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Biomedical subjects

F Giuliano

Publications and source records attributed to F Giuliano.

At least 73 records · Page 4Linked to original sources

Electrical activity from rat corpora is affected by pharmacological but not mechanical intracorporal manipulation.

Smooth muscle electromyographic (EMG) recording from the corpora cavernosa is a potentially useful clinical tool for the diagnosis of impotence. Controversy still exists regarding the nature of this signal, which could be resolved using animal models. The signal recorded from denuded rat corporal surface was Fourier transformed, and power at 0.01-1 Hz was calculated. Measurements were taken in the flaccid state and during erection induced by intracorporal injection of smooth muscle relaxants [the phosphodiesterase inhibitors papaverin and isobutylmethylxanthine (IBMX)]. Recorded activity decreased significantly during the pharmacologically evoked erection: the mean square root power of 250.7+/-137.1 microV decreased to 49.8+/-14.1 microV (P<0.0001) after papaverin, and IBMX caused it to decrease from 222.8+/-132.0 microV to 58.1+/-40.8 microV (P<0.0001) (mean +/- SD). Intracorporal injection of adrenaline partially reversed the response, increasing activity to 135.3+/-72.3 microV (P=0.01) and 137.5+/-122.6 microV (P=0.015), respectively, in parallel with detumescence. In order to rule out a mechanical artefactual explanation for these results, recording was also performed before and during artificial erection induced by the intracorporal infusion of saline. This manipulation did not cause any change in corporal activity, despite corporal engorgement and increased pressure. In conclusion, the signal indeed reflects changes in the tone of corporal smooth muscle, and therefore should be regarded as a genuine EMG recording.

1-Methyl-3-isobutylxanthine↗

Oxytocinergic and serotonergic innervation of identified lumbosacral nuclei controlling penile erection in the male rat.

Penile erection is due to activation of proerectile neurons located in the sacral parasympathetic nucleus of the L6-S1 spinal cord in the rat. Contraction of the ischiocavernosus and bulbospongiosus striated muscles, controlled by motoneurons located in the ventral horn of the L5-L6 spinal cord, reinforces penile erection. Physiological and pharmacological arguments have been provided for a role of oxytocin and serotonin in the spinal regulation of penile erection. Immunohistochemistry of oxytocinergic and serotonergic fibres was performed at the lumbosacral level of the male rat spinal cord, and combined with retrograde tracing from the pelvic nerve or from the ischiocavernosus and bulbospongiosus muscles using wheat germ agglutinin-horseradish peroxidase. Sacral preganglionic neurons retrogradely labelled from the pelvic nerve formed a homogeneous population, predominant at the L6 level. Motoneurons retrogradely labelled from the ischiocavernosus and bulbospongiosus muscles were observed in the medial part of the dorsolateral and in the dorsomedial nuclei. Fibres immunoreactive for oxytocin were mainly distributed in the superficial layers of the dorsal horn, the dorsal gray commissure and the sacral parasympathetic nucleus. Some of these fibres were apposed to retrogradely-labelled sacral preganglionic neurons and at the ultrastructural level, some synapses were evidenced. Fibres immunoreactive for serotonin were largely and densely distributed in the dorsal horn, the dorsal gray commissure, the sacral parasympathetic nucleus and the ventral horn. Some serotonergic fibres occurred in close apposition with retrogradely-labelled sacral preganglionic neurons and motoneurons, and synapses were demonstrated at the ultrastructural level. This study provides morphological support for a role of oxytocin and serotonin on sacral preganglionic neurons innervating pelvic organs and motoneurons innervating the ischiocavernosus and bulbospongiosus muscles.

Animals↗

Expression of alpha 1 adrenoceptor subtypes in rat corpus cavernosum.

