Polydeoxyribonucleotide (defibrotide) protects against post-ischemic behavioral, electroencephalographic and neuronal damage in the gerbil.

The effectiveness of defibrotide, a single-stranded polydeoxyribonucleotide compound, in preventing damage caused by cerebral ischemia was studied. Global ischemia was induced in anesthetized gerbils by bilateral carotid artery occlusion for 10 min. Defibrotide (100 mg/kg) or saline was injected, i.v., immediately after reperfusion. The following parameters were evaluated simultaneously: (1) electroencephalographic (EEG) spectral power, recorded before, during and after the ischemic period; (2) body temperature, monitored with a rectal thermistor probe after reperfusion for 120 min; (3) spontaneous motility, evaluated through a photocell system and quantified in terms of total distance travelled in 30 min, 1 h after recirculation and at periods over 15 days; (4) mnemonic functions assessed by passive avoidance test from 3 to 15 days after ischemia; (5) histological examination, 7 days after reperfusion, counting CA1 hippocampal neuronal cells. The ischemia-induced complete flattening of spectral power was significantly reversed (P < 0.01) by post-ischemic treatment with defibrotide between 30 and 90 min after ischemia. A complete recovery of total EEG spectral power was seen in the defibrotide group at 6 h and the saline ischemic group at 1 day. Seven days after bilateral carotid occlusion, there was a significant decrease in spectral power (-70% +/- 6) together with a loss of the number of CA1 cells in the saline ischemic group (-64%). Treatment with defibrotide significantly protected against the decrease in spectral power (-30% +/- 7) and cell loss (-9%). Finally, the number of animals found to be protected against the ischemia-induced flattening was significantly larger for defibrotide-treated gerbils than for saline-treated animals throughout the experiment except for the third day. Body temperature was significantly decreased only at 30 min after reperfusion in both ischemic and sham-operated groups. Defibrotide reduced ischemia-induced hypermotility but only 6 h after the insult. The ischemia-induced impairment of memory was partially reversed within 3 days in the defibrotide-treated animals and fully reversed within 7 days in the defibrotide group and 15 days in the saline group. Our results demonstrate that defibrotide, even when administered after the post-ischemic period, possesses anti-ischemic properties. The mechanism by which defibrotide protects the ischemic reperfused brain is still largely unknown. However, a neuroprotection via adenosine A1 and A2 subtype receptor interaction can be put forward.

EEG power spectra and behavioral correlates in rats given chronic morphine. Lack of residual long-term EEG and neuronal changes.

The short-term (during tolerance to behavioural effects and withdrawal) and long-term (3, 6, 9 and 12 months after treatment) effects of morphine on mean total electroencephalographic spectral power (analysed by means of fast Fourier transform) and band distribution (delta, theta, alpha, beta) were studied in freely moving young rats implanted with chronic cortical bilateral recording electrodes. Morphine was administered i.p. daily for 1 month at weekly increasing doses of 20, 50, 100 and 200 mg kg-1, and the electroencephalogram was evaluated for 2 h at every change of dose. Treatment with 20, 50 and 100 mg kg-1 led to a significant increase in mean total spectral power 30-60 min from treatment. However, the dose of 100 mg kg-1 led to a smaller increase than that obtained with 50 mg kg-1 and no change was shown with the highest dose, suggesting the progressive development of tolerance. The modification observed for 100 mg kg-1 was accompanied by a relative increase in the delta and decrease in the theta and alpha power spectra. Between the last day of morphine and the first 3 days of abstinence, a progressive decrease in mean total spectral power accompanied by a significant increase in delta and beta and a decrease in theta and alpha frequency was observed. Long-term EEG activity and the counting of the pyramidal cells of the hippocampus failed to reveal any pathological findings after 3, 6, 9 and 12 months.

Different kinetics of tolerance to behavioral and electroencephalographic effects of chlordiazepoxide in the rat.

The daily oral administration of chlordiazepoxide (40 mg/kg) over 9 weeks in rats elicited full tolerance to muscle relaxant effects within 7 weeks, as revealed by twice weekly evaluations of abdominal tone myorelaxation and decreased grip strength. No full tolerance was achieved, however, during the 9 weeks of treatment in terms of ataxia. Electroencephalographic (EEG) studies showed that this tolerance to the behavioural effects was accompanied by a progressive decrease in mean power spectra, associated with a progressive decrease in the beta band, but in this case, full tolerance was reached within 4 weeks. Once weekly evaluations of the ability of chlordiazepoxide to protect the animals against pentylenetetrazole seizures revealed a similar pattern. Treatment with flumazenil (50 mg/kg p.o.) 24 h after the last chlordiazepoxide administration induced a clear withdrawal syndrome associated with EEG changes which consisted of an increase in total power spectra associated with an increase in the delta band (in comparison with chlordiazepoxide-dependent rats not given the antagonist). These findings suggest that the different kinetics of the tolerance to anticonvulsant and EEG effects in comparison to myorelaxant effects can be attributed to a different involvement of benzodiazepine receptor subtypes.

[Coordination of aid to the elderly in the environment of a local community health unit in Lombardy. Organizational experiences]. / Il coordinamento dell'assistenza all'anziano nell'ambito di una unità socio-sanitaria locale della Lombardia. Esperienze organizzative.

A group of geriatric specialists retained their involvement after suppression of a geriatrics division as part of the Lombard Region's hospital plan. Reference is made to the geriatric orientation bestowed on a rehabilitation medicine division, the experiences of a geriatric out-patient department in a hospital, links with rest homes, the social services, the home care services, and family physicians. Updating, training and support activities that can be carried out to help domiciliary service workers are described, along with the support that can be given to rest homes, especially if they have no sheltered structures. Stress is laid on the possible coordination of aid to the elderly on the part of persons operating within a departmental rehabilitative structure.