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Biomedical subjects

F Giuliano

Publications and source records attributed to F Giuliano.

At least 91 records · Page 5Linked to original sources

Neural control of penile erection in the rat.

The role of autonomic and somatic neural pathways involved in the control of penile erectile tissue was investigated in an in vivo rat model. Intracavernous pressure (ICP) changes were recorded during single or combined electrical stimulation of peripheral nerves in anesthetized rats. Stimulation of the pelvic and cavernous nerves elicited similar ICP increases. Ganglionic blockade abolished the response to pelvic nerve stimulation. Stimulation of the hypogastric nerve, the sensory or motor branches of the pudendal nerve, or the paravertebral sympathetic chain at L4-L5 by themselves did not produce any change in ICP. Stimulation of some of these nerves caused changes in ICP when combined with cavernous nerve stimulation. Stimulation of the paravertebral sympathetic chain reduced the ICP increases elicited by cavernous nerve stimulation. A decrease in ICP in response to cavernous nerve stimulation was also elicited by stimulation of the peripheral cut end of the sensory branch of the pudendal nerve or in paralyzed rats, the motor branch of the pudendal nerve. After sectioning the two branches of the pudendal nerve, stimulation of the sympathetic chain still reduced the ICP increase in response to cavernous nerve stimulation. Stimulation of the motor branch of the pudendal nerve during erection elicited by cavernous nerve stimulation was responsible for an additional ICP increase, which reached suprasystolic values. The present study confirms a proerectile role for parasympathetic pathways. Sympathetic fibers conveyed in both branches of the pudendal nerve exert an antierectile role in the rat. We identified an antierectile sympathetic outflow, originating in the caudal sympathetic chain, the anatomical arrangement of which remains unknown. In this model, penile erection appeared to be dependent on the recruitment of sacral parasympathetic outflow. Additional recruitment of efferent somatic fibers present in the motor branch of the pudendal nerve could participate in more rigid erection. This study provides new information about the organization of the pathways through which the rat penis is innervated, and would be of interest to investigators in the field of male sexual function.

Anesthesia↗

Intracavernous pressure changes during reflexive penile erections in the rat.

Reflexogenic penile erections have been previously described in the rat. However, exact involvement of the corpus cavernosum in reflex responses is indefinite. We report changes in intracavernous pressure (ICP) recorded in 10 awake rats by means of a telemetric device. The ICP changes and penile reflex responses (lengthening of the penile body, glans erection, cup, and flip) were recorded during ex copula tests. Each type of penile response was characterized by a specific ICP variation. Mean maximal ICP increase during lengthening of the penile body was 58.6 mmHg, during glans erection 67.3 mmHg, during cups 99.1 mmHg, and 215.2 mmHg during flips. ICP increases to 35.1 mmHg immediately preceding each cluster of penile responses. This study provides quantitative data on the involvement of the corpus cavernosum during reflexive erections. Tumescence of the corpus cavernosum was present during glans erection and suprasystolic ICP peaks occurred during flips. ICP measurements during reflexive erections should bring new insights into the analysis of their physiological mediation.

Animals↗

[Erection disorders: efficacy and tolerability after 6 months of intracavernous self-injections of alprostadil. Groupe Français d'Etude de l'Alprostadil].

OBJECTIVES: Self-administered intracavernous injections, notably with alprostadil are currently the most widely used non-psychotherapeutical treatment of erectile dysfunction. We assessed the effectiveness of this treatment after 6 months of self-injections. METHODS: Efficacy, acceptability and tolerance to alprostadil self-administered via intracavernous injections for 6 months was evaluated in 144 men, age 24 to 72 years, and followed monthly after an initial training period and search for the optimal dose. RESULTS: The mean number of self-injections was 5.5 at a mean dose of 18.6 micrograms per injection. From the first to sixth month, the frequency of complete erections after self-injection rose from 62% to 77% and failures declined from 8% to 3%. After six months, 40% of the patients had abandoned the treatment including 9% who abandoned during the first month, usually due to poor acceptance and because of cure in two patients (4.5%). Patients reported sexual intercourse after self-injections as satisfactory in 81% of the cases; 66% of their partners reported satisfactory intercourse. Tolerance assessment revealed pain in 14% of the patients and decreasing effect with time in two patients who discontinued self-injections for this reason. Other undesirable side effects were infrequent, usually related to technical injection errors and decreasing effect with time. One case of priapism and two indurations of the cavernous bodies were also observed. CONCLUSION: Self-administration of intracavernous alprostadil can lead to rigid erection in patients with erectile dysfunction. Patients are generally well satisfied and tolerance is good.

