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G Italiano

Publications and source records attributed to G Italiano.

At least 19 recordsLinked to original sources

Changes of acute-phase proteins in streptozotocin-induced diabetic rats.

Quantitative and qualitative changes of serum proteins, apart from glycation, have not been sufficiently studied in streptozotocin-induced diabetic rats (D), the most common experimental model for diabetes. Thus, we decided to analyze the serum of diabetic rats by concanavalin A-blotting in comparison with rats with acute inflammation induced by fermented yeast (Y), in which characteristic alterations of serum proteins have been described. Two months after the streptozotocin treatment, the blood glucose levels were highly elevated (456+/-24 vs. 124+/-10 mg/dl, p<0.001, n=12), the body weight was significantly lower than normal (279+/-10 vs. 392+/-6 g, p<0.001, n=12), and serum proteins appeared to be highly glycated (p<0.001) when analyzed by the fructosamine assay, without any significant change in the total serum protein concentration. Analysis by concanavalin A-blotting, revealed a significant decrease of alpha1-inhibitor-3 (alpha1-I3, p<0.05) and an increase of the beta chain of haptoglobin (beta-Hp, p<0.05) in both D and Y rats (n=3) compared with control animals. However, acute inflammation caused a marked rise of two prominent acute phase proteins, alpha2-macroglobulin and hemopexin, which did not change appreciably in diabetic rats. Further work will be necessary to evaluate the physiopathological significance of these phenomena which could result from changes of both concentration and glycosylation of the aforementioned proteins.

Acute-Phase Proteins↗

Functional response of cavernosal tissue to distension.

We studied rabbit isolated erectile tissue responses to changes in preload and to active tension development with norepinephrine. The effects of antagonists of endothelin-1, prostaglandins E2 and F2alpha and of nitric oxide were also tested on normal and de-endothelialized preparations. Tissue distension was found to elicit spontaneous rhythmic contractions. Increase in preload diminished the latency of the spontaneous activity and augmented the developed force. Active tension development and the inhibitor of the Na+,K+ pump, ouabain, opposed the spontaneous activity. A marked reduction in the resting tension with abolition of the spontaneous activity was observed on normal, but not on de-endothelialized tissues, following the addition of the specific prostaglandin E2 and F2alpha receptor antagonist, SC-19220. At 3 x 10(-4) M, the highest concentration used, the endothelin-A receptor antagonist BQ-123 failed to change the pattern of the spontaneous activity and the resting tension of normal tissues. The nitric oxide synthesis inhibitor, L-NAME, did not produce reliable effects. These findings point to a causal relation between cavernosal tissue distension and phasic and tonic contractions. Phasic contractions appear to be elicited by smooth muscle cells through the enzyme Na+,K+-ATPase. Increase in the resting tone could be mediated, at least in part, by the endothelium, through the release of prostaglandins E2 and/or F2alpha but not of endothelins. We discuss the hypothesis that, in cavernosal tissue, mechanotransduction of distension to contractile responses is an important determinant of detumescence.

Acetylcholine↗

Guiding spontaneous tissue regeneration for urethral reconstruction: long-term studies in the rabbit.

We designed long-term in vivo experiments to study rabbit urethral regeneration and remodelling over a hyaluronan biodegradable prosthesis. Seven months after the resection of a 1.5-cm-long tract of the urethra and its substitution with the prosthesis, radiological analysis showed the disappearance of the implant and the re-establishment of urethral continuity along the transmural defect. The regenerated tissue remodelled around the implant and exhibited good distensibility under pressure. Histological evaluation showed that the neo-urethra was lined with transitional epithelium and the stroma contained abundant elastic fibres. An examination of the pattern of the major cytoskeletal and cytocontractile proteins of smooth muscle cells and fibroblasts was able to distinguish fibroblasts from smooth muscle cells and myofibroblasts in the neo-urethra. These experiments provide evidence for the potential, successful use of biocompatible/bioresorbable devices for reconstructive surgery of the urethra.

Actins↗

Reconstructive surgery of the urethra: a pilot study in the rabbit on the use of hyaluronan benzyl ester (Hyaff-11) biodegradable grafts.

