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Biomedical subjects

V Cuomo

Publications and source records attributed to V Cuomo.

At least 55 records · Page 3Linked to original sources

Role of polysialic acid in peripheral myelinated axons.

Polysialic acid (PSA), generally lost from the vertebrate nervous system during maturation, may regulate developmental differences in axon growth, bundling, and sprouting. Changes in polysialic levels on the axon surface seem to be involved during development in establishing normal pattern of muscle innervation. Besides the well-established role of PSA as a regulator of cell-cell interactions during development, PSA expression in myelinated axons may be related to reparative events in response to chemically induced injuries. Histochemical staining method using lectins with well-characterized binding specificities shows that glycoconjugates of the node of Ranvier undergo a rearrangement during exposure to 2,5-hexanedione, known to induce a peripheral neuropathy characterized by giant axonal swelling and retrograde demyelination. In particular, neutral glycoproteins with terminal galactose are replaced by sialoglycoproteins, consistent with the proposed role of PSA as a regulator of axonal behaviour during regeneration.

Animals↗

Perinatal cocaine reduces responsiveness to cocaine and causes alterations in exploratory behavior and visual discrimination in young-adult rats.

Lister hooded female rats were exposed to either saline or cocaine (20 mg/kg s.c.) from gestational day 10 every other day until weaning (postnatal day 25). The effects of maternal cocaine exposure on novelty-induced exploration and on spontaneous and cocaine-induced motor activity were evaluated in young-adult male offspring (4 weeks after weaning). Rats exposed to cocaine during development spent less time exploring two novel objects. Lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and familiar object were also found in cocaine exposed offspring. Moreover, maternal cocaine treatment did not affect spontaneous motor activity (active time, average speed and rearing) in rats subjected to an open field test. Furthermore, perinatal exposure to cocaine significantly attenuated acute cocaine (15 mg/kg i.p.)-induced hyperactivity. These data indicate that developmental exposure to cocaine, at dose levels below those producing gross malformations and/or overt signs of neurotoxicity, causes behavioral changes characterized by an altered responsiveness to environmental and pharmacological challenges.

Animals↗

Prenatal exposure to carbon monoxide and vascular responsiveness of rat resistance vessels.

The aim of the present study was to investigate the influence of prenatal exposure to carbon monoxide (CO) on vascular reactivity of rat resistance vessels, in different stages of neurogenesis. Both prenatally CO-exposed and control male Wistar pups (5-7, 9-11, 14-16, 20-22 days) were tested vs respective 60 day adult rats. The results showed that: (i) at 5-7 days of age, TTX caused a more marked inhibition of perivascular nerve stimulation (PNS)-evoked vasoconstriction in CO-exposed animals with respect to controls; (ii) the NO-related relaxant effect by ACh in CO-exposed group appeared earlier (5-7 days) than in control group (9-11 days); (iii) the contractile response evoked by ACh on resting tone disappeared earlier (after 14-16 days) than in control group (after 20-22 days). These observations suggested that CO-exposure might induce changes in nerve electrophysiological properties and might cause a precocious maturation of the NO-related enzymatic mechanism implicated in ACh-relaxation.

Acetylcholine↗

Sigma receptor modulation of noradrenergic-stimulated pineal melatonin biosynthesis in rats.

Because sigma receptors are richly concentrated in the rat pineal gland, the present study was performed to investigate their possible role in the modulation of melatonin production. To this purpose, we assessed in vivo the effects of the sigma-receptor ligands 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine on the rat pineal gland activity during either the daytime or the nighttime. Compared with vehicle, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine potentiated the enhancement of N-acetyltransferase activity and pineal melatonin content induced by isoproterenol administration during the daytime, whereas they did not affect the diurnal basal biosynthetic activity of the gland. Conversely, at night, 1,3-di(2-tolyl)guanidine and (+)-N-allylnormetazocine enhanced significantly the physiological increases in both pineal N-acetyltransferase activity and melatonin levels. This enhancement was prevented by pretreatment with rimcazole, a specific sigma-receptor antagonist. These findings suggest that, in rats, the activation of pineal sigma-receptor sites does not affect the biosynthetic activity of the pineal gland during daytime, whereas it potentiates the production of melatonin when the gland is noradrenergically stimulated either by isoproterenol administration or by the endogenously released norepinephrine at nighttime.

Animals↗

Appropriate end points for the characterization of behavioral changes in developmental toxicology.

