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Biomedical subjects

A Giraldi

Publications and source records attributed to A Giraldi.

At least 19 recordsLinked to original sources
PubMed2002

Morphological and functional characterization of a rat vaginal smooth muscle sphincter.

The aim of the present study was to gain information about adrenergic-, cholinergic- and non-adrenergic, non-cholinergic (NANC)- transmitter systems/mediators in the rat vagina, and to characterize its smooth muscles functionally. Tissue sections from vagina of Sprague Dawley rats were immunolabelled with antibodies against protein gene product 9.5 (PGP), synaptophysin (Syn), tyrosine hydroxylase (TH), vesicular acetylcholine transporter (VAChT), neuropeptide Y (NPY), nitric oxide synthase (NOS), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Circularly cut vaginal smooth muscle preparations from the distal vagina were studied in organ baths. In the paravaginal tissue, a large number of PGP-, NOS-, TH-, VIP-immunoreactive (IR) and few CGRP-IR nerve trunks were observed, giving off branches to the smooth muscle wall. The smooth muscle wall was supplied by a large number of PGP-, Syn-, VAChT-, NPY-, NOS- and TH- IR nerve terminals, whilst only a moderate to few numbers of CGRP-, VIP- and PACAP-IR terminals were identified. Especially the distal part of the vaginal wall, where the circularly running smooth muscle was thickened into a distinct sphincter structure, was very richly innervated, predominantly by PGP- and NOS-IR terminals. Below and within the basal parts of the epithelium in the distal half of the vagina, a large number of PGP- and few NOS- and PACAP-IR varicose terminals were observed. The vaginal arteries were encircled by plexuses of nerve terminals. A large number of these were PGP-, Syn-, VAChT-, NOS-, TH-, NPY- and VIP-IR, and few were CGRP- and PACAP-IR. In isolated preparations of the distal vagina, electrical field stimulation (EFS) caused frequency-dependent contractions, which were reduced by sildenafil, tetrodotoxin (TTX) and phentolamine. In preparations contracted by norepinephrine (NA), EFS produced frequency-dependent relaxations. Pretreatment with the NOS-inhibitor N(G)-nitro-L-arginine, TTX, or the inhibitor of soluble guanylate cyclase, ODQ, abolished the EFS relaxations. In NE precontracted preparations, cumulative addition of sildenafil caused concentration-dependent relaxation. Carbachol contracted the strips concentration-dependently from baseline. It can be concluded that the distal part of the rat vagina forms a distinct smooth muscle sphincter, which is richly innervated by adrenergic, cholinergic and NANC nerves. The present studies suggest that in the rat the L-arginine/NO-system not only plays an important role in the regulation of vaginal smooth muscle tone, but also affects blood flow, and may have sensory functions.

Acetylcholinesterase↗
PubMed2002

Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.

PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole cell potassium currents that were blocked by glibenclamide (10 microM.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

Adenosine Triphosphate↗
PubMed2001

Effects of diabetes on neurotransmission in rat vaginal smooth muscle.

The aim of this work was to characterize the effect of experimental diabetes on neurotransmission in rat vagina. Female Sprague-Dawley rats were divided into two groups: non-diabetic controls (NDM, n=38) and diabetics (DM, n=38). DM was produced by intraperitoneal injection of streptozotocin. Eight weeks later the animals were killed, the distal part of the vagina was removed, and smooth muscle strips were prepared for functional organ bath experiments and for measurement of nitric oxide synthase (NOS) activity. In DM preparations, the EC(50) value for noradrenaline (NA) was significantly increased (P<0.05) and the maximal contractile response decreased (P=0.001). In preparations precontracted with NA, the NO donor SNAP and calcitonin gene-related peptide (CGRP) caused concentration-dependent relaxations, which were significantly decreased (P<0.001) in the DM group. Electrical stimulation of nerves (EFS) caused frequency-dependent contractions, which were significantly lower in DM than in NDM strips (P<0.001). SNAP and CGRP concentration-dependently inhibited EFS evoked contractions in both NDM and DM preparations. The inhibition was significantly lower (P<0.05) in the DM group. In NDM preparations precontracted with NA, EFS evoked frequency-dependent relaxations; such relaxations were inhibited or reduced in DM. Treatment with the NOS inhibitor, L-NOARG 0.1 mM, abolished relaxations in all preparations or produced contraction in DM preparations. Calcium-dependent NOS activity was not significantly different in the DM and NDM groups. However, the DM animals showed a small but significant increase in calcium-independent NOS-activity (P<0.05). Diabetes interferes with adrenergic-, cholinergic- and NANC-neurotransmitter mechanisms in the smooth muscle of the rat vagina. The changes in the nitrergic neurotransmission are not due to reduction in NOS-activity, but seem to be due to interference with later steps in the L-arginine/NO/guanylate cyclase/cGMP system.

