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Biomedical subjects

A Loizzo

Publications and source records attributed to A Loizzo.

At least 37 records · Page 2Linked to original sources

Dexamethasone modifies the behavioral effects induced by clonidine in mice.

The present study examines the influence of dexamethasone on behavioral effects induced by clonidine in mice. 2. The behavior elements considered were locomoter activity, rota rod, catalepsy and stereotyped behavior (rearing, grooming, social response test, crossing, smelling, washing face, scratching and bar holding). 3. Clonidine (0.1-0.5-1.0 mg/kg, IP) induced a significant reduction of all behavioral elements studied when compared to the saline treated group: the behavioral reduction was significant 10 min after administration and lasted for the entire recording period (120 min). 4. Dexamethasone (0.1-0.5-1.0 mg/kg, IP) per se did not induce significant changes in the behavior elements recorded. 5. Dexamethasone (0.1-0.5 mg/kg, IP) dod not affect behavioral effects induced by the 3 doses of clonidine, whereas the high dose (1 mg/kg) of the steroid significantly reduced its behavioral inhibition. 6. The results of the present study suggest that dexamethasone induces significant effects on clonidine-induced behavioral effects and that this may be related to an interference with the monoaminergic system.

Animals↗

Effects of low doses of physostigmine on avoidance learning and EEG in two strains of mice.

The effects of the cholinomimetic drug, physostigmine (0, 0.01, 0.025, 0.05 and 0.1 mg/kg, i.p.), on shuttle-box avoidance learning and electroencephalographic (EEG) activity were investigated, in two separate studies, in mice belonging to the inbred C57BL/6 (C57) and DBA/2 (DBA) strains. The results of the behavioral investigation showed a consistent, significant enhancement of avoidance performance, on the whole of 5 daily training sessions, in C57 mice treated with the lowest dose (0.01 mg/kg) and in DBA mice treated with the highest doses (0.05 and 0.1 mg/kg) of the drug. Doses higher than 0.01 mg/kg, in C57 mice, and lower than 0.05 mg/kg, in DBA mice, had no significant effect. The avoidance improvements induced by physostigmine cannot be ascribed to general behavioral activation, since the doses that increased avoidance responses did not affect or even depressed spontaneous locomotor activity. The same doses of treatment which increased avoidance responding, also induced, in the same strains, consistent enhancement of 4-7 Hz (theta) EEG band power and decrease of 7-12 Hz (alpha) band power. Results suggest that the effects induced by physostigmine on the EEG and on the shuttle-box performance of mice are related to the same neurochemical systems, and are dependent upon the interaction of the dose with specific strain sensitivity.

Animals↗

Prescriptions for mesalazine and sulphasalazine: a prevalence estimate of patients treated for inflammatory bowel disease in Rome.

BACKGROUND: Sulphasalazine and 5-amino salicyclic acid drugs are specifically indicated for the treatment of inflammatory bowel disease. AIM: To use drug consumption by a given population as a marker to estimate the number of patients with inflammatory bowel disease. METHODS: Prescriptions for sulphasalazine and mesalazine were identified for the 133000 inhabitants of a local health unit in Rome. Other prescriptions received by the patients, who were users of sulphasalazine or mesalazine, were also studied. RESULTS: 99465 patients received at least one prescription for any drug in 1991. Three hundred and seventy-six patients were prescribed sulphasalazine and/or mesalazine, an average of 3.8 prescriptions per patient. These patients were exposed more frequently than the general population to other drugs often used in inflammatory bowel disease treatment, for example, corticosteroids, anti-diarrhoeal drugs and intestinal anti-infectives. We identified that 258 of 100000 inhabitants were prescribed either sulphasalazine or mesalazine; 127 of 100000 inhabitants received full-dose treatment for at least 30 days, and 42.8 of 100000 inhabitants received prescriptions of either drug, also associated with systemic corticosteroids. CONCLUSION: The consumption of drugs used specifically for inflammatory bowel disease may act as a marker for the prevalence of the condition in a community.