Norepinephrine mediates the antierectile role of the sympathetic nervous system. It binds to postsynaptic alpha 1 adrenoceptors present on smooth muscle fibers of the corpus cavernosum. Receptor cloning studies have evidenced three alpha 1 adrenoceptor subtypes: alpha 1A, alpha 1B and alpha 1D. We searched for the presence of these three alpha 1 adrenoceptor subtypes in the rat corpus cavernosum using in situ hybridization with specific oligonucleotide probes. Brain tissue was used as the reference of probes specificity. Autoradiographic films were studied with light illumination and computer-assisted densitometry using an image analyser. We provide evidence that the three alpha 1 adrenoceptor subtypes are expressed in the rat corpus cavernosum. These three subtypes appear to be more expressed in the trabecular smooth muscle fibers than in vascular smooth muscle fibers. Further experiments are needed to determine whether the proportion of alpha 1 adrenoceptor subtypes changes according to the etiology of erectile dysfunction. This morphological approach provides a basis for future pharmacological research of specific alpha 1 adrenoceptor subtypes blocking agents designed to treat erectile dysfunction.

Animals↗

[Treatment for impotence].

For the treatment of erectile dysfunction, the authors recommend that prostheses be reserved for cases refractory to all other treatments. Local treatments by injection of erectogenic substances consist of paraverine and prostaglandin E1. A new oral treatment is also available, not with yohimbine or apomorphine, but with sildenafil (viagra).

3',5'-Cyclic-GMP Phosphodiesterases↗

Spinal control of penile erection.

Smooth muscle relaxation of penile arteries, the corpus cavernosum, and the corpus spongiosum, leading to penile erection, results from parasympathetic neural pathway activation and, likely, simultaneous inhibition of sympathetic outflow. Proerectile parasympathetic outflow is reflexively activated by sensory information of peripheral origin, conveyed by the dorsal penile nerve, and reflexive erections are supported by an intraspinal circuitry. Supraspinal influences modulate the reflex. Information integrated at or originating from supraspinal structures may also elicit penile erection. Several neurotransmitters are involved in either the modulation of the spinal reflex or the mediation of supraspinal influences. Spinal cord injury differently alters reflexive penile erection or erection from a central origin, depending on the neurologic level of injury.

Animals↗

Penile arteries in humans. Origin--distribution--variations.

The arterial supply to the penis remains unclear. The frequency of occurrence and functional significance of accessory pudendal arteries remains controversial and it has been suggested that the presence of variations is correlated with atheromatous disease involving internal pudendal arteries. We dissected pelvic and penile arteries in 20 adult fresh male cadavers. The results are expressed according to age and the presence of atherosclerosis. Three patterns of penile arterial supply can be described: type I arising exclusively from internal pudendal arteries (3/20), type II arising from both accessory and internal pudendal arteries (14/20) and type III arising exclusively from accessory pudendal arteries (3/20). This study emphasizes the findings previously reported by early anatomists. No correlation between the presence of accessory pudendal arteries and the extent of atheroclerosis was observed. Accordingly we postulate that these variations are usually congenital. Terminal branches of accessory pudendal arteries mainly supply the corpora cavernosa. As they are located very close to the prostate, the risk of injury is high during radical prostatectomy. The possibility of impotence from such injury after radical prostatectomy needs therefore to be reconsidered.

Aged↗

[Physiology of erection].

The peripheral pharmacology of local mechanisms of penile erection is known today thanks to recent advance in the study of the regulation of erectile tissue smooth muscle tone. Smooth muscle fibers present in the corpus cavernosum and arteries destined to the penis relax in response to the release of non adrenergic non cholinergic neuromediators synthetized by postganglionic parasympathetic nerve fibers present in the cavernous nerves. Nitric oxide is the main proerectile neuromediator. Noradrenaline, released by sympathetic fibers, contracts penile smooth muscle fibers and is antierectile. Recent progress in the peripheral pharmacology of penile erection allows new perspectives in the treatment of erectile dysfunction. The spinal cord represents a major site for the neural regulation of penile erection. The latter occurs in response to stimuli from peripheral or supraspinal origin. Different neural structures in the brainstem (nucleus paragigantocellularis), pons and hypothalamus (nucleus paraventricularis) send projections to the thoracolumbar sympathetic and lumbosacral parasympathetic nuclei at the origin of proerectile peripheral pathways. Serotonin and oxytocin are candidates as neuromediators involved in the supraspinal control of penile erection. Studying the central command of penile erection allows an approach to the pathophysiology of psychogenic erectile dysfunction.