Animals↗
PubMed2000

Abanoquil, a new alpha-1 adrenoceptor antagonist. In vitro and in vivo effect on erectile tissue.

Using an organ bath model with porcine cavernosal tissue strips and an in vivo monkey model we demonstrated that abanoquil, a novel alpha adrenoceptor antagonist, is able to relax contracted tissue strips and induce erectile response when injected intracorporally. The erectile response in the monkeys was not dose-related and compared to the effect of papaverine injections, abanoquil induced a lower level of tumescence and rigidity. Hence, abanoquil might be useful as a facilitator of erection in the pharmacological treatment of erectile dysfunction.

Adrenergic alpha-Antagonists↗
PubMed2000

Abanoquil, a new alpha-1 adrenoceptor antagonist. In vitro and in vivo effect on erectile tissue.

Using an organ bath model with porcine cavernosal tissue strips and an in vivo monkey model we demonstrated that abanoquil, a novel alpha adrenoceptor antagonist, is able to relax contracted tissue strips and induce erectile response when injected intracorporally. The erectile response in the monkeys was not dose-related and compared to the effect of papaverine injections, abanoquil induced a lower level of tumescence and rigidity. Hence, abanoquil might be useful as a facilitator of erection in the pharmacological treatment of erectile dysfunction. International Journal of Impotence Research (2000) 12, Suppl 1, S37-S40

Journal Article↗
PubMed1998

Molecular studies of human connexin 43 (Cx43) expression in isolated corporal tissue strips and cultured corporal smooth muscle cells.

Intercellular communication plays an important role in erectile function. The goal of this study, therefore, was two-fold. Firstly, to determine if cultured corporal smooth muscle cells provide a valid model system for evaluating the role of junctional communication to erectile physiology, and secondly, to explore the possibility that there may be age-related alterations in Cx43 mRNA expression. Human corpus cavernosum tissue was obtained from 31 patients with a mean age of 58 (range 27-89), while cell cultures were developed from 21 distinct patients with a mean age of 57 (range 26-59). Northern blots revealed that mRNA for Cx43 was expressed at detectable levels in all samples examined. It migrated as a transcript with an apparent size of 3.1 Kb. Western blots revealed the presence of multiple bands of Cx43 protein in both tissues and cells. However, Cx43 protein in tissue predominantly migrated as a 45 kDa band, while the Cx43 from cultured cells predominantly migrated as 41 kDa band. Cx43 mRNA expression was similarly heterogeneous in both frozen tissues and cultured cells. An approximately 3-5-fold increase in Cx43 mRNA levels was observed in cultured cells relative to frozen tissue, but the expression of Cx43 mRNA was not further altered upon passaging (p1-5). When Cx43 mRNA levels were normalized, and expressed as a ratio of the Cx43/beta-tubulin mRNA, there was a significant negative correlation between patient age and Cx43 levels on frozen tissues, but not on cultured cells. We conclude that: (1) There is similar heterogeneity/variability in Cx43 mRNA levels in frozen tissues and cultured cells derived from human corpus cavernosum. (2) That the expression of Cx43 mRNA in cultured cells is sufficiently stable, and similar to, expression levels in tissue as to provide a valid and physiologically relevant model system for further studying the role(s) of Cx43 in the regulation of penile erection. (3) There is a statistically significant, albeit modest, negative correlation between the Cx43/beta-tubulin ratio and patient age in frozen corporal tissue strips, but not on cultured corporal smooth muscle cells. Such observations provide further evidence for the plasticity of intercellular communication in the erectile process. Moreover, the similarities in the apparent regulation of Cx43 mRNA levels and that of the putative 'housekeeping' gene beta-tubulin, may suggest that Cx43 is constitutively synthesized in this tissue.

Adult↗
PubMed1998

Endothelin-1 as a putative modulator of gene expression and cellular physiology in cultured human corporal smooth muscle cells.

