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Biomedical subjects

S Genedani

Publications and source records attributed to S Genedani.

At least 55 records · Page 3Linked to original sources

Behavioral activity and active avoidance learning and retention in rats neonatally exposed to painful stimuli.

Twice daily for the first 15 days after birth, rats from the same litters were either placed for 5 sec on a hot plate (55 degrees C) (treated group), or on a plate maintained at body temperature (38 degrees C) (manipulated group). Controls were left undisturbed. When 90 days old, they were studied for pain threshold, open-field behavior, and two-way active avoidance learning and retention. Weight gain, pain threshold, open-field behavior, and active avoidance retention were not significantly different in the three groups. On the other hand, the rate of two-way active avoidance learning was significantly greater in treated rats. These results suggest that repeated neonatal exposure to painful stimuli, in rats raised under otherwise normal conditions, improves later active avoidance performance. The most likely mechanisms are discussed.

Acoustic Stimulation↗

Effect of polyamines on perfused rat heart contractility.

The influence of polyamines (putrescine, spermidine and spermine) on heart contractility was studied using perfused rat ventricle strips (2 X 10 mm), electrically driven at 1 Hz. Putrescine (100 microM) caused a negative inotropic effect gradually increasing in intensity, whereas spermidine and spermine (10 and 100 microM) caused a sharp, positive inotropic effect, followed by a rapid and more marked fall. The possibility that these effects of polyamines on heart contractility may be due to their role in Ca++ fluxes and mobilization, and in membrane functions, is discussed.

Animals↗

Convulsive syndrome induced by the intracerebroventricular injection of alpha-difluoromethylornithine in rats.

In adult rats, the intracerebroventricular injection of alpha-difluoromethylornithine (DFMO), a polyamine antimetabolite which specifically inhibits ornithine-decarboxylase, induces a typical convulsive syndrome (ED50 = 100 micrograms/rat) and death (LD50 = 300 micrograms/rat). Histological lesions are seen only with the highest doses and are essentially restricted to the Ammon's horn neurones. Since DFMO is currently undergoing clinical trials for use in cancer chemotherapy, including brain tumours, its CNS toxicity should be carefully considered.

Animals↗

Putrescine has analgesic activity, in rats.

Putrescine, intraperitoneally injected into rats at doses of 200, 300 and 400 mg/Kg, had a dose-dependent analgesic effect (hot plate, 55.5 degrees C), which was not antagonized by naloxone. Analgesia was also obtained by intracerebroventricular injection (1,000 nmoles/rat). Chronic administration (300 mg/Kg/day i.p. for 8 consecutive days) resulted in the development of tolerance. In our experimental conditions, no obvious toxicity was observed. These results may suggest for polyamines a role in nociception, and may disclose a new class of analgesic drugs.

Analgesics↗

Effect of alpha-difluoromethylornithine (DFMO) on the behavioral syndrome induced by intracerebroventricular injection of ACTH 1-24, in rats.

Stretching-yawning syndrome (SYS) and penile erections (PE) are typical components of the behavioral picture induced by intracerebroventricular (i.c.v.) injection of ACTH 1-24. The present study shows that pretreatment with alpha-difluoromethylornithine (DFMO), and irreversible inhibitor of mammalian ornithine decarboxylase (ODC), antagonizes these behavioral effects in a dose-dependent way, in rats. These results suggest that ODC and polyamines may play a role in the transduction and transmission of receptor-mediated signals.

Adrenocorticotropic Hormone↗

Sex-linked differences in avoidance learning in the offspring of rats treated with nicotine during pregnancy.

The offspring of rats treated with nicotine (0.5 mg/kg/day SC) on days 1-20 of gestation, were trained for active avoidance conditioning when 60 days old. Although learning was similar in both control groups of males and females, nicotine exposure during fetal life improved learning in females but reduced it in males, the difference between these two groups being statistically significant from day 17 until the end of the training period (day 25).

Aging↗

Oxolinic acid--trimethoprim combination: effects on DNA synthesis and on viability of Escherichia coli.

The synergistic bactericidal effect of the oxolinic acid-trimethoprim combination has been confirmed on an exponentially growing strain of Escherichia coli, and is paralleled by a synergistic inhibition of 14C-uracil incorporation into the bacterial DNA. These data provide experimental support for the postulate that the synergistic effect of quinolone-trimethoprim combinations, observed both in vitro and in vivo, is due to a complementary blockade of bacterial DNA synthesis.

