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V Cuomo

Publications and source records attributed to V Cuomo.

At least 37 records · Page 2Linked to original sources
PubMed2000

Chronic low dose ethanol intake: biochemical characterization of liver mitochondria in rats.

Liver mitochondria were isolated from male rats exposed for 2 months to low doses of ethanol (3% v/v in drinking water), a condition not associated with tolerance or dependence. The results show no significant changes in the content of reduced or oxidized glutathione in the liver mitochondria of ethanol treated rats with respect to controls. However, a slight but significant increase in lipid peroxidation, accompanied by an increased content of oxidized proteins, was found in ethanol exposed animals. Mitochondrial content of cytochrome complexes was not significantly affected by ethanol intake. The specific enzymatic activity of cytochrome oxidase showed, however, a significant decrease in ethanol-treated rats. The slight mitochondrial alterations found in the liver of rats exposed chronically to low doses of ethanol might represent the beginning of a more extensive damage previously observed in rats exposed to high doses of this substance.

Animals↗
PubMed2000

Role of different dialysis membranes in the release of interleukin-6-soluble receptor in uremic patients.

BACKGROUND: Interleukin-6 (IL-6) exerts its actions through a cell-surface receptor system that consists of two transmembrane subunits: the IL-6 binding glycoprotein gp 80 (IL-6R) and the signal-transducing component (gp 130). Soluble forms of the IL-6R (sIL-6R) are generated by shedding of the membrane-associated proteins. The sIL-6R binds the ligand IL-6 with comparable affinity as the membrane-associated IL-6R and enhances the actions of IL-6. METHODS: Our aim was to evaluate the role of both uremia and different dialysis membranes on peripheral blood mononuclear cell (PBMC) release (either in absence or in presence of mitogen stimulation) and plasma levels of sIL-6R. Ten patients chronically dialyzed with cuprophan membranes (CU), eight patients on regular dialysis treatment with polymethylmethacrylate (PMMA) membranes, 11 uremic nondialyzed patients (UR), and 12 healthy subjects (CON) were included in the study. RESULTS: PBMCs harvested from CU spontaneously released significantly (P < 0.01) greater amounts of sIL-6R (881.8 +/- 80.1 pg/mL), as compared with CON (267.5 +/- 26.5 pg/mL), UR (258.4 +/- 38.1 pg/mL), and PMMA (288.4 +/- 24.6 pg/mL). Under mitogenic stimulation, the sIL-6R release was significantly (P < 0.01) increased in all groups. The greater PBMC production of sIL-6R in CU was followed by significantly (P < 0.01) higher levels of circulating soluble receptors (48.7 +/- 2.5 ng/mL, 60%), as compared with CON (30.5 +/- 1.9 ng/mL). UR also showed high circulating levels of sIL-6R (53.3 +/- 5.9 ng/mL), probably secondary to an impaired urinary excretion. Circulating levels of sIL-6R in PMMA were comparable to CON (30.3 +/- 3.3 ng/mL). Either the absence of monocyte activation or the adsorption of sIL-6R on the hydrophobic PMMA surface could explain this finding. CONCLUSIONS: These results suggest an important role for poor dialysis biocompatibility of CU on the release of sIL-6R, which increases sIL-6R plasma levels, thereby enhancing the inflammatory effects of IL-6.

Adult↗
PubMed2000

Biochemical and neurobehavioral profile of CHF2819, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease.

1,2,3,3a,8,8a-Hexahydro-1,3a,8-trimethylpyrrolo¿2,3-bĭndol-5-ol 2-ethylphenylcarbamate N-oxide hydrochloride (3aS-cis) (CHF2819) is a novel acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral administration in rats. In vivo studies show that CHF2819 (0.5, 1.5, and 4.5 mg/kg p.o.) significantly increases acetylcholine levels in young adult rat hippocampus in a dose-dependent manner. Moreover, aged animals, which show a significant decrease in basal acetylcholine levels with respect to young adult rats, also exhibit a marked increase in the hippocampal concentrations of this neurotransmitter after the administration of CHF2819. This compound (1.5 mg/kg p.o.) significantly attenuates scopolamine-induced amnesia in a passive avoidance task. Furthermore, CHF2819 induces a significant decrease in dopamine levels and a significant elevation of extracellular concentrations of 5-hydroxytryptamine, whereas it does not modify norepinephrine and gamma-aminobutyric acid levels in the hippocampus of young adult rats. Functional observational battery screening demonstrates that CHF2819 (1.5 and 4.5 mg/kg p.o.) does not affect activity, excitability, autonomic, neuromuscular, and sensorimotor domains, as well as physiological end points (body weight and temperature). However, this compound induces involuntary motor movements (ranging from mild tremors to myoclonic jerks) in a dose-dependent manner. These findings suggest that the anti-amnestic properties of CHF2819, together with its stimulatory effect on cholinergic and serotonergic functions, might have a therapeutic potential mainly for the symptomatic treatment of Alzheimer's disease patients in which the cognitive impairment is accompanied by a depressive syndrome.