Adult↗

Physiological evidence of neural pathways involved in reflexogenic penile erection in the rat.

To elucidate neural pathways responsible for the occurrence of reflexogenic erections, the response of the corpus cavernosum to electrical stimulation of the dorsal nerve of the penis (DNP) was measured in anesthetized, acutely spinalized rats. Stimulation elicited a dramatic increase in intracavernous pressure (ICP). ICP response was decreased by 70% after sectioning the pelvic nerve homolaterally to the stimulated DNP and abolished after bilateral section. ICP response was not impaired by curarization, but its latency was lengthened. Thus we physiologically evidenced a reflex loop independent from supraspinal centers between DNP and the pelvic nerve supporting penile reflexogenic erection.

Animals↗

[Diagnosis and treatment of impotence. Indications of intracavernous injections].

Based on progress in our understanding of the physiology of erection, intracavernous injections of vasoactive substances have completely changed the treatment of impotence. Essentially, erection results from the effect of smooth muscle relaxation in the vascular walls leading to local fall in vascular resistance and increased arterial flow combined with smooth muscle relaxation within the sinusoid spaces of the cavernous bodies. Smooth muscle cell tone is regulated not only by the classical norepinephrine and acetylcholine neurotransmitters, but also by other non-adrenergic and non-cholinergic neurotransmitters released locally. Although the "erectile neurotransmitter" has not been identified parasympathetic nerve terminaisons release nitric oxide (NO) a powerful myorelaxant agent. NO is also synthetized by the endothelial cells on the internal surface of the sinusoidal spaces. These recent findings have led to the use of papaverin to reduce the level of intracellular calcium, alpha-blockers to antagonize alpha-receptor and prostaglandin to inhibit norepinephrine release. Vasoactive intestinal polypeptide, a myorelaxing agent, and linsidomine which favours NO release have also been used. Diagnostic tests by intracavernous injections are indicated as part of the complete work-up in patients consulting for impotence. Therapeutic indications for auto-injections require careful choice of the agent and the dosage to inject depending on the cause of the impotence and the patient's demands and capacity to learn the technique. Papaverin or prostaglandin E1 alone or in combination with phentolamine give good results. Rigid erections can be obtained in over 60% of the patients. Alpha-blockers appear to be the least active in terms of rigidity. Mid-term results of intracavernous fibroses have been reported after papaverine injections. Priapism is the main secondary effect of intracavernous injections.

Humans↗

A large proportion of pelvic neurons innervating the corpora cavernosa of the rat penis exhibit NADPH-diaphorase activity.

Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, which indicates the presence of neural nitric oxide synthase, the enzyme responsible for the generation of nitric oxide, was used in combination with retrograde labelling methods to determine, in whole-mounts and sections of rat major pelvic ganglia, whether neurons destined for the penile corpora cavernosa were able to produce nitric oxide. In whole-mount preparations of pelvic ganglia, among the 607 +/- 106 retrogradely labelled neurons innervating the penile corpora cavernosa, 84 +/- 7% were NADPH-diaphorase-positive, 30 +/- 7% of which were intensely histochemically stained. In serial sections of pelvic ganglia, out of a mean count of 451 retrogradely labelled neurons, 65% stained positively for NADPH-diaphorase. An average of 1879 +/- 363 NADPH-diaphorase positive cell bodies was counted in the pelvic ganglion. In the major pelvic ganglion, neurons both fluorescent for Fluorogold or Fast Blue and intensely stained for NADPH-diaphorase were consistently observed in the dorso-caudal part of the ganglia in the area close to the exit of the cavernous nerve and within this nerve. This co-existence was much less constant in other parts of the ganglion. In the rat penis, many NADPH-diaphorase-positive fibres and varicose terminals were observed surrounding the penile arteries and running within the wall of the cavernous spaces. This distribution of NADPH-diaphorase-positive nerve cells and terminals is consistent with the idea that the relaxation of the smooth muscles of the corpora cavernosa and the dilation of the penile arterial bed mediated by postganglionic parasympathetic neurons is attributable to the release of nitric oxide and that nitric oxide plays a crucial role in penile erection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Anatomy of the prostatic nerves.