We investigated the outcome of reconstructive surgery of the urethra through guides composed of a novel biodegradable and highly biocompatible polymer, Hyaff-11. A tract of about 1.5 cm of the rabbit pendulous urethra was totally resected and replaced by a Hyaff-11 tubular graft. Eleven animals were analysed at each of the time points ranging from 7 days to 4 weeks following surgery. Histological and radiological evaluation showed a satisfactory remodelling of the neo-urethra around the implant. The regenerated connective tissue connected both urethral stumps within the first 7 days. On postoperative week 3, the Hyaff-11 guide had disappeared. At the 4-week time point the retrograde urethrogram showed a good distensibility of the neourethra. The regenerated stroma consisted of fibroblastic cells, and collagenous and elastic fibres. The neo-epithelium was pluristratified and exhibited cells of the cuboidal type.

Animals↗

Characterization of in vitro relaxant mechanisms in erectile tissue from rabbits of different ages.

In the present study we investigated the in vitro relaxant response of erectile tissue obtained from rabbits of different ages (3, 7 and 24 months) in order to detect the progression with age of cavernosal activity in response to substances acting via endothelium-dependent or -independent mechanisms. Noradrenaline induced a concentration-dependent contraction (0.1 microM-3 mM), with an increase in the contractility in the 24-month-old group. Acetylcholine produced a concentration-dependent relaxant effect in the three age groups, with a reduction of the maximal relaxant effect in older animals. ATP (10 microM-1 mM) and adenosine (10 microM-1 mM) induced a concentration-dependent relaxant effect that was higher in the older group. The presence of the NO2-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) (0.1 mM) or of the P2-purinoceptor antagonist suramin did not affect ATP relaxation. Relaxation induced by sodium nitrite and nifedipine was reduced in older animals. In conclusion, aging selectively alters the in vitro responsiveness of rabbit erectile tissue. Purinergic system remains more active despite a decrease in the maximal endothelial cholinergic activity and the direct smooth muscle relaxant component.

Acetylcholine↗

Chronic treatment with cyclosporine A in New Zealand rabbit: aortic and erectile tissue alterations.

Transplanted patients frequently present erectile impotence. In order to test any interference by cyclosporine A (CsA), which is commonly used in the post-transplantation management, we investigated the in vitro contractile and relaxant responses of corpus cavernosum and aorta from rabbits chronically treated with CsA. Male New Zealand White rabbits 6 months of age were treated with CsA (25 mg/kg per day s.c.) or solvent (corn oil) for 3 weeks. Descending thoracic aorta and erectile tissue were studied in vitro at the end of treatment. Isometric tension was recorded. In thoracic aorta, noradrenaline (0.1-30 mM) induced a concentration-dependent contraction with no difference between the two groups. Acetylcholine (30 nM-3 mM) produced relaxation (52 +/- 4% at 1 mM) that was significantly reduced in comparison to controls (67 +/- 4%, P < 0.05). ATP (3-10 mM) relaxation was not significantly different (maximal 78 +/- 10% and 62 +/- 12% in CsA-treated and controls). The relaxation produced by sodium nitrite was reduced in CsA-treated rabbits (at 10 mM and 0.1 mM concentrations). In erectile tissue, no significant variation in the response of isolated erectile tissue to the above drugs was observed between CsA-treated and control animals. These data indicate that chronic treatment with CsA in rabbits, despite alteration of the in vitro response of thoracic aorta, does not directly influence the function of penile tissue with relaxants.

Animals↗

Physiological aging and penile erectile function: a study in the rat.

Erectile function of adult (8-month-old) and aged (27-month-old) rats was investigated by in vivo and in vitro assays. Reflexogenic tonic erections were evoked in vivo by electrostimulation of the dorsal nerve of the penis. Aged rats developed tendentially low intracavernosal pressures, and the kinetics of erection and detumescence were significantly lower than in adult animals. The erectile tissue isolated from aged rats exhibited poor response to papaverine. When precontracted with norepinephrine, aged tissues required a 3-fold increase of papaverine concentration to full relaxation. Functional measurements were coupled with morphological analysis of elastic fibres of the tunica albuginea. Light microscopy showed degenerative signs of elastic fibres of aged rat specimens. Taken together, the present findings show that physiological aging is associated with penile tissue stiffness and abnormal corporal compliance.

Aging↗

Effects of prostaglandin E1, and papaverine on non-neurogenic and neurogenic contraction of the isolated rabbit erectile tissue.

Experiments were performed to get further insights into the erectogenic mechanism of prostaglandin E1 (PGE1), which was compared to that of papaverine (PAP). PGE1 and PAP were effective in abolishing the contraction induced by N-ethylmaleimide (NEM), an adenylate cyclase blocker. However, preincubation with PGE1 but not with PAP markedly attenuated the amplitude of adrenergic nerve mediated contraction following prolonged electrical field stimulation. Preincubation with PGE1 was ineffective in counteracting the increase in tension due to exogenous norepinephrine. These data together with previous studies corroborate the hypothesis that in the presence of PGE1 a dual erectogenic mechanism takes place in modulating the cyclic-adenosine-monophosphate metabolism of the cavernous smooth muscle cell as well as the release of norepinephrine from the sympathetic terminal.