Acetylcholine↗
PubMed2000

Prenatal exposure to a low concentration of carbon monoxide disrupts hippocampal long-term potentiation in rat offspring.

The aim of the present study was to investigate whether functional changes at CA3-CA1 synapses in the hippocampus could underlie learning and memory deficits produced in rat offspring by a prenatal exposure model simulating the carbon monoxide (CO) exposure observed in human cigarette smokers. Electrophysiological endpoints, including long-term potentiation, were examined in 15- to 30-day-old male rats whose mothers were exposed, from day 0 to day 20 of gestation, to 150 ppm of CO resulting in blood levels of carboxyhemoglobin comparable to those found in human cigarette smokers. Evoked field excitatory postsynaptic potentials were measured in the stratum radiatum in hippocampal slices. Results show that before tetanus, input/output functions, presynaptic volley, and paired-pulse facilitation were not affected in CO-exposed offspring, indicating that basal synaptic excitability and terminal Ca(2+) influx were not influenced by prenatal exposure to this gas. Conversely, evoked field excitatory postsynaptic potentials potentiation in response to tetanization was reduced by about 23% and decayed rapidly to baseline values in slices from CO-exposed animals. No changes between and within groups were observed in paired-pulse facilitation after tetanus. The selective impairment of long-term potentiation expression exhibited by CO-exposed rats was paralleled by a significant decrease in heme-oxygenase 2 and neuronal nitric-oxide synthase in the hippocampus. No changes in either enzymatic activity were found in frontal cortex and cerebellum. These electrophysiological and biochemical alterations might account for cognitive deficits previously observed in rats exposed prenatally to CO. Our findings could have clinical implications for the offspring of mothers who smoke during pregnancy.

Animals↗
PubMed2000

Serotonergic modulation of rat pineal gland activity: in vivo evidence for a 5-Hydroxytryptamine(2C) receptor involvement.

There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT(2) receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal basal biosynthetic activity of the gland. At night, m-CPP and 1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantly the physiological increases in both pineal NAT activity and melatonin content. This enhancement was prevented by pretreatment with N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT(2B/C) than for 5-HT(2A) receptor, as well as by pretreatment with 8-[5-(2, 4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-o xopent hyl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT(2C) receptor now available, but not by pretreatment with ketanserin, an antagonist with higher affinity for 5-HT(2A) than for 5-HT(2C) receptor. These results suggest that 5-HT(2C) receptors are likely involved in the mediation of the serotonergic modulation of pineal biosynthetic activity in rats.

Amphetamines↗
PubMed2000

Plasma homocysteine and microvascular complications in type 1 diabetes.

BACKGROUND: Homocysteine is involved in a complex and dynamic system of vascular injury and repair and may thus contribute to the development of diabetic microangiopathy. This still debated issue has important scientific and clinical implications, since hyperhomocysteinemia can be corrected nutritionally. AIMS: 1) To evaluate the association between fasting plasma homocysteine, type 1 diabetes and its microvascular complications; 2) to elucidate the basis of this association by investigating the major determinants of plasma homocysteine in relation to diabetic microangiopathy. METHODS: We studied sixty-six consecutive patients with type 1 diabetes mellitus of > 10 years duration and normal serum creatinine (< 115 mumol/L, 1.3 mg/dL), and free from clinically detectable cardiovascular diseases. Forty-four non-diabetic controls were also studied. Plasma concentrations of homocysteine, folate and vitamin B12 were investigated together with the C677T mutation in the gene coding for methylenetetrahydrofolate reductase (MTHFR), a key enzyme in homocysteine metabolism. Renal and retinal diabetic complications were evaluated as albumin/creatinine ratio on early-morning, urine spot collection and fundus photographs. FINDINGS: Fasting plasma homocysteine levels were very similar in patients and controls. Patients with microalbuminuria or proliferative retinopathy had significantly higher values than those without: 9.4 +/- 3.1 vs 7.4 +/- 2.8 mumol/L, p < 0.02 and 9.5 +/- 2.6 vs 7.3 +/- 3.0 mumol/L, p < 0.05. This difference was not attributable to confounders, such as age, sex and smoking, nor to dissimilar plasma folate and vitamin B12 concentrations. In contrast, homozygosity for the C677T mutation in the MTHFR gene--the commonest genetic defect linked to moderately increased plasma homocysteine--was significantly more frequent in patients with microalbuminuria and/or proliferative retinopathy (50% vs 13%, p < 0.004), odds ratio 6.7 (95% CI 1.7-27.6). CONCLUSIONS: Type 1 diabetes as such is not associated with increased plasma homocysteine levels, though patients with microalbuminuria and/or proliferative retinopathy display significantly higher values than those without. This difference is not attributable to obvious confounders, nor to differences in vitamin status, and may be partly mediated by genetic factors. Plasma homocysteine, together with other diabetes-related noxae, may thus be in a position to contribute to the development of nephropathy and the progression of retinopathy.

