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Biomedical subjects

L Durelli

Publications and source records attributed to L