Aminosalicylic Acids↗

Dexamethasone reduced clonidine-induced hypoactivity in mice.

Reduced clonidine anti-nociception in mice given low doses of dexamethasone has encouraged us to investigate the effects of dexamethasone pretreatment on locomotor hypoactivity, another example of clonidine-induced behaviour in mice. Dexamethasone administered intraperitoneally (0.1, 1.0, 10 mg kg-1) 30 min before clonidine reduced clonidine-induced locomotor hypoactivity in the activity cage to an extent which was dose-dependent. Dexamethasone administered centrally (10 ng/mouse) 30 min before clonidine was also able to reduce clonidine-induced locomotor hypoactivity. Cycloheximide administered at a dose of 10 mg kg-1 2 h before clonidine did not change the effects of clonidine but was able to prevent the effects of dexamethasone on clonidine-induced hypoactivity. The glucocorticoid receptor antagonist RU38486 administered centrally at the dose of 1 ng/mouse did not change the effects of clonidine, whereas it was able to block the effects of dexamethasone on clonidine-induced locomotor hypoactivity. These results suggest that the effects of dexamethasone on clonidine-induced locomotor hypoactivity depend on the stimulating effects that dexamethasone exerts on the protein synthesis via the glucocorticoid receptor in the brain.

Adrenergic alpha-Agonists↗

Dexamethasone selective inhibition of acute opioid physical dependence in isolated tissues.

The effect of dexamethasone on acute opiate withdrawal induced by mu, kappa and delta receptor agonists was investigated in vitro. After a 4-min in vitro exposure to morphine (less selective mu agonist), D-Ala2-N-methyl-Phe4-Gly5-ol)-enkephalin (DAGO; highly selective mu agonist) and trans(+/-)-3,4-dichloro-N-methyl-N-[2(1-pyrrolidynyl)cyclohexyl]- benzeneacetamide (U50-488H; highly selective kappa agonist) a strong contracture of guinea pig isolated ileum was observed after the addition of naloxone. This effect was also observed when rabbit isolated jejunum was pretreated with deltorphin (highly selective delta agonist). Dexamethasone treatment before or after the opioid agonists tested was capable of both preventing and reverting the naloxone-induced contracture after exposure to mu opiate agonists morphine and DAGO in a concentration- and time-dependent fashion. Also, the steroid reduced naloxone-induced contracture after the exposure to U50-488H only when injected before the kappa opiate agonist. Finally, it did not affect the naloxone contracture after exposure to deltorphin. Pretreatment with RU-38486, a glucocorticoid receptor antagonist, inhibited dexamethasone antagonism on responses to both mu and kappa agonists, whereas pretreatment with cycloheximide, a protein synthesis inhibitor, blocked only the antagonistic effects of dexamethasone on responses to the mu opioid agonists. Overall, these data indicate that dexamethasone induces significant effects on mu-mediated opiate with-drawal in vitro, which suggest an important functional interaction between corticosteroids and the opioid system primarily at the mu receptor level. The ability of RU-38486 and cycloheximide to block dexamethasone effects indicates that the steroid interference on mu-mediated withdrawal involves a protein synthesis-dependent mechanism via glucocorticoid receptor.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Trihalomethanes in drinking water and cancer: risk assessment and integrated evaluation of available data, in animals and humans.