PURPOSE: Increases in cytosolic calcium levels trigger smooth muscle contraction while nuclear calcium increases are thought to regulate gene expression. Endothelin-1 (ET-1) affects both. The goal of these studies was to further investigate the importance of ET-1 to corporal physiology by examining its actions on proliferation and immediate early gene (IEG) expression in cultured human corporal smooth muscle cells. MATERIALS & METHODS: Early passage (1-3) smooth muscle cells were grown in culture and exposed to either phenylephrine (PE) or ET-1 in the absence and presence of serum, the ET(A) or ET(B) selective antagonist BQ123 or IRL1038, or the L-type Ca2+ channel blocker, verapamil. Cell proliferation was assessed with a hemocytometer. The effects of ET-1 on c-myc and c-fos were evaluated using Northern blot analysis. Parametric or nonparametric statistics were used as appropriate. RESULTS: Addition of ET-1 (100 nM) to serum-starved cultured corporal smooth muscle cells was associated with a nearly 2-fold increase in cell number, as well as 2 to 6-fold increases in c-myc and c-fos levels. Cellular proliferation was inhibited by ET(A)- or ET(B)-receptor subtype blockade with BQ123 (1 microM) or IRL1038 (1 microM), respectively, or blockade of Ca2+ channels with verapamil (10 microM). PE (3 microM) had no detectable effect on smooth muscle proliferation. CONCLUSIONS: Cell proliferation was mediated by activation of the ET(A) and ET(B) receptor subtypes, dependent on transmembrane Ca2+ flux, and correlated with significant increases in c-myc and c-fos mRNA levels. These studies extend previous observations to indicate the potential pleotropic actions of this peptide in the regulation of human corporal smooth muscle physiology in vivo.

Adult↗
PubMed1994

Characterization of cyclic AMP accumulation in cultured human corpus cavernosum smooth muscle cells.

Intracavernous pharmacotherapy relies heavily on the use of vasoactive agents which act by increasing intracellular cAMP levels in human corpus cavernosum smooth muscle. Yet little is known about the cAMP generating system in this tissue, and how it may affect observed patient variability. Thus, the goal of these studies was to better characterize the biochemistry of cAMP formation in human corpus cavernosum smooth muscle, and thus provide more insight into the mechanisms of corporal smooth muscle relaxation in vivo. We studied both receptor and nonreceptor mediated increases in cAMP formation in short-term cultures of human corpus cavernosum smooth muscle cells. Both isoproterenol (ISO) and prostaglandin E1 (PGE1) produced concentration-dependent increases in cAMP, but histamine, serotonin and vasoactive intestinal polypeptide did not. Forskolin, a relatively specific activator of adenylate cyclase, was also a potent stimulant of cAMP formation in these cells. Moreover, there was a direct correlation between the degree of forskolin-induced cAMP accumulation in cultured corporal smooth muscle cells and the magnitude of the forskolin-induced relaxation response of precontracted isolated corporal smooth muscle strips. Prostaglandin E1 and ISO concentration response curves (CRCs) were then assayed in the absence and presence of subthreshold forskolin (0.1 microM.). In the presence of forskolin, the calculated maximal PGE1-induced cAMP accumulation (Emax) was significantly greater than that elicited by PGE1 alone, ISO alone, or ISO + forskolin (p < or = 0.02). In addition, a fixed molar ratio (FMR) (PGE1:ISO) protocol was used to demonstrate that both 80:20 and 70:30 FMRs (but not 95:5 or 90:10), were associated with significantly greater cAMP Emax values than that observed for PGE1 alone (p < or = 0.01). These data provide direct evidence that the degree of cAMP formation in cultured corporal smooth muscle cells is strongly correlated with the magnitude of relaxation of isolated corporal smooth muscle strips. In addition, since simultaneous activation of distinct components of the cAMP generating system produces significant increases in maximal intracellular cAMP accumulation, this suggests that such drug combinations may also augment corporal smooth muscle relaxation in vitro and in vivo.

Alprostadil↗
PubMed1992

Staging of malignant tumours of the foot.

Tumours of the foot in general, and malignant tumours in particular, are extremely rare. In the absence of a large series it is necessary to resort to surgery based on "principles" and not on experience or on data drawn from retrospective clinical studies. Enneking's "Surgical Staging System" (S.S.S) is a method of staging musculo-skeletal tumours which has been universally adopted-for several years and which is based, as already known, on the concept of anatomo-surgical "compartments". In the particular case of the foot, the S.S.S. suggests the surgical criteria specific to each anatomical region. The authors illustrate the principles with some examples taken from their experience, evaluating the surgical, oncological and functional aspects.

Aged↗
PubMed1991

Diaphyseal and metaphyseal hemiresection with autograft reconstruction in the treatment of lowgrade tumors of the long bones.