The entire prostate of a 10 year old boy was cut with a microtome in to 4300 serial slices. The nerves were stained using a monoclonal antibody called anti PS 100. All information was recorded using a computer reconstruction programme. The prostatic nerve supply is very abundant. The nerve fibers of the cranial prostate (central zone) follow a pathway parallel to the anterior surface of the seminal vesicles going towards the caudal prostate. The periurethral zone is widely innervated by nerves arising from the periphery. The caudal prostate also contains many nerve fibers of variable size. We identified many nerve fibers along the anterior surface of the seminal vesicles and surrounding the lateral aspect of the prostatic capsule. They penetrate the capsule and the whole circumference of the caudal prostate. The prostatic capsule is covered by numerous nerve fibers and ganglia, which form a true periprostatic nerve network. The urethra is supplied by numerous thick fibers of more than 30 microns in diameter.

Child↗

Telemetric monitoring of intracavernous pressure in freely moving rats during copulation.

Changes in intracavernous pressure (ICP) were recorded in freely moving rats by means of a catheter implanted in the corpus cavernosum and connected to a pressure transducer located subcutaneously. Intracavernous pressure changes and copulatory events (mounts, intromissions and ejaculations) were recorded during several overnight testing sessions with 12 rats in the presence of receptive females. Video recordings of sexual behavior in the implanted and nonimplanted rats revealed that the ICP device did not impair copulatory behavior. Comparison between copulatory behavior and ICP changes revealed that ICP profiles could identify the number of intromissions and ejaculations as well as the timing of these events. The results showed that during mounts, intromissions and ejaculations, ICP increases were 36.9 mm. Hg, 62 mm. Hg and 106.3 mm. Hg in 4 rats. The increases in ICP during mounts and intromissions appeared higher in sexually experienced as compared with sexually naive rats. These results demonstrate the reliability of the telemetric measurement of ICP in freely moving rats under natural physiological conditions. The model provides quantitative data for research on the neurophysiology of penile erection and evaluation of oral treatments for impotence.

Animals↗

Antierectile role of the sympathetic nervous system in rats.

The effects of the pharmacological changes of sympathetic innervation were studied in a rat model of electrically induced erection. Stimulation of the cavernous nerve elicited an erectile response measured by intracavernous pressure and separated into latency phase, tumescence (corresponding to corpora cavernosa filling), full erection (ICPE: intravenous pressure during full erection) and detumescence (corpora cavernosa emptying). A close dependence of the corpora cavernosa filling rate, ICPE and corpora cavernosa emptying rate on arterial blood pressure was demonstrated. Ganglionic blockade by mecamylamine decreased ICPE. Chemical sympathectomy by 6-hydroxydopamine improved the entire erectile response. Phentolamine (alpha-adrenoreceptor blocking agent) and propranolol (beta-adrenoreceptor blocking agent) increased the latency phase. Phentolamine increased the corpora cavernosa filling rate and the ICPE, while propranolol decreased them. These results demonstrate that a sympathetic inhibition decreases the erectile response to stimulation and that this inhibition is due not only to norepinephrine, but possibly to a nonadrenergic noncholinergic transmitter, colocalized with norepinephrine.

Animals↗

Electrophysiological study of relations between the dorsal nerve of the penis and the lumbar sympathetic chain in the rat.

Afferent sensory inputs from the penis are carried by the dorsal nerve of the penis (DNP) to the spinal cord. Sympathetic outflow involved in the control of the urogenital tract is partly conveyed by the lumbosacral sympathetic chain. Our aim was to search for a sympathetic component in the DNP and relations between DNP afferents and sympathetic fibers conveyed by the distal sympathetic chain in anesthetized adult male rats. Stimulation of the lumbar sympathetic chain at the L4-L5 level (LSC4-5) elicited an evoked discharge on the DNP. This discharge was abolished by cutting the sympathetic chain distal to the stimulation site. Ganglionic blockade with hexamethonium and various neural sections revealed the presence of sympathetic postganglionic fibers in the DNP, originating in the sympathetic chain. Stimulation of the DNP evoked a reflex discharge in the LSC. This reflex was spinally mediated since it was abolished by acute spinal cord transection at the L5 level. Acute spinalization at the T8 level significantly reduced the latency of the evoked response. We hypothesize that both spinal and supraspinal control exist over relations of the DNP afferents with sympathetic outflow to the pelvis. Increase in sympathetic tone elicited by activation of penile sensory fibers could play a role in regulation of sexual function.