Alprostadil↗

Bladder function in the aged rat: a functional and morphological study.

This study was designed to characterize urinary bladder function in the aged rat (27 months of age). For comparative purposes, two different control groups were included into the experimental protocol: normal 6-month old and hyperdiuretic 6-month old rats. Increased threshold volume for micturition and increased bladder mass were found in both aged and hyperdiuretic rats. No difference in the amplitude of micturition contractions was detected between groups. In the aged rat, but not in the hyperdiuretic one, augmented threshold volume and bladder mass were associated with increased intravesical pressure at micturition and structural changes of intramural bladder innervation. When activated, the vesicovesical reflex did not show any change in terms of rate of isovolumetric contractions. In the aged rat, altered sensory information on the state of maximum fullness seems to play an important role in determining abnormal cystometric findings.

Age Factors↗

A simplified in vitro preparation of the corpus cavernosum as a tool for investigating erectile pharmacology in the rat.

This work describes a simple technique for the assessment of corpus cavernosum function in a species, the rat, representing a convenient model for basic research. We obtained measurable and reproducible responses to different pharmacological agents as well as to electrical field stimulation. In view of the present results we conclude that isolation of the erectile tissue together with the septum may constitute a valuable experimental tool for investigating both local erectile mechanisms and the action of drugs, in the rat corpus cavernosum. Data obtained in the presence of N-nitro-L-arginine and methylene blue further reinforce the concept that nitric oxide may be involved in the process of erection in the rats as well as in other animal species.

Animals↗

Electrical stimulation of the dorsal nerve of the penis evokes reflex tonic erections of the penile body and reflex ejaculatory responses in the spinal rat.

An animal model using the spinal rat was characterized. Electrical stimulation of the dorsal nerve of the penis elicited reflex tonic erections of the penile body and reflex bulbospongiosus muscle activity, flips and ejaculations. The tonic erections of the penile body are independent from contractions of the bulbospongiosus muscle and appear to be the result of a neurovascular process. Our observations suggest that reflex bulbospongiosus muscle activity, flips and ejaculations are a single complex reflex response, which we define as reflex ejaculatory response. Two parameters predicted the occurrence and type of reflex response. The visualization of bulbospongiosus muscle activity during surgical isolation of the dorsal nerve of the penis was sufficient to anticipate the elicitability of reflex ejaculatory responses. The latter, together with a systemic systolic pressure > or = 73 mmHg., warranted the elicitability of reflex tonic erections. The similarities found in the physiology of rat tonic penile body erections and of human erections make this model promising for further elucidation of sexual function. Moreover, the present model may prove useful for the investigation of neurogenic erectile dysfunction, and of neurogenic ejaculatory disorders.

Animals↗

Ultrastructural analysis of the cavernous and dorsal penile nerves in experimental diabetes.

The present study was designed to investigate whether experimental diabetes determines structural changes in peripheral nerves involved in reflexogenic erection, namely the cavernous and the dorsal nerve of the penis. Myelinated axons were examined in the dorsal nerve of the penis from rats with streptozotocin-induced diabetes (3- and 6-month duration). Morphometric analysis disclosed a significant decrease of myelinated fibre size most likely due to a progressive axonal atrophy. In addition, morphological analysis revealed diffuse accumulation of glycogen within axons, lipid droplets in Schwann cells and pronounced sequestration of axoplasm by adaxonal Schwann cell processes. These signs were particularly prominent in 6-month-diabetic rats. Myelinated and unmyelinated axons of the cavernous nerve were analysed in 6-month-diabetic animals. No substantial ultrastructural abnormalities were found in the cavernous nerves. These results suggest that in experimental diabetes regionally specific structural changes occur in neuronal pathways subserving erectile function.

Animals↗

Effect of streptozotocin-induced diabetes on electrically evoked erection in the rat.

This study was designed to investigate whether experimental diabetes in rats could functionally affect reflexogenic erection. Erection was elicited by means of electrical stimulation of the dorsal nerves of the penis and recorded as intracorporeal pressure. Rats were examined 1, 3 and 6 months after diabetes induction by streptozotocin. Three and 6 month diabetes caused a significant decrease of latency for erection and a slower phase of detumescence when compared to age-matched controls. In addition, a trend for a lower developed intracorporeal pressure was present in the 6 month diabetes group. Our results indicate that experimental diabetes is associated with alterations of reflexogenic erection.