In our study, we attempted to jointly consider THM concentration data collected from drinking waters and carcinogenic risk assessment derived from mathematical models commonly used in this field (multi-stage models for laboratory animal experimentation data, and 'unit risk' derived from the relative risk in the case of epidemiological data). In order to estimate the risks related to joint exposure to different THMs, in this study the risk additivity hypothesis is taken into account. Based on animal data for the various tumors, carcinogenic risk estimates for different THM combinations vary from 2.7 x 10(-7) to 4.6 x 10(-6) per micrograms/l in relation to different carcinogenic substances published in the literature or specifically calculated in this study. The carcinogenic risk parameters derived from experimental studies and from epidemiological data were substantially consistent. Our study uses also as an example some data on concentration levels of THMs for drinking water supplies in Sardinia. The area mean THM concentration values for each supply varied, for ground waters, from 8.1 to 13.6 micrograms/l and, for surface waters, from 52.8 to 168 micrograms/l. For the 1976-1989 period, bladder cancer standardized mortality rates in the water distribution system areas where the THMs were measured indicate values similar, but generally lower, than the national ones, except in the province of Cagliari where the values were not significantly different. The risk estimates derived from animal studies are of the same order of magnitude as the epidemiological data in literature.

Animals↗

Reduced hippocampal CA1 Ca(2+)-induced long-term potentiation is associated with age-dependent impairment of spatial learning.

Expression of Ca(2+)-induced CA1 long-term potentiation (LTP) was analysed in hippocampal slices obtained from (1) 3-month-old and (2) 18-20-month-old Sprague-Dawley rats selected for their performances in the Morris water maze task. In all slices, a transient (10 min) increase of extracellular Ca2+ concentration (4 mM) caused a long-lasting enhancement of potentials evoked by electrical stimulation of radiatum fibers. However, a significant difference was found in the degree of potentiation among groups. In particular, increases of the CA1 response amplitudes were significantly lower in old rats impaired in spatial learning than in young at 30 (P < 0.05), 60, 90 and 120 min (P < 0.01) after restoring the normal Ca2+ concentration. On the contrary, no differences were observed between young animals and the old ones with good performances in spatial learning. The data suggest that amplitude of CA1 Ca(2+)-induced LTP in old rats is related to spatial learning abilities.

Aging↗

Time-related antiepileptic effects of the synthetic glucocorticoid dexamethasone in rat hippocampal slices.

The in vitro antiepileptic activity of the synthetic glucocorticoid dexamethasone (DEX) was tested in rat hippocampal slices on the CA1 epileptiform activity induced by sodium penicillin (PEN). Slice perfusion with 1 mM PEN produced within 60 min the development of a CA1 epileptiform bursting made up of an increase of the primary CA1 population spike followed by the appearance of secondary epileptiform population spikes. Slice perfusion with 100 microM DEX together with PEN (1 mM) partially prevented but did not block the expression of the CA1 epileptiform bursting as evidenced by a significant (P < 0.05) reduction of the duration of the bursting due to the epileptogenic agent. Slice perfusion with 50 microM DEX together with PEN (1 mM) failed to prevent or block the expression of the CA1 penicillin-induced epileptiform bursting. A 60 min slice pretreatment with 50-100 microM DEX followed by a slice perfusion with 50-100 microM DEX together with PEN (1 mM) prevented the expression of the CA1 epileptiform bursting. Cycloheximide (1 microM), a protein synthesis inhibitor, perfused together with DEX reverted the inhibitory effects of dexamethasone on the expression of the penicillin-induced CA1 epileptiform bursting. The results indicate that the synthetic glucocorticoid DEX presents concentration- and time-related in vitro antiepileptic effects. In addition, the data suggest that this inhibitory effect occurs via a protein synthesis-dependent mechanism.

Action Potentials↗

Long-term changes induced by neonatal handling in the nociceptive threshold and body weight in mice.

During the first 3 weeks of life, four litters of CD-1 male mice were daily handled (HA group) and four other litters were left undisturbed (UHA group). At 35 days of life, mice underwent the tail flick (TF) and hot plate (HP) tests to measure the baseline reaction to thermal nociceptive stimulation. At the age of 50, 80, and 140 days body weight was measured. At the last time point the epididymal fat pads (EFPs) were also taken and weighed. We found that, 16 days after the suspension of the manipulation. HA mice showed increased latencies to both nociceptive tests and, starting on day 80, they began to develop a significant increment in body weight. An increase was also evident in EFP weight of HA mice.