The present paper is devoted to second- and higher-tier test methods for the characterization of behavioral changes produced in rodents by exposure to noxious agents during development. The paper analyzes a series of end points that are informative about specific processes and underlying regulatory mechanisms but require greater technical sophistication and larger investments than first-tier end points. This applies to ultrasonic emissions in successive postnatal periods; to mother-pup interactions, including appropriate cross-fostering controls; to social (including sexual) interaction tests from the infantile to the young adult stage; and to a variety of conditioning and learning tests using both positive and negative reinforcement.

Animals↗

Developmental neurotoxicity of carbon monoxide.

The results of recent studies dealing with behavioral and electrophysiological dysfunctions induced in rat offspring by prenatal exposure to relatively mild CO concentrations (75 and 150 ppm) have been reviewed in the present paper. In particular, gestational exposure to CO produced the following behavioral changes: (i) reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest; (ii) decrease in ultrasonic responsiveness to a challenge dose of diazepam; (iii) alterations in the acquisition of an active avoidance task. The electrophysiological changes induced by prenatal CO in peripheral nervous system are as follows: (i) increase in time constants of sodium current inactivation; (ii) increase in the percentage of the maximum number of activatable sodium channels at the normal resting potential; (iii) negative shift of sodium current reversal potential. Moreover, results of ongoing researches on peripheral myelinogenesis in rats exposed to CO during gestation will be also summarized.

Animals↗

Irreversible impairment of active avoidance behavior in rats prenatally exposed to mild concentrations of carbon monoxide.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) significantly impairs the acquisition of a two-way active avoidance task in 3-month-old male rats as well as the acquisition and reacquisition of this schedule in 18-month-old animals subjected to six daily 20-trial sessions. These deficits do not seem to be attributable to alterations of a non-associative nature, as the intertrial activity and the escape response latencies in CO exposed animals were not significantly affected with respect to controls. These findings, showing that gestational exposure to CO induces in rat offspring permanent learning and memory impairment, confirm that the offspring of smoking mothers may be at considerably greater risk than current epidemiological studies on birthweight and neonatal mortality suggest.

Animals↗

Lectin binding pattern of Schwann cells and macrophages in 2,5-hexanedione-induced axonal degeneration in rats.

The lectin binding pattern of both Schwann cells and macrophages has been studied during axonal degeneration induced in the rat sciatic nerve by chronic administration of 2,5-hexanedione (0.8 ml/kg per day i.p. for 20 days). In particular, the present study aimed to establish a possible relationship between macrophage activation and expression of lectin binding sites. To identify and distinguish between Schwann cells and macrophages, electron microscopy was combined with the lectin staining method. On 2,5-hexanedione injury, a drastic disorganization of both axon and myelin sheath occurred and nerve fibers were replaced by a chain of ovoids. Besides the well-established concept that Schwann cells and macrophages cooperate in the removal of the myelin debris during axonal degeneration, evidence is presented that expression of binding sites to lectins is closely related to macrophage activation. Monocytes occasionally present in control nerves were labelled only by Con A and sialidase-peanut sequence; in 2,5-hexanedione degeneration monocytes, prephagocytes (macrophages with minute bubbles) and phagocytes (macrophages with large bubbles) were labelled also by peanut, wheat germ and BSA I-B4; moreover, phagocytes were labelled by soybean as well, thus showing a clearly differentiation-dependent binding pattern. Since changes in lectin binding pattern may reflect changes in complex carbohydrate structures, the results show that the expression of certain glycoproteins may be closely related to activation of macrophages in response to toxic injuries.

Animals↗

(+)-N-allylnormetazocine enhances N-acetyltransferase activity and melatonin synthesis: preliminary evidence for a functional role of sigma receptors in the rat pineal gland.

In the present study, to evaluate the role that sigma receptors play in the physiology of the pineal gland, we assessed the effects of the sigma receptor ligand (+)-N-allylnormetazocine on the gland activity during either the day or the night. As compared to saline, (+)-N-allylnormetazocine enhanced the physiological increases in both pineal N-acetyltransferase (NAT) activity and melatonin content at night, but it did not affect the biosynthetic activity of the gland during the day. Moreover, (+)-N-allylnormetazocine potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during the day. The nocturnal stimulation of pineal NAT activity and melatonin levels by (+)-N-allylnormetazocine was prevented by pretreatment with rimcazole, a specific sigma receptor antagonist. These results demonstrate that sigma receptor activation by (+)-N-allylnormetazocine is not able, by itself, to stimulate pineal melatonin production, whereas it potentiates the biosynthetic activity of the pineal gland when this is stimulated noradrenergically.