Adult↗
PubMed1999

Prenatal exposure to low concentrations of carbon monoxide alters habituation and non-spatial working memory in rat offspring.

Inhalation of low concentrations (75 and 150 ppm) of carbon monoxide (CO) by pregnant rats from days 0 to 20 of gestation leads to alterations in habituation and working memory in young adult male offspring subjected to the novel exploration object test. In particular, lack of habituation upon the second presentation of the objects and failure in the ability to discriminate between the novel and the familiar object were found in CO (75 and 150 ppm)-exposed offspring. These alterations were not accompanied by changes in spontaneous motor activity (open field test). The subtle behavioral deficits observed in the present study have been produced by prenatal exposure to CO levels resulting in maternal blood carboxyhaemoglobin (HbCO) concentrations equivalent to those observed in human cigarette smokers.

Animals↗
PubMed1998

Potassium channel modulation by the pseudopeptide ochratoxin A in rat nerve fibers.

Ochratoxin A (OTA), a naturally occurring mycotoxin produced by Aspergillus and Penicillium genera, blocks anion conductance in Madin-Darby canine kidney (MDCK) cells and reduces the potassium concentration gradient in the same cells. So far, a direct effect of OTA on cation channels has not been reported. Experiments were then designed to explore the OTA action on ion channels of rat nerve fibres. Voltage clamp technique has shown that OTA (0.1-1 microM) does not significantly affect sodium current in the intact myelinated axon. After paranodal demyelination (using 0.2% pronase) large K+ outward and K+ tail currents are elicited upon depolarization and repolarization. OTA application on pronase treated fibres produces the following effects: 1) reduction in the amplitude of the tail current with a negligible effect on the time constant of its fast decaying component (modified by pronase application); 2) reduction in potassium conductance to 30% of the control value (i.e., the value in pronase-treated fibres); and 3) reduction in the leakage conductance. Our findings point at the paranodal region of myelinated nerve fibres as a target for the neurotoxic pseudopeptide OTA found as contaminant in food. The uncleaved OTA is effectively acting since pronase fails to cleave it into phenylalanine and OT alpha.

Animals↗
PubMed1998

Maternal cocaine exposure alters mesolimbic dopaminergic function in rat offspring.

Hooded Lister female rats were treated with either saline or cocaine (20 mg/kg s.c.) from gestational day 10 every other day until weaning (postnatal day 25). In vivo microdialysis has shown that maternal cocaine exposure significantly decreases basal extracellular concentrations of dopamine in the nucleus accumbens of young-adult offspring (4 weeks after cessation of cocaine treatment). Moreover, the increase in extracellular dopamine levels induced by a challenge dose of K+ (intracerebral 60 mM K+ artificial cerebrospinal fluid (aCSF) infusion) or cocaine (15 mg/kg i.p.) was significantly attenuated in rats exposed to cocaine during perinatal life with respect to controls. The alterations in mesolimbic dopamine transmission observed in these experiments might underlie behavioral abnormalities induced in rat offspring by maternal exposure to cocaine at dose levels which do not produce gross malformations and/or overt neurotoxic effects.

Animals↗
PubMed1998

Effects of chronic low-dose ethanol intake on sexual behavior in rats.

The effects of 8-week ethanol intake (3% v/v in drinking water) on the sexual activity of male rats were investigated during three experimental sessions with 15-day intersession intervals. Chronic ethanol consumption did not significantly influence any copulatory parameter during the three experimental sessions. The evaluation of ultrasonic emission during sexual behavior showed that rats treated with ethanol exhibited a significant increase of the postejaculatory vocalization length during the third test session. These results indicate that the chronic intake of low doses of ethanol, which does not induce either tolerance or dependence, only slightly affects the motivational state of male rats during sexual activity.