Animals↗

Ultradian rhythms in the N1-P2 amplitude of the visual evoked potential in two inbred strains of mice: DBA/2J and C57BL/6.

Ultradian rhythmicity has been showed in many behavioural parameters in animals as well as in humans. We investigated the existence of a Basic Rest-Activity Cycle (BRAC) rhythm in amplitude fluctuations of mice's visual evoked potential (VEP) primary component. Two inbred strains of mice, C57BL/6 and DBA/2J, were used to verify the influence of genetics on biological rhythm as well. Results revealed the existence of an evident rhythm in the parameter under study and confirm previous reports of a 20 min. BRAC in avoidance behavior in DBA mice. This rhythm shows similar period within each strain, but significatively different periods between strains. Observed periods are near to species-specific reported BRAC cycle. Genetic hypothesys is suggested to explain differences between strains in expression of ultradian rhythm.

Animals↗

Dexamethasone pretreatment reduces the psychomotor stimulant effects induced by cocaine and amphetamine in mice.

1. The present study examined a comparison of the effect of DEX on psychomotor stimulant effects of cocaine and amphetamine in mice by using the locomotor activity test. 2. Cocaine (10 mg/kg/i.p.) and amphetamine (5 mg/kg/i.p.) increased markedly locomotor activity of mice whereas DEX per se (0.1-1.0-10 mg/kg/i.p.) did not modify the activity of control mice. 3. DEX pretreatment decreased the stimulating effects induced both by cocaine and amphetamine but no consistent dose-related effects were observed. 4. The results suggest that DEX may play an important role on the stimulating effects of cocaine and amphetamine and that it may be of some utility in the clinical management of psychostimulants abuse.

Amphetamine↗

Dexamethasone reduces the behavioural effects induced by baclofen in mice.

The present study examines the influence of dexamethasone on the behavioural effects induced by baclofen in mice. The behaviour elements considered were locomotor activity, motor co-ordination, catalepsy, stereotyped behaviour and antinociception. Baclofen (1.0-4.0-6.0 mg kg-1, i.p.) induced a significant reduction of all behavioural elements studied and an antinociceptive effect was recorded. Dexamethasone alone (0.1-0.5-1.0 mg kg-1, i.p.) did not induce significant changes in the behaviour elements considered. On the other hand, when the steroid was injected immediately before baclofen a significant reduction of baclofen's behavioural effects was found. Our results suggest a possible link between glucocorticoid and the GABA-ergic system.

Animals↗

Clinical pharmacokinetics of cumulative very high dose of cisplatin in chemotherapy resistant solid tumors.

Cisplatin was administered to seven patients with advanced cancer in divided doses of 40 mg/m2 body surface daily for 5 consecutive days. The pharmacokinetics of total Pt was studied on the days 1, 3 and 5 of infusion. The renal function was assessed through the parameters usually applied in the clinical practice (serum creatinine level, creatinine clearance, urinary volume). Pt pharmacokinetics and the renal function did not show modifications outside the normal range. However, on day 5 of treatment patients showed increased alpha-half life and AUC of plasma Pt, as well as decreased Pt total body clearance and Pt renal clearance, associated to a significant (although still within normal range) increase in serum creatinine and a decrease in urinary volume. Moreover, a correlation between Pt pharmacokinetics and renal parameters (measured as the difference between the values of days 1 and 5 of treatment) was also found: the increase in creatinine was directly related to a decrease in Pt renal clearance and inversely related to Pt peak level in urine, while the latter was inversely related to a reduction of Pt renal clearance. It was concluded that very high doses of cisplatin are well tolerated in patients, although some parameters might suggest early impairment of the renal function.

Aged↗

Effect of des-tyrosine-gamma-endorphin on neocortical spike-and-wave spindling in DBA/2J mice.