DNA, Bacterial↗

Microbiological and pharmacological evaluation, in mice and rats, of a new nitrofuran: 2-amino-4-methyl-6-(2-ethinyl-5-nitrofuryl)-pyrimidine (nifurpyrimidine).

2-Amino-4-methyl-6-(2-ethinyl-5-nitrofuryl)-pyrimidine (nifurpyrimidine) is a new furan derivative. Its spectrum of activity is wide and includes both gram-positive and gram-negative microorganisms and fungi; moreover, it inhibits the growth of multiple-drug resistant salmonellae. The minimal inhibitory concentrations ranged from 0.25 to 10 microgram/ml. Resistance was developed in vitro in a step-wise manner and was partially reversed after 7-10 passages in drug-free media. The pharmacological study of the drug was carried out in rats and mice and gave the following results: (1) no acute toxicity was demonstrable following oral administration; (2) no intestinal absorption occurred and virtually the whole dose of nifurpyrimidine administered by oral route was recovered in the intestinal content; (3) the presence of urine, plasma or feces did not modify the antibacterial activity of the compound.

Animals↗

Behavioural effects of naloxone in rats.

Naloxone in rats induces a behavioural syndrome closely resembling that induced by intraliquorally injected ACTH peptides. This effect is probably due to a displacement of the ACTH peptides from other receptors (e.g. opiate receptors).

Animals↗

ACTH(1-24) stimulates the migration of human monocytes in vitro.

In view of the increasing evidence that a variety of stresses can influence immune responses, the direct effect of adrenocorticotropic hormone on the migration of human monocytes was studied in vitro. ACTH(1-24) significantly increased the number of migrating cells when placed in the same or the opposite compartment of the chemotaxis chamber, maximum activity being obtained at 10(-14) and 10(-8) M. The results indicate that ACTH(1-24) directly and potently stimulates the migration of human monocytes by means of a chemokinetic effect.

Adrenocorticotropic Hormone↗

Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives.

The present paper deals with a fundamental issue in neuroscience: the inter-neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume transmission. There exist two competing theories on inter-neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter-neuronal communication in the brain, the volume and wiring transmission concept that to a great extent reconcile these two theories. Thus, the theory of volume and wiring transmission are summarized and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network theory is reminiscent of the old reticular theory of Apathy. Finally, the so-called 'tide hypothesis' for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. Early indirect evidence supporting volume transmission in the brain was the discovery of transmitter-receptor mismatches. Thus, as an experimental part of the present paper a new approach to evaluate transmitter-receptor mismatches is given and evidence for inter-relationships between temperature micro-gradients and mismatches is provided.

Cell Communication↗

Development and behavioral outcomes of perinatal inhibition of ornithine decarboxylase.

Rats were treated with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), at a dose of 200 mg/kg/day SC, either prenatally (to the mothers, on days 16 to 20 of gestation) or neonatally (to the pups, on days 1 to 10 after birth). At this dose level neither maternal reproductive performance (prenatal treatment) nor gain in body weight on the part of offspring were affected. Earlier developmental alterations were rapidly overcome. Prenatally-treated rats proved less active than controls in the open field, performed better in passive avoidance retention (both preweaning and postweaning), and had a shorter post-ejaculatory interval in the male copulatory test. Postnatally-treated rats performed better than controls in two-way active avoidance conditioning, and in passive avoidance retention (as adults). Reproductive performance of the treated female offspring was similar to that of controls. ODC activity in brains of DFMO-exposed offspring was substantially inhibited throughout treatment (-72 to -41%, compared with respective controls), but showed a strong rebound after termination of treatment (up to +400%, compared with respective controls). These results show that partial inhibition of ODC activity during a limited period of the perinatal life has no adverse effect on the overall behavioral development of rats: indeed, some performances are actually improved. This being the most likely due to a rebound ODC hyperactivity after termination of treatment, when brain maturation is still in progress.

Animals↗

Effects of prenatal exposure to cigarette smoke and nicotine on pregnancy, offspring development and avoidance behavior in rats.

Pregnant rats were exposed to cigarette smoke or injected with nicotine twice daily on days 1 to 20 of gestation. In the smoke-exposed rats, weight gain during pregnancy was significantly reduced. On the other hand no significant effect was observed on delivery rate, litter size, weight of offspring, percent weight of the brain, number of dead fetuses, offspring mortality during lactation and ratio of males to females. No gross malformation was detected. The offspring were trained for avoidance conditioning when 60 days old: the number of rats satisfying the criterion of learning at the end of conditioning was quite similar in the three groups, but the rate of avoidance acquisition was significantly greater in the offspring of the dams exposed to cigarette smoke.

Animals↗