Animals↗

Alterations in the ontogeny of rat pup ultrasonic vocalization produced by prenatal exposure to nitrogen dioxide.

Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.

Aging↗

In vivo fluorescence and photodynamic activity of zinc phthalocyanine administered in liposomes.

Zinc(II) phthalocyanine, a hydrophobic photosensitiser, was incorporated in unilamellar liposomes and studied in vivo for fluorescence kinetics and photodynamic activity. An observation chamber mounted in a dorsal skinfold of female WAG/Rij rats was used as a model system. In the chamber, an isogeneic mammary carcinoma was transplanted in the subcutaneous tissue. Phthalocyanine fluorescence was excited at 610 nm with a power density of 0.25 mW cm-2 and was detected above 665 nm through a high-pass filter using a two-stage image intensifier coupled to a charge-coupled device (CCD) camera. Following i.v. administration of 0.14 mg kg-1 of the drug, the fluorescence pharmacokinetics of the dye in vasculature, normal tissue and tumour tissue was determined as a function of time. Tumour fluorescence increased slowly to a maximum about 3 h post injection (p.i.), and remained well above the normal tissue fluorescence till 24 h p.i. Fluorescence in the circulation was always stronger than in the tissues. A treatment light dose at a wavelength of 675 nm was delivered 24 h p.i. One group of six animals received a total light dose of 150 J cm-2 (100 mW cm-2). A second group of six animals received a total light dose of 450 J cm-2 at the same dose rate. Vascular damage resulting from treatment was observed only at the final stages of the irradiation, despite the relatively high levels of fluorescence in the circulation. Immediate post-treatment (re)transplantation of the content of the chamber into the flank always resulted in tumour regrowth, confirming the presence of viable tumour cells following photodynamic therapy (PDT). When the chamber was left intact, the light dose of 450 J cm-2 yielded complete tissue necrosis. The role of the dye-carrier complex in shielding the vascular surrounding from photoproducts was studied in a third group of animals. The presence of peroxides was demonstrated in the serum of these animals after PDT with zinc phthalocyanine in liposomes (ZnPc-lip) using a total light dose of 450 J cm-2. This ex vivo observation supports the previously reported observations in vitro that the carrier complex is able to quench the photoproducts resulting from photoactivation of the photosensitiser which is present in the circulation.

Animals↗

Changes in the frequency of splenic immunocompetent cells in rats exposed to carbon monoxide during gestation.

The aim of the present study was to evaluate whether prenatal exposure to relatively low concentrations of carbon monoxide (CO) may alter the frequency of splenic cells either in young (15-21 days) or in aged rats (18 months). Wistar female rats were exposed to 75 and 150 ppm of CO from day 0 to day 20 of pregnancy, respectively. The results show that prenatal exposure to 150 ppm of CO significantly decreases the number of leucocyte common antigen (LCA+) cells in 21 day old male rats, whereas other cellular populations, such as macrophages, Major Histocompatibility (MHC) II cells, T and B lymphocytes display only a trend towards a reduction without achieving statistical significance. The alterations in LCA+ cell frequency produced by gestational exposure to CO were reversible. These data further extend previous findings showing that rats prenatally exposed to moderate concentrations of CO exhibit subtle immunological changes in the absence of overt signs of toxicity.

Aging↗

Atrial natriuretic factor antagonises angiotensin II--induced vasopressin release in rat subfornical organ.

The coexistence of Atrial Natriuretic Factor (ANF) and Angiotensin II (Ang II) receptors in the subfornical organ suggested that ANF may influence the action of Ang II at this level. To test this hypothesis the effect of ANF pre injected into subfornical organ (SFO) on Ang II-induced vasopressin release was investigated in rats. ANF blunted vasopressin release elicited by circulating Ang II. This study indicates SFO as one of the main sites at which ANF-Ang II interactions occur.

Angiotensin II↗

Selective activation of glutamate receptor NMDA subtype induces plasma vasopressin increase in rats.