The effect of a beta-endorphin cleavage product devoid of opioid effects, des-tyrosine-gamma-endorphin (DT gamma E) on the neocortical spike-and-wave spindling episodes in the electrocorticogram (ECoG) of DBA/2J mice was studied. DT gamma E (0.01-1.0 mg/kg, i.p.) dose dependently reduced the spike-and-wave bursts duration. However, the low dose did not induce consistent modifications of the spike-and-wave bursts number while the dose of 0.1 and 1.0 mg/kg induced a progressive diminution. Furthermore, at all doses DT gamma E did not induce any alterations of the spike-and-wave bursts amplitude, frequency, and desynchronized activity when compared to the pre-drug period. These results indicate that this beta-endorphin fragment may affect brain excitability.

Animals↗

Age and strain differences in rat place learning and hippocampal dentate gyrus frequency-potentiation.

Induction of post-tetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from (i) young (6 months old) rats of different strains (Sprague-Dawley, SD; spontaneously hypertensive rats, SHR; and Wistar-Kyoto, WKY), and (ii) from aged (20-24 months old) SD and Fischer 344 (F 344) rats, each group showing a different performance in the Morris maze test. After the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum moleculare, a significant difference was found in the percent of induction of the dentate PTP in hippocampal slices obtained from rats of different strains and ages. In particular, the induction of the dentate PTP was significantly (P < 0.01) higher in slices obtained from young SD or spontaneously SHR rats, having the better performance in the Morris maze than in slices obtained from old SD or F 344 rats or young WKY rats which had poorer performances in the Morris maze. On the contrary, no significant differences were found in the percent of induction of the LTP in the dentate area of hippocampal slices obtained from rats of different strains and ages. Moreover, after the application of an electrical tetanus (1 s, 100 Hz, 50 microA) in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Effects induced by cysteamine on chemically-induced nociception in mice.

The effects were investigated of cysteamine--a well known somatostatin depletor--on the pain induced by chemical stimuli in mice. Cysteamine injected intraperitoneally 4 h before the test at doses of 50 and 100 mg/kg reduced the second phase of the licking response which was induced by formalin injected into the hind paw. Furthermore, cysteamine administered at the doses of 10, 50 and 100 mg/kg reduced the writhing induced by acetic acid. Naloxone, yohimbine and CGP 35348 administered in cysteamine-pretreated animals were not able to change the cysteamine antinociceptive effects in the formalin test. Intrathecally injected somatostatin was able to revert the cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test, whereas intracerebroventricularly injected somatostatin reduced the antinociceptive effects induced by cysteamine in the second phase of the formalin test. Intrathecally injected cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl])--a reported somatostatin antagonist--increased cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test. These results suggest that somatostatin is involved in the effects of cysteamine on the nociceptive threshold.

Amino Acid Sequence↗

Phencyclidine reduces inherited neocortical spindling in DBA/2J mice.

The role of phencyclidine (PCP) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. PCP (0.1-0.5-1.0-5.0 mg/kg/i.p.) dose dependently reduced both S&W number and duration of DBA/2J mice. PCP reduction is significant 30-60 min after drug administration and lasts for the whole duration of the recording period (240 min). These results suggest that PCP may play an important regulatory role on brain excitability.

Animals↗

Dexamethasone influence on morphine-induced analgesia in outbred Swiss and inbred DBA/2J and C57BL/6 mice.

1. The influence of dexamethasone on morphine analgesia in three different strains of mice (Swiss, DBA/2J and C57BL/6) was studied by using the tail flick test. 2. I.c.v. as well as i.p. injections of dexamethasone did not modify nociceptive response in all strains. 3. I.c.v. injection of dexamethasone significantly reduced morphine analgesia in Swiss mice whereas no effects were observed in DBA/2J and C57BL/6 mice. 4. In addition, i.p. injection of dexamethasone significantly reduced morphine analgesia in all three strains. 5. These results suggest that the use of different genetic strains may provide an useful approach for studying dexamethasone-morphine analgesia interaction.

Analgesia↗