Animals↗
PubMed1998

Effects of prenatal exposure to low concentrations of carbon monoxide on sexual behaviour and mesolimbic dopaminergic function in rat offspring.

1. Inhalation of low concentrations of carbon monoxide (CO) by pregnant rats (75 and 150 p.p.m. from day 0 to day 20 of gestation) leads to changes in mesolimbic dopaminergic transmission associated with an impairment of sexual behaviour in male offspring. 2. Eighty day old males exposed in utero to CO (150 p.p.m.) exhibited a significant increase in mount/ intromission latency as well as a significant decrease in mount/intromission frequency. A significant decrease in ejaculation frequency was also found in CO (150 p.p.m.)-exposed animals. 3. The acute administration of amphetamine, at a dose (0.5 mg kg(-1) s.c.) stimulating copulatory activity in control rats, failed to reduce mount/intromission latency and did not increase mount frequency in 80-day offspring exposed to CO (150 p.p.m.) during gestation. 4. These behavioural alterations were paralleled by neurochemical changes (in vivo microdialysis) showing that prenatal CO exposure, at concentrations (150 p.p.m.) that did not affect basal extracellular levels of dopamine in the nucleus accumbens, blunted the amphetamine (0.5 mg kg(-1) s.c.)-induced increase in dopamine release in 80-day old male rats. 5. No significant changes in either behavioural or neurochemical parameters were observed in 10-month old rats exposed prenatally to CO. 6. Since the alterations in sexual behaviour and dopaminergic transmission have been produced by prenatal exposure to CO levels resulting in maternal blood carboxyhaemoglobin concentrations equivalent to those maintained by human cigarette smokers, the present data further point out the large risk that the smoking mother poses for her offspring.

Amphetamine↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening. I. Background and genesis.

Numerous events over several years culminated in recognition of the need to explicitly evaluate the nervous system as a potential target for environmental chemicals. Based on recommendations from several international expert panels, the International Programme on Chemical Safety (IPCS) sponsored the Collaborative Study on Neurobehavioral Screening Methods. A Steering Committee was created to oversee the project, develop the testing protocol, recruit participating laboratories and review and analyze the data. The protocol specified the tests, the chemicals (supplied from a common source) and the exposure conditions (acute and repeated dosing). Test methods were based upon existing practices in toxicological screening as well as recent advances in neurotoxicity screening. Chemicals were selected to produce different profiles of neurobehavioral effects. Considerable latitude was afforded the participating laboratories in the choice of several key variables (e.g., strain of rat, testing device for motor activity assessment) that could potentially affect the results of the experiments. The approach therefore provided a standardized yet flexible protocol for evaluating the reproducibility of neurobehavioral screening data in diverse laboratory settings.

Animals↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: II. Protocol design and testing procedures.

This paper describes the development of the protocol for the International Programme on Chemical Safety (IPCS)-sponsored Collaborative Study on Neurobehavioral Screening Methods, including background on the methods and chemicals selected, as well as details concerning the conduct of the collaborative study, including proficiency testing, range-finding and main study. Participating laboratories in the collaborative study received training in the conduct and scoring of the behavioral tests and each laboratory received a video training film to train additional personnel as needed. Each of the eight laboratories that chose to participate in the study completed proficiency testing and assessed seven representative chemicals using a functional observational battery and automated motor activity assessment. The seven chemicals studied were acrylamide, bis-acrylamide, p,p'-DDT, lead acetate, parathion, toluene, and triethyl tin. Participants received coded samples of the chemicals from a common source. Each laboratory derived doses for single and repeated administration based on the determination of a within-laboratory acute "top dose." Animal strains were not standardized and laboratory conditions were standardized to a limited degree in order to judge the general utility and robustness of these procedures in a diversity of testing situations.

Animals↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: III. Results of proficiency studies. Steering Group.

The goal of the IPCS Collaborative Study on Neurobehavioral Screening Methods was to determine the intra- and inter-laboratory reliability of a functional observational battery (FOB) and an automated assessment of motor activity in eight laboratories world-wide. The first phase of the Collaborative Study involved training the participants: evidence of training was then evaluated using positive-control compounds. The positive-control studies required the laboratories to identify, using the FOB, specific neurotoxic syndromes produced by acute exposure to p,p'-DDT, parathion, and by short-term repeated dosing with acrylamide. For the sake of expediency, only one dose of each chemical was used instead of collecting dose-response data. Motor activity test chambers were not of uniform design. The laboratories were therefore required to demonstrate adequate sensitivity by the ability to detect statistically-significant activity increases and decreases produced by triadimefon and chlorpromazine, respectively, following acute administration of a range of doses. The resulting FOB and motor activity data showed variability in the magnitude of effects obtained: some of these differences were attributed to miscommunications, difficulties with the techniques or protocol, or the limitations of having only one dose. All laboratories, however, successfully met the criteria set forth by the Study Steering Committee.