Studies were carried out in the rat to investigate whether glutamic acid is involved in the regulation of vasopressin (VP) release. For this purpose plasma VP levels were measured in rats treated with the glutamate agonist N-methyl-D-aspartate (NMDA). In our experimental conditions NMDA induced dose-related increases in plasma VP levels in normohydrated rats. The effect of NMDA were prevented by 3[(+)-2 carboxy-piperazine-4-yl]propyl-1-phosphonic acid (CPP), a selective and competitive antagonist of NMDA receptors. These data show that glutamate may contribute to the physiological release of VP from the neurohypophysis.

Animals↗

Neurobehavioral changes produced in rats by prenatal exposure to carbon monoxide.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (75 and 150 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to CO (150 ppm) produced a significant reduction in the minimum frequency of ultrasonic calls emitted by rat pups removed from their nest. Moreover, a significant decrease in the responsiveness (rate of calling) to a challenge dose of diazepam (0.25 mg/kg) was found in male pups exposed to CO (150 ppm) during gestation. Prenatal CO (75 and 150 ppm) did not significantly affect locomotor activity or D-amphetamine-induced hyperactivity in both 14- and 21-day-old animals. Furthermore, adult male rats exposed to this chemical (150 ppm) during gestation exhibited significant alterations in the acquisition of an active avoidance task. CO-induced learning disruption does not seem to be linked to changes in the emotionality of animals. These findings suggest that gestational exposure to CO induces in rat offspring both short- and long-term behavioral changes characterized by altered ontogeny of emotional responsiveness to environmental challenges and by learning impairment.

Analysis of Variance↗

Changes in peripheral nervous system activity produced in rats by prenatal exposure to carbon monoxide.

The present experiments were designed to investigate whether alterations of peripheral nervous system activity may be produced in male Wistar rats by prenatal exposure (from day 0 to day 20 of pregnancy) to relatively low levels of CO (75 and 150 ppm). The voltage clamp analysis of ionic currents recorded from sciatic nerve fibres showed that prenatal exposure to CO produced modifications of sodium current properties. In particular, in 40-day-old rats exposed to CO (75 and 150 ppm) during gestation, the inactivation kinetics of transient sodium current were significantly slowed. Analysis of the potential dependence of steady-state Na inactivation, h infinity (V), showed that the percentage of the maximum number of activable Na channels at the normal resting potential (-80 mV) was increased to approximately 85% in CO-exposed rats. Moreover, the voltage-current relationship showed a negative shift of sodium equilibrium potential in CO treated animals. In 270-day-old CO-exposed rats, parameters of sodium inactivation were not significantly modified; the reversal potential was still lower with respect to controls. The results indicate that prenatal exposure to mild CO concentrations produces reversible changes in sodium inactivation kinetics and on irreversible change in sodium equilibrium potential. These alterations could reflect CO influence on the rate of ion channel development.

Animals↗

Behavioral changes produced in rats by developmental exposure to flumazenil, a benzodiazepine receptor antagonist.

1. Prolonged administration of a benzodiazepine receptor antagonist, such as flumazenil (given to the mother at a dose of 3 mg/kg s.c. from day 14 to day 20 of gestation), produced subtle behavioral changes in rat pups. 2. Flumazenil treatment decreased the rate of ultrasonic vocalization in 15-day old male pups removed from their nest. 3. No significant changes in the locomotor activity of the flumazenil-treated group with respect to controls was found at the end of the second and fourth postnatal week. 4. These results suggest that late prenatal exposure to flumazenil induces in rat offspring behavioral changes characterized by decreased emotional responsiveness to environmental challenges.

Analysis of Variance↗

Immunological changes produced in rats by prenatal exposure to carbon monoxide.

Wistar female rats were exposed to relatively mild concentrations of carbon monoxide (CO) (75 and 150 p.p.m.) from day 0 to day 20 of pregnancy. The results show that splenic macrophage phagocytosis of Candida albicans was significantly decreased in 15 and 21 day old male rats exposed to CO (150 p.p.m.) during pregnancy. Moreover, splenic macrophage killing was significantly reduced in 15 day old male pups prenatally exposed to 75 and 150 ppm of CO. Prenatal CO (150 p.p.m.) significantly decreased splenic macrophage O2- release in both 15 and 21 day old pups. CO-induced alterations in the immune system were not observed in 60 day old rats. These findings indicate that gestational exposure to relatively mild concentrations of CO induces in rat offspring reversible immunological changes characterized by an altered splenic macrophage function.

Animals↗