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Biomedical subjects

F Chiarotti

Publications and source records attributed to F Chiarotti.

69 records · Page 4Linked to original sources

Morphine effects on mouse locomotor/exploratory activity: test dependency, test reliability, uni- and multi-variate analyses.

Drug and toxicant effects on locomotor/exploratory activity can be quite variable depending on the test and the schedule of exposure. In neurobehavioral toxicology and teratology, these interactions can affect the inferences based on the use of selected drugs as probes to assess which regulatory mechanisms are affected by one or the other treatment. The present experiments were aimed at comparing morphine effects in CD-1 mice under three conditions, namely, Varimex apparatus (VAR), toggle floor box (TOGGLE), videotape recording (VIDEO) in a home cage environment. Morphine HCI (0, 10, 33, or 100 mg/kg) was given IP 20 min before the start of a 30-min test session. The same procedure was repeated 24 h later. Results of VAR and TOGGLE tests were: dose 10 was largely ineffective; dose 33 induced depression in VAR and hyperactivity in TOGGLE; dose 100 enhanced activity in TOGGLE. There were no differences between session 1 and 2. VIDEO: Univariate analysis results showed that morphine produced a dose-dependent depression of Rearing and Grooming, and an enhancement of Crossing, again without changes due to repeated exposure. Results of Principal Component Analysis supported a response competition model of the changes observed in the mouse behavioral profile. The videorecording (VIDEO) procedure is the one providing the most accurate picture of changes in locomotor/exploratory activity and drug effects thereon, also allowing a more comprehensive statistical analysis of the relationships between various types of response changes.

Animals↗

Ventricular conduction defects and atrial fibrillation after coronary artery bypass grafting. Multivariate analysis of preoperative, intraoperative and postoperative variables.

Preoperative, intraoperative and postoperative variables, which might play a role in the development of ventricular conduction defects (VCD) and atrial fibrillation (AF) following coronary artery bypass grafting (CABG), were evaluated in 236 consecutive patients. VCD and AF developed postoperatively in 15.5% of patients: 4.5% had VCD (subgroup A), 11.0% had AF (subgroup B). In 84.5% of patients VCD and AF did not occur (subgroup C). Univariate analysis showed statistically significant differences between subgroups A and C with respect to: left main significant stenoses and number of diseased vessels. Bypass pump time and aortic cross-clamp time were significantly longer in subgroup B. Multivariate analysis showed a significantly greater incidence of left main disease and of right coronary artery occlusion associated with significant stenosis of the proximal left anterior descending artery in subgroup A. In subgroup B, the duration of aortic cross-clamp time was significantly higher. Ischaemic injury, with increasing duration of cardioplegic arrest, seems to play a key role in the development of AF. Nonhomogeneous cardioplegic delivery to critical areas of myocardium, and particularly to the specialized conducting system, may cause VCD after CABG.

Adult↗

Progression to AIDS among Italian HIV-seropositive haemophiliacs. Italian Group.

To investigate the interval between HIV-1 infection and the development of clinical AIDS among Italian patients with congenital coagulation disorders, a national cohort study was undertaken in 1988. Information was collected both retrospectively and prospectively on 499 HIV-1-positive patients enrolled in an ongoing national registry of patients with congenital coagulation disorders. Two methods were used to estimate each patient's seroconversion date: the mid-point between the last negative (either known or estimated) and the first positive test, and the median under a Weibull distribution, which was assumed to fit seroconversion data. The two methods of estimating the seroconversion time yielded similar results. The actuarial incidence of AIDS was estimated using the Kaplan-Meier survival analysis at 12.8% (95% confidence interval = 9.7-15.9) over 7 years for Italian haemophiliacs. Progression appears to be slow in the first 5 years after the infection, and to rise steadily thereafter. A strong association between faster progression and older age at seroconversion was found. Zidovudine-treated individuals seem to have a slower progression than untreated individuals, after controlling for CD4, but there was no association between progression and type and severity of the congenital disorder.