Animals↗

Functional responses of hindlimb circulation in aged normal and WHHL rabbits.

Normal New Zealand and Watanabe heritable hyperlipidemic (WHHL) rabbits, about 24 months old, were prepared, under anaesthesia, for recording blood pressure and hindlimb blood flow. Changes in hindlimb vascular resistance were measured after local intra-arterial bolus injection of increasing doses of acetylcholine, bradykinin, serotonin, sodium nitroprusside and phenylephrine. In WHHL rabbits basal hindlimb blood flow was reduced (from 22.6 +/- 3.0 to 12.5 +/- 1.8 ml/min; P less than 0.05) and hindlimb vascular resistance was increased (from 4.6 +/- 0.5 to 8.2 +/- 1.5 mmHg/ml per min; P less than 0.05). No difference was observed in response to acetylcholine, serotonin, sodium nitroprusside and phenylephrine. The only marked alteration found in WHHL rabbits was a clear deficit to bradykinin stimulation. Morphological analysis, using scanning and transmission electron microscopy, indicated a clear damage of the femoral artery, like the presence of atherosclerotic plaques, and an abnormal distribution of patent microvessels in the WHHL muscles of the leg. Peripheral circulation in WHHL rabbits shows some peculiar features, like increased basal vascular resistance and a selective impairment of bradykinin responses. Together with these abnormalities, it seems that responses to various other dilating or contracting agents are normal, suggesting that in this interesting animal model of atherosclerosis the alterations are more specific than in other models.

Acetylcholine↗

Inner ester derivatives of gangliosides protect autonomic nerves of alloxan-diabetic rats against Na+, K(+)-ATPase activity defects.

Bovine brain gangliosides have been shown to prevent decay in Na+,K(+)-ATPase activity in sciatic and optic nerves of alloxan- and streptozotocin-diabetic rats. In the search for a drug with greater bioavailability and increased incorporation into neural tissue, ganglioside inner ester derivatives (AGF1) were recently developed. We evaluated the effect of AGF1 treatment on Na+,K(+)-ATPase activity in homogenates of vagus nerve from alloxan-diabetic rats (100 mg/kg s.c.). Animals were treated with AGF1: 10 mg/kg 6 days/week i.p., or 30 mg/kg biweekly i.p. Treatment began 10 d post-alloxan and continued for 8 consecutive weeks. Normal age- and sex-matched rats were used as controls. Alloxan intoxication produced a 39% decrease in Na+,K(+)-ATPase activity of the vagus nerve, which was completely restored (96-97% recovery) by both AGF1 regimes. Results suggest that ganglioside inner ester derivatives may be used in the clinical setting for the management of diabetic autonomic neuropathy.

Animals↗

Cystometric changes in alloxan diabetic rats: evidence for functional and structural correlates of diabetic autonomic neuropathy.

Autonomic neuropathy and urinary bladder function were compared in Sprague-Dawley rats with alloxan-diabetes of 3 months duration, rats fed sucrose for 8 weeks, and rats examined 8 weeks after pelvic nerve surgical axotomy; normal age-matched rats were used as controls. All experimental interventions induced bladder hypertrophy with increased bladder weight. In diabetic and sucrose-fed animals, water intake and urinary output increased. Cystometric recordings of normal rats in vivo showed rhythmic contractions (1.25 +/- 0.25 contr/min) with threshold volume for micturition reflex at 0.51 +/- 0.04 ml. In diabetic rats, bladder contractions were irregular and of lower frequency (0.60 +/- 0.04 contr/min), while threshold volume was significantly higher (1.00 +/- 0.11 ml). Bladder contractions were normal in sucrose-fed animals, though threshold volume was markedly augmented (1.27 +/- 0.19 ml). Pelvic nerve surgical ablation abolished micturition reflex. In bladder strips excised post-mortem, contractile response to field stimulation was reduced in diabetic rats compared to control and sucrose-fed animals. Morphological examination of pelvic and hypogastric nerves revealed abnormalities characteristic of diabetic neuropathy only in diabetic rats. These data suggest that in alloxan-induced diabetes the decrease in the rate of bladder contraction is the result of autonomic neuropathy; while bladder hypertrophy in sucrose-fed rats appears to be an organ adaptation to hyperdiuresis.

Alloxan↗