 18), only percent motility was improved. The Percoll density gradient also selected sperm with markedly improved function as assessed by both the sperm penetration assay and the fertility index. In 37 samples negative on the sperm penetration assay when processed with the swim-up technique, 19 (51%) became positive when processed with the Percoll technique. The Percoll density gradient is an improved method for semen manipulation as it allows greater recovery of sperm with higher motility and improved sperm function.

Adult↗
PubMed1989

Acetylcholine as a possible neurotransmitter in penile erection.

We investigated the erectile response to intracavernous injection of increasing doses of acetylcholine (0.5 to 500 micrograms.) in 10 monkeys. To differentiate between nicotinic (ganglionic) and muscarinic (parasympathetic postganglionic) effects, acetylcholine was likewise administered after 1.6 mg. trimethaphan camsylate and 0.1 mg. atropine, alone or sequentially. Erections were induced by cavernous nerve stimulation before and after atropine. Acetylcholine induced a dose-dependent, triphasic erectile response: a first tumescence phase followed by contraction and a subsequent second phase of tumescence. Atropine reduced but did not abolish the erectile response to acetylcholine: attainment of maximal intracavernous pressure after neurostimulation was both delayed and reduced (mean 25 cm. H2O). Only after combined nicotinic and muscarinic blockade was the erectile response to acetylcholine completely abolished. Histologic staining for acetylcholinesterase in five additional monkeys that had not received acetylcholine showed dense staining within the cavernous erectile tissue and around the cavernous arteries. Our data suggest that acetylcholine is a possible neurotransmitter for penile erection in monkeys.

Acetylcholine↗