Acquired Immunodeficiency Syndrome↗

Transcranial Doppler (TCD) after nitroglycerin in migraine without aura.

Nitroglycerin, a vasodilating agent, was administered sublingually in migraine without aura patients and in healthy volunteers. Systolic, diastolic and time-mean flow velocity and pulsatility index, were measured by transcranial Doppler sonography in the major intracranial arteries before and after nitroglycerin administration. Following nitroglycerin administration, a significant decrease in systolic and time-mean velocity and pulsatility index was observed in migraine patients, whereas in control subjects only time-mean velocity decreased significantly. Based on those findings we hypothesize a more marked responsiveness to nitroglycerin in migraine patients as compared to healthy subjects.

Adult↗

Discriminant analysis of Hodgkin's disease and non-Hodgkin's lymphomas by age and serum proteins.

Immunonephelometric evaluations of 13 serum proteins were made in 71 patients with two types of lymphoproliferative diseases: Hodgkin's disease (32 patients) and non-Hodgkin's lymphomas (39 patients). The subjects were differentiated by discriminant analysis by means of age and three selected proteins: properdin factor B, IgM and ceruloplasmin. The results obtained permitted classification of 90% of the cases reported.

Adolescent↗

MIF-1 can accelerate neuromotor, EEG and behavioral development in mice.

Newborn mice were injected SC daily with 1 mg/kg of MIF-1 or saline during the first 19 days of life. The progress of each pup was monitored for physical (body weight, eye and ear opening), neurobehavioral (reflexes) and neurophysiological (EEG) development until the weaning stage. In early adulthood (40 days of age) mice were tested on a maze learning task. Results indicate that MIF-1 can accelerate neurologic (days 3-9), somatic (days 10-14) and electroencephalographic (days 16-19) parameters, and that the effects of treatment last into the early adult stage with increased learning abilities in an appetitive task.

Amino Acid Sequence↗

Chronic treatment with MIF-1 prevents the painful stimuli threshold elevation induced by neonatal handling in mice.

Chronic postnatal stressful handling results in a hyposensitivity to thermal nociceptive stimuli. This phenomenon is strongly affected by manipulations of the opioid system. In the present experiment, we report that chronic treatment with MIF-1 during the neonatal period prevents the behavioral alterations induced by handling while it is completely ineffective if injected acutely before antinociceptive testing by the tail flick test at 45 days of life.

Amino Acid Sequence↗

Problems of test choice and data analysis in behavioral teratology: the case of prenatal benzodiazepines.

Higher-tier tests for the assessment of early treatment effects should be aimed at providing specific information on the behavior processes affected, rather than simply at extending the descriptive data base. The contrast between positive and negative results can be useful to point out possible mechanisms of action. For example, late prenatal oxazepam exposure of mice produced a reduction of the amphetamine hyperactivity at the end of the second postnatal week, but did not significantly affect the response to scopolamine at the end of the third week. An impairment of active locomotor avoidance was observed at the young adult stage, which contrasted with the absence or scarcity of changes in passive avoidance and extinction responding in the same go-no go tests. These changes in response-activating mechanisms appear to be in agreement with the medium- and long-term effects on CNS monoamine metabolism described in the literature. As concerns statistical analysis, dichotomous or polytomous data obtained, e.g., by the Fox battery are not yet amenable to an adequate processing, due to the shortcomings of the available nonparametric tests. By contrast, mixed-model ANOVAs can cope with complex data obtained, e.g., in activity and learning tests. However, the available checks on various assumptions (normality, homogeneity of variance, sphericity) are not valid when nested factors, block factors and repeated measures coexist. Finally, the more usual cross-fostering procedures provide adequate information on some aspects (e.g., separation of main effects of prenatal treatments from postnatal maternal effects) but not on others.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Development of GABAergic modulation of mouse locomotor activity and pain sensitivity after prenatal benzodiazepine exposure.

Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. Locomotor activity (single 30-min session in a Varimex apparatus), hot-plate responding, and muscimol (GABAa agonist) effects thereon [see normative data in (16)] were assessed on postnatal day 14, 21, or 28. Prenatal oxazepam did not affect the development of hot-plate responding and muscimol analgesia; however, it reduced activity on day 14 (as in previous studies) and modified the profile of muscimol effects at 21 days (time of first appearance of an adult-like pattern of activity) and at 28 days. Specifically, oxazepam mice showed a faster recovery from the initial depression after 1 mg/kg of muscimol at the former age and a lack of rebound hyperactivity at the latter age. These effects might be explained either 1) by an accelerated development of GABAergic regulatory mechanisms, or 2) by the same monoaminergic system changes which can account for other effects of prenatal BDZ exposure (1,3). In any event, the dissociation phenomena found in the present study strengthen the notion that GABAergic influences contribute to the modulation of locomotor activity and of pain reactivity by mechanisms which are at least in part separate from each other (16).

Analysis of Variance↗

Prenatal oxazepam effects on cocaine conditioned place preference in developing mice.

The positively reinforcing and activity enhancing effects of IP cocaine (0, 5, or 25 mg/kg) were assessed at three ages (14-17, 21-24, and 28-31 days) in outbred CD-1 mouse pups treated prenatally by either oxazepam (OX, 15 mg/kg PO twice/day on days 12-16 of pregnancy) or vehicle (VEH). A 4-day unbiased conditioned place preference (CPP) procedure was used with combined visual and tactile cues (white walls and wide-mesh metal floor versus black walls and narrow-mesh floor). A single 25 mg/kg cocaine dose produced CPP in both prenatal groups of 28-31 day-old mice. At the two younger ages, a significant cocaine CPP was found in prenatal OX mice but not in vehicle animals; the latter apparently developed CPP less readily than the offspring of indisturbed dams in a previous experiment. On the other hand, prenatal OX did not produce substantial changes in the developmental profile of cocaine effects on locomotor activity, consisting of a dose-related response enhancement which is much more marked at 22 and 29 days than before weaning.

Aging↗

Long-term effects of acute perinatal asphyxia on rat maternal behavior.

In this study we used a rat model of graded perinatal asphyxia to study the long-term consequences of this manipulation on rat maternal behavior at adulthood. Rats were delivered by cesarean (C) section and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 0 (controls) or 20 min (asphyxia). Subsequently, female pups were given to surrogate mothers, weaned at 21 days postnatally and then left undisturbed until adulthood, when they were mated. Once they gave birth, on postnatal days (Pnds) 1, 3, 5, 7, 9, 11 and 13 they were observed in the home cage five times per day to assess their maternal behavior in an undisturbed condition. In addition, maternal behavior was observed for 30 min in a novel cage on Pnds 4 and 8. Perinatal asphyxia affected maternal behavior in the home cage, hypoxic females being more often found outside the nest area and performing more often behaviors such as self-grooming. Principal component analysis confirmed a more 'active' behavioral profile for hypoxic females. Hypoxic mothers were characterized by a longer latency to perform on-nest behavior and by a reduced frequency of pup retrieval and licking in the novel cage. No significant differences in corticosterone secretion in response to an acute stressor were found in dams belonging to the different treatments or in the body weights of the offspring. These results are suggestive of an arousal deficit due to perinatal hypoxia and point to the dopaminergic system as a potential neurochemical target for an early hypoxic insult.

Age Factors↗

Effects of prenatal AZT on mouse neurobehavioral development and passive avoidance learning.