Animals↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: IV. Control data. Steering Group.

The goal of the International Programme on Chemical Safety (IPCS) Collaborative Study on Neurobehavioral Screening Methods was to determine the intra- and inter-laboratory reliability of a functional observational battery (FOB) and an automated assessment of motor activity in eight laboratories worldwide. The control data were crucial to the outcome of the studies in terms of sensitivity and reliability of the test measures, which in turn impact on the between-laboratory comparisons of chemical effects. In addition, analyses of control data can aid in determining endpoints that may require modification to improve their sensitivity and reliability. The control data from the eight laboratories were examined in terms of the following parameters: 1) control variability within studies for each laboratory; 2) within-laboratory replicability of control values across studies; 3) within-laboratory stability of control values over the course of testing for a given study; and 4) between-laboratory comparisons of parameters (1), (2), and (3). The analyses indicated considerable differences across endpoints, wherein some measures showed high variability and little replicability, while others were extremely reproducible. Generally, there were similar ranges of variability and replicability of control data across laboratories, although in some cases one or two laboratories were markedly different from the others. The physiological (weight, body temperature) and neuromuscular (grip strength, landing foot splay) endpoints exhibited the least variability, whereas the subjective assessments of reactivity varied the most. These data indicate a reasonable degree of comparability in the data generated in the participating laboratories.

Animals↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: V. Results of chemical testing. Steering Group.

The IPCS Collaborative Study on Neurobehavioral Screening Methods was undertaken to determine the intra- and inter-laboratory reliability of a functional observational battery (FOB) and an automated assessment of motor activity in eight laboratories world-wide. Following the training phase and the conduct of proficiency studies in all laboratories, participants proceeded to test the effects of seven chemicals in both single dose and four-week repeated dosing scenarios. The chemicals studied were acrylamide, bisacrylamide, p,p'-DDT, lead acetate, parathion, toluene, and triethyl tin. Participants received coded samples from a common source. In order to judge the general utility of these procedures in a diversity of testing situations, laboratories conducted the studies under their standard conditions, using their choice of rat strain and test equipment. Chemical does and time of peak effect for acute testing were determined by each laboratory: these parameters were quite similar for some chemicals, but varied greatly for others. The results of the chemical tests indicated that while there was some variability in the data on specific endpoints, all laboratories detected and characterized the effects of all but one of the known neurotoxicants. The one exception (toluene) was probably due to other factors (e.g., dose level, route of administration) rather than lack of sensitivity of the test methods. This study provides extensive data regarding the use of neurobehavioral screening methods over a range of laboratory conditions as well as the reliability, sensitivity, and robustness of the tests to detect neurotoxic potential of chemicals.

Animals↗
PubMed1997

The IPCS Collaborative Study on Neurobehavioral Screening Methods: VII. Summary and conclusions.

In the International Programme on Chemical Safety (IPCS) Collaborative Study on Neurobehavioral Screening Methods, eight participating laboratories used a standard battery of behavioral tests to determine, in rats, the effects of seven representative chemicals following acute and repeated dosing. The results of the collaborative study indicate good agreement across laboratories with regard to the data collected in vehicle controls. It was clear, however, that some behavioral measures had significantly more variability than other tests. The laboratories also demonstrated the ability to detect known neurotoxic chemicals and identify profiles of effects that differed from non-neurotoxic agents. The results of the study suggest that appropriate training of personnel is crucial to ensure the reliability of the test battery. The results also underscore the importance of dose selection in behavioral screening studies, since it is sometimes difficult to determine the specificity of behavioral changes in animals receiving high doses of some chemicals. The collaborative study also emphasizes the need to utilize a battery of tests in screening a wide range of potential neurotoxic agents. Analysis of data from such studies poses unique challenges due to the large number of tests and test times, and the consequent possibility of false positives. Some statistical concerns may be alleviated by grouping the results from tests that measure similar functions into neurobiological domains. Although this approach improves confidence in the biological relevance of chemical-induced changes in behavior, it may also lead to false negatives. The exploration of other statistical approaches to analyze data from experiments using a test battery is encouraged. Nevertheless, results of the collaborative study strongly support the use of behavioral tests in hazard identification.

Animals↗