Afferent Pathways↗

Potentially functional regions of nucleic acids recognized by a Kohonen's self-organizing map.

Computer recognition of short functional sites on DNA, such as promoter regions or intron-exon boundaries, has recently attracted much interest. In this paper we have focused our attention on the automatic recognition of relevant features of human nucleic acid sequences by means of an unsupervised artificial neural network model. Sixty messenger RNA and 31 genomic DNA sequences were analysed. The results showed that in mRNA, the minimal similarity 60 base pattern was guanine- and cytosine-rich and located in most sequences in a range of 250 bases from either the middle point of the signal peptide coding region or from the start of the coding region. On DNA sequences a region defined by a cluster of minimal similarity patterns was present in many of the analysed genes. This zone may be related to alternative splicing and DNA methylation.

Algorithms↗

Autonomic control of penile erection: modulation by testosterone in the rat.

The role of testosterone on peripheral autonomic control of penile erection was studied in rats. Erectile response to cavernous nerve stimulation was measured by intracavernous pressure associated with arterial blood pressure monitoring in anesthetized adult males. Comparison was performed between control (Co), castrated (Ox) and castrated, testosterone-replaced (OxT) rats. Ox rats exhibited smaller erectile responses. Testosterone replacement restored these responses in OxT rats. To identify the peripheral target of testosterone, postganglionic neurons of the major pelvic ganglion, innervating the corpora cavernosa through the cavernous nerves, were separated from the spinal cord by preganglionic axotomy of the pelvic nerves in three other groups of rats (PNx). Erectile response was unchanged in PNx rats, decreased in OxPNx more than in Ox rats, and restored by testosterone replacement (OxPNxT rats). We ruled out the participation of a somatic component in the erectile response in this model as there was no difference between curarized and Co rats. We infer that testosterone enhances the erectile response of cavernous nerve stimulation, acting peripherally to the spinal cord. Arguments are provided that the sites of action for testosterone or its metabolites are situated on neurons rather than on penile erectile tissue. Proerectile postganglionic parasympathetic neurons seem to be the exact target for gonadal steroids.

Animals↗

Identification of a new motif on nucleic acid sequence data using Kohonen's self-organizing map.

Here we present a performance test of a Kohonen features map applied to the fast extraction of uncommon sequences from the coding region of the human insulin receptor gene. We used a network with 30 neurons and with a variable input window. The program was aimed at detecting unique or uncommon DNA regions present in crude sequence data and was able to automatically detect the signal peptide coding regions of a set of human insulin receptor gene data. The testing of this program with HSIRPR cDNA release (EMBL data bank) indicated the presence of unique features in the signal peptide coding region. On the basis of our results this program can automatically detect 'singularity' from crude sequencing data and it does not require knowledge of the features to be found.

Algorithms↗

[Histologic identification of the afferent fibers of the pelvic plexus].

The inferior hypogastric (pelvic) plexus conveys two types of fibres: sympathetic fibres originating in the thoracolumbar sympathetic chain and parasympathetic fibers originating in the sacral anterior rami. By using a histofluorescent stain (glyoxalic acid) and a histochemical stain (thiocholine) in 17 fresh cadavres, we have demonstrated that the sympathetic fibres arise from sacral sympathetic ganglia. These fibres participate in the constitution of the pelvic splanchnic nerves. In this study, we confirm that the inferior roots of the pelvic plexus are not only parasympathetic, but also sympathetic.

Adrenergic Fibers↗

[Acute effects of transdermal administration of nitroglycerin on effort tolerance and myocardial perfusion, evaluated by Tl-201 scintigraphy, in patients with stable effort angina].

The aim of this study was to evaluate the effects of the transdermal application of nitroglycerin (NGT) on exercise tolerated and regional myocardial perfusion, as evaluated by 201 thallium stress scintigraphy, in patients with stable effort angina. We studied 20 patients, 15 men and 5 women, aged between 43 and 68 years, with average age of 55 +/- 8 years, suffering from effort angina, whose angina threshold was stable in 3 stress testing performed in the week before the study started. The patients, after a pharmacological washout of 1 week, underwent 2 exercise testing 20 hours after the application of a patch containing placebo or 10 mg NGT, with an interval of 7 days. 60-90 s before stress testing was interrupted, 2 mCi of thallium 201 were injected in an antecubital vein of the arm. The scintigraphic images were obtained soon in the 0, 45 and 90 degree views and after 4 hours reperfusion. Under placebo patch all patients interrupted ergometer test for angina, while under the patch containing active NGT angina was present in 11/20 patients and 9 patients stopped the test because of muscular exhaustion. NGT induced an increase of the ergometer test duration (+26%); this difference was statistically significant. The ST segment downsloping decreased significantly both at maximal common work and at exercise peak after NGT application in comparison with placebo. The perfusional defects observed on the scintigraphic images obtained soon after the exercise (and reversible after 4 hours of reperfusion) on placebo patch, diminished significantly after NGT and the captation index lung/heart decreased also significantly (from 49 to 41%), showing so an improvement of cardiac performance. In conclusion the transdermal application of NGT, in patients with effort angina, demonstrated to have antianginal and antiischemic effect, reducing the number of patients interrupting the stress testing for angina, increasing the exercise tolerated and diminishing the ST segment downsloping, objective demonstration of myocardial ischemia. This antianginal and antiischemic effect might follow to the reduction of the preload induced by nitrates, in part also the reduction of the afterload, factors determining a decrease of the wall tension and so of MVO2, but also to a redistribution of the subendocardial flow as demonstrated by 201-Tl scintigraphic images. These effects induce also a global improvement of the left ventricular function as demonstrated by the reduction of the lung/heart index of thallium captation.

Administration, Cutaneous↗

[Anuria associated with an aorto-iliac aneurysm. Apropos of a case].

The authors report a case of a perianeurysmal retroperitoneal fibrosis (RPF) with oligoanuric renal failure. A complete assessment was performed with computed tomography. Bilateral ureteral catheterization restored normal renal function and allowed surgical treatment to be performed including an aorto-iliac replacement and a bilateral ureterolysis with intra-peritoneal diversion of the ureter. A review of the literature revealed 15 similar cases. Pathophysiology and treatment of the retroperitoneal peri-aneurysmal fibrosis are discussed.

Aneurysm↗

Asymptomatic episodes of ischaemia and their relation to heart rate changes in patients with chronic ischaemic heart disease.

The aim of our study was to evaluate the prevalence of asymptomatic episodes of ischaemia and their relation to heart rate in patients with effort angina pectoris undergoing continuous electrocardiographic monitoring for 24 h. We studied 91 patients with typical history of effort angina and positive stress testing (angina and rectilinear or downsloping ST segment depression more than 1 mm). During electrocardiographic monitoring 81 patients showed symptomatic or asymptomatic ischaemic episodes with ST segment depression, four patients a T wave inversion, while six patients did not show ischaemic episodes. The total number of ischaemic episodes registered was 284, of which 106 (37.32%) were symptomatic with significant heart rate increase, 130 (45.78%) asymptomatic with heart rate increase and 48 (16.9%) asymptomatic without heart rate changes. Twelve patients (13.18%) showed only symptomatic episodes of ischaemia with increase of heart rate, 26 patients (28.57%) symptomatic and asymptomatic episodes with heart rate enhancement, 12 patients (13.18%) only asymptomatic episodes with heart rate increase, eight patients (8.79%) symptomatic episodes of ischaemia with heart rate increase and asymptomatic ones with and without heart rate changes, and finally 23 patients (25.57%) showed symptomatic episodes with heart rate increase and asymptomatic ones without heart rate changes. In total, 31 (34.06%) of these patients showed during continuous electrocardiographic monitoring asymptomatic episodes of ischaemia without heart rate changes. These findings suggest a possible intervention of coronary tone modifications in determining asymptomatic ischaemic episodes without heart rate change in patients with effort angina.

Adult↗