Animals↗

Evidence of sympathetic fibers in the male rat pelvic nerve by gross anatomy, retrograde labeling and high resolution autoradiographic study.

Several arguments exist in various animal species and man for the presence of a sympathetic component in the pelvic nerve, classically regarded as parasympathetic. We tested this hypothesis in the male rat. Nerve bundles issued from the sacral region of the paravertebral sympathetic chain and reaching the S1 spinal nerve were identified. Neurons in the sacral parasympathetic nucleus of the L6-S1 spinal cord and in the L2-S1 paravertebral sympathetic chain were retrogradely labeled from the pelvic nerve. Radioautography evidenced labeling of unmyelinated fibers in the pelvic nerve following in vitro incubation with 3H-noradrenaline. A population of sympathetic fibers issued from the lumbosacral sympathetic chain exists in the pelvic nerve of the male rat. This qualitative study provides a morphological basis to uncover the role of the sympathetic outflow present in the pelvic nerve.

Animals↗

Spinal Fos labeling and penile erection elicited by stimulation of dorsal nerve of the rat penis.

Penile afferents present in the dorsal nerve of the penis (DNP) convey sensory information from the penis to the spinal cord and represent the afferent limb of reflexive erections. Immunocytochemical staining of Fos was used to identify spinal neurons that receive excitatory inputs from the DNP in anesthetized rats. Intracavernous pressure (ICP) was recorded as an index of erection. Dissection as well as stimulation of the DNP elicited a comparable increase in Fos staining. Labeling was present in the dorsal horn, the dorsal gray commissure, and the sacral parasympathetic nucleus, supporting the hypothesis of direct or indirect afferent projection from the penis and penile sheath in these areas. No change in ICP was observed in these rats. Stimulation of the DNP elicited both increased Fos labeling and ICP after spinalization, demonstrating the presence of a supraspinal inhibitory control exerted on the polysynaptic intraspinal circuitry responsible for reflexive penile erection.

Afferent Pathways↗

Erectile response to hypothalamic stimulation in rats: role of peripheral nerves.

The role of peripheral parasympathetic and sympathetic pathways was explored in erectile responses elicited by hypothalamic medial preoptic area (MPOA) stimulation in adult male anesthetized rats. Under control conditions, MPOA stimulation reliably elicited erectile responses evidenced by an increase of the intracavernous pressure-to-blood pressure ratio. The erectile response was abolished by 1) acute bilateral section of cavernous or pelvic nerves or cauda equina and 2) chronic lesions of pelvic nerves or cauda equina. Acute section of the hypogastric nerve did not significantly decrease the erectile response. The erectile response was significantly depressed after acute or chronic sections of the paravertebral sympathetic chain at the L4-L5 level or chemical sympathectomy with 6-hydroxydopamine. The decrease due to acute sympathetic chain lesion was reversed by bilateral ligation of the external iliac arteries. Accordingly MPOA stimulation elicits erectile responses via 1) activation of the parasympathetic outflow conveyed by the pelvic and cavernous nerves and 2) activation of neural fibers conveyed by the sympathetic pathways. We propose that sympathetic fibers running in the paravertebral sympathetic chain are responsible for vasoconstriction of nonpenile areas to divert blood to the penis, allowing the dramatic increase of penile arterial inflow required for erection.

Animals↗

[Central nervous system control of erection].

Relaxation of arterial and cavernous smooth muscle fibers, leading to the filling of the sinusoidal spaces with blood, are the local mechanisms of erection. Smooth muscle relaxation results from activation of parasympathetic neural pathway and probably simultaneous inhibition of the sympathetic outflow. Reflexive erection elicited by recruitment of penile afferents conveyed by the dorsal penile nerve involves both autonomic and somatic efferents. This reflex is mediated at the spinal cord level and modulated by supraspinal influences. Serotonergic pathways originating in the raphe nuclei mediate inhibitory control on reflexive erection. Several hypothalamic areas such as the medial preoptic area and the paraventricular nucleus are the source of descending pathways and/or represent important integrating centers. Dopamine acting at the medial preoptic area level may regulate penile erection. Neuroendocrine regulation may vary depending on the context in which erection occurs, for example, coitus, in response to extrinsic or psychogenic stimuli, and rapid eye movement sleep.

Afferent Pathways↗

Stimulation of the medial preoptic area of the hypothalamus in the rat elicits increases in intracavernous pressure.

Penile erection can be elicited by various stimuli integrated in the spinal cord and/or higher central nervous structures. The medial preoptic area (MPOA) of the hypothalamus is known to play a key role in the regulation of the male sexual behavior. In anesthetized male rats we performed MPOA stimulation via stereotaxically implanted electrodes or canulae delivering L-glutamate. An erectile response, assessed by an increase of intracavernous pressure (ICP), was recorded during electrical stimulation of the MPOA. Stimulating the posterior region of the MPOA elicited a greater erectile response than stimulation applied to the anterior region. Microinjections of L-glutamate also elicited an ICP increase. Stimulation of MPOA neurons therefore elicits activation of neural pathways controlling penile erection.

Analysis of Variance↗

[Experimental approach to reflex erection in rats: modeling and functional neuroanatomy of the involved nerve pathways].

The neurophysiology of erection remains poorly elucidated, particularly at the spinal cord level. We studied variation of intracavernous pressure (ICP) in rats. Tactile stimulation of the prepuce in conscious rats induces the appearance of sequences of reflex erectile responses affecting the corpora cavernosa and/or corpus spongiosum and glans. During this test, implantation of a telemetric pressure transducer allowed us to record ICP increases occurring simultaneously to erectile responses. These increases were characterized by brief suprasystolic peaks preceded by an infrasystolic plateau. Each type of reflex erectile response was accompanied by a characteristic profile of ICP increase. Participation of the corpora cavernosa was demonstrated, particularly during erections of the glans. In anaesthetised rats, electrical stimulation of the dorsal nerve of the penis induces an increase of intracavernous pressure which tends to reach blood pressure values. This erectile response of the corpora cavernosa is abolished by proximal section of the dorsal nerve of the penis, markedly decreased by section of the homolateral pelvic nerve, and abolished after bilateral section of the two pelvic nerves. Striated muscle paralysis does not abolish the erectile response. These data help to define the neurophysiology of the reflex erection. In particular, they provide a clearer explanation of the spinal integration of reflex erection.

Animals↗

Endothelial, haemostatic and haemorheological modifications in migraineurs.

Vasotropic, haemostatic and haemorheological parameters have been investigated in 17 patients suffering from migraine without aura in comparison with 11 sex and age matched healthy control subjects. NO metabolites (NO2- and NO3-), endothelin (ET-1), tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), fibrinogen, D-dimer, fibrinopeptide A, beta thromboglobulin (beta-TG), blood viscosity, plasma viscosity, haematocrit (Htc) and red blood cell (RBC) filterability index (FI) were determined during headache free periods. Migraineurs NO3- and ET-1 plasma levels, compared to control values, showed a significant decrease and increase respectively; fibrinogen, beta-TG and D-dimer appeared slightly lowered in migraineurs, while Htc remained in the normal limits; tPA, PAI-1 and FI were significantly reduced, while fibrinopeptide A, blood viscosity and plasma viscosity at a low shear rate (shr) exhibited a significant rise. Data obtained support the involvement of endothelial, haemostatic and haemorheological functions in the pathogenesis of migraine.

Adult↗