The authors discuss seven cases of parosteal tumors treated conservatively by diaphyseal and metaphyseal hemiresection with cortical autograft reconstruction. This treatment yielded excellent clinical and functional results without having to resort to resection and arthrodesis or prosthetic replacement. The slow growth and low malignancy of these tumors make the use of this technique possible even at the risk of local recurrence, which, if discovered early, can still be treated by further conservative procedures.

Adolescent↗
PubMed1990

Effects of pinacidil upon penile erectile tissue, in vitro and in vivo.

The effect of pinacidil, a new antihypertensive vasodilator, was studied in vitro upon human and porcine Corpus cavernosum and in vivo upon simian Corpus cavernosum. In vitro, pinacidil incubation (10(-5)-10(-3) M) was found to induce a concentration-dependent inhibition of the tissue response to norepinephrine (NE) and high potassium (K+). Likewise a concentration-related relaxation of the tissue, precontracted with either NE or K+, was seen using pinacidil 10(-5)-10(-3) M. Depending on the concentration applied, spontaneous activity as well as tone and amplitude of the contractions were reduced until total relaxation of the tissue was obtained with a pinacidil incubation of 10(-3) M. In vivo, 5 mg pinacidil in 0.3 ml solution was injected intracavernosally in 17 monkeys. Sixteen monkeys developed tumescence and 10, rigidity of the penis as well. Only one of 5 showed a decrease in the systemic blood pressure. Pinacidil might be of clinical interest as an agent facilitating erection when given intravernosally.

Animals↗
PubMed1990

Oxytocin and the initiation of parturition. A review.

Oxytocin (OT) binds to specific receptors of myometrial cells, inducing and increasing myometrial contractions. During pregnancy and especially close to term, an increase in the myometrial OT-receptor concentration is found, leading to an increased sensitivity of the myometrium towards circulating OT. The factors determining the receptor level are not completely understood, but may include the level of steroids, OT- and oestrogenreceptors. Because of the increased sensitivity, only a small increase in the maternal OT blood-level is necessary to induce myometrial contractions at term. The level of maternal plasma OT does not change significantly throughout pregnancy. The fetus is found to secrete considerable amounts of OT during the first stage of labour, which reaches the myometrium in spite of the high level of oxytocinase in placenta. At the second stage of labour the distension of the lower birth canal might cause release of OT from the maternal neurohypophysis into the blood, increasing the myometrial contractions. This mechanism is observed in animals, but not established in the human.

Amino Acid Sequence↗
PubMed1984

Aneurysmal bone cyst of the patella.

Aneurysmal bone cysts of the patella are extremely rare. Only 4 cases have been reported in the literature. The authors add a fifth case which came under their observation.

Adult↗
PubMed1982

[Incidence of osteodystrophy after transplantation: basic outlines and orthopedic problems].

The generic term "Renal Osteodystrophy" is used to denote a complex of skeletal and metabolic impairments found in nephropathic patients. Neither dialytic treatment nor transplant is always capable of limiting the worsening evolution; transplantation, on the contrary, while it does not in many cases bring the phospho-calcic metabolism back to full normality, introduces new elements of imbalance arising as a result of the inevitable immunosuppressive therapy. After outlining the main post-transplant metabolic problems, the Authors discuss the manifestations of orthopaedic interest, in particular the most severe complication, i.e. aseptic necrosis.

Cholecalciferol↗
PubMed1982

[Epiphyseal chondroblastoma: natural history and clinico-radiographic aspects].

The authors intend to supply a wide and valid framing of the present knowledges about epiphysis blastoma, excluding the therapeutical problems. After a short historical note, they illustrate the elements of natural history, search into the radiologic and anatomo-pathologic aspects of such neoplasia with the differential diagnoses involved, and, at last, discuss the histogenetic hypotheses. The analysis of the classic and unusual evolutive aspects is set forth as a conclusion of the work.

Adolescent↗
PubMed1982

[Evolution of renal osteodystrophy after renal transplant: basic elements and orthopedic problems].

The generic term "Renal Osteodystrophy" is used to denote a complex of skeletal and metabolic impairments found in nephropathic patients. Neither dialytic treatment nor transplant is always capable of limiting the worsening evolution; transplantation, on the contrary, while it does not in many cases bring the phospho-calcic metabolism back to full normality, introduced new elements of imbalance arising as a result of the inevitable immunosuppressive therapy. After outlining the main post-transplant metabolic problems, the Authors discuss the manifestations of orthopaedic interest, in particular the most severe complication, i.e. aseptic necrosis.

Calcium↗