Recent evidence has shown that perinatal administration of zidovudine (AZT) to HIV-infected mothers reduces the risk of maternal-infant transmission of the virus. Treatment of pregnant seropositive women with AZT is becoming a common medical practice, despite the paucity of information about the potential neurotoxic/behavioral-teratogenic effects of AZT on the developing organism. The aim of the present study is to evaluate in mice the short-, medium-, and long-term effects of prenatal exposure to AZT on neurobehavioral development. Pregnant mice were given 0.2, 0.4, and 2.0 mg/ml AZT in drinking water from day 10 of gestation to delivery. Offspring's viability was severely affected in the 2.0 mg/ml AZT group. Thus, behavioral analysis was carried out in offspring of 0.2 and 0.4 mg/ml AZT-treated females only. Some limited but significant alterations were found, such as stunted body weight, delayed appearance of the pole-grasping reflex, and a slight impairment in the acquisition phase of a passive avoidance response. Moreover, sexual differences in some items of the social behavior repertoire appeared to be affected by AZT treatment.

Agonistic Behavior↗

Chlamydia pneumoniae infection in patients with acute coronary syndrome: a clinical and serological 1-year follow-up.

The role of Chlamydia pneumoniae infection in pathogenesis and prognostic stratification of patients with acute coronary syndromes is still unclear. However, a limitation of many studies is the evaluation of the long-term prognostic role of a sample obtained during the acute phase, whereas the assessment of the temporal trend of antibody titers could be more useful. One-hundred and fourteen consecutive patients with acute coronary syndromes (71 with acute myocardial infarction and 43 with unstable angina) were studied. Blood samples were obtained immediately after hospital admission and 1, 3, 6 and 12 months after the acute event. The microimmunofluorescence test was used to detect C. pneumoniae specific antibodies. The incidence of new coronary events (death, myocardial infarction, recurrent angina) was recorded during the 1-year follow-up period. No significant difference was found between patients with (n = 35) or without (n = 79) new coronary events (N.C.E.) regarding baseline and serial values of C. pneumoniae antibodies. The rate of high titers at any time of follow-up was also similar in the two groups: IgG > or =1:512 were present in 52%, 64%, 55% and 32% of N.C.E.+ patients, and in 48%, 54%, 52% and 36% of N.C.E.- patients at 1, 3, 6 and 12 months respectively; IgA > or =1:256 were present in 26%, 23%, 30% and 23% of N.C.E.+ patients and in 20%, 30%, 25% and 19% of N.C.E.- patients at 1, 3, 6 and 12 months respectively. Our data indicate that elevated titers of C. pneumoniae antibodies, even with a serial 1-year evaluation, are not a predictor of future coronary events in patients with acute myocardial infarction or unstable angina.

Angina, Unstable↗

The impact of antiviral therapy with zidovudine: a retrospective study on HIV-positive hemophiliacs in Italy. Italian Group of Congenital Coagulopathies.

BACKGROUND: The effects of zidovudine (ZDV) treatment on progression to AIDS are not completely clear. This study evaluated the effects of ZDV treatment on the progression to AIDS in HIV-positive hemophiliacs. METHODS: A retrospective study was carried out on HIV-infected hemophiliacs: it included 238 individuals, 119 each from the treated and the non-treated groups. For the group receiving ZDV, we included those for whom a CD4+ count was available prior (median = 1 month) to beginning therapy. The cumulative incidence of developing AIDS was estimated by the Kaplan-Meier method. To identify factors independently associated with progression to AIDS, a Cox proportional hazards model was used. RESULTS: The cumulative incidence of developing AIDS at 8 years after HIV seroconversion was 10.4% [standard error (SE) = 2.8%] for the treated group and 17.1% (SE = 3.8%) for the non-treated group. The difference was statistically significant (p = 0.01). By multivariate analysis, ZDV therapy and CD4+ T-cell count > 200/mm3 were the parameters independently associated with a slower progression to AIDS. CONCLUSIONS: Treatment with zidovudine seems to slow the progression to AIDS in HIV-positive hemophiliacs.

Acquired Immunodeficiency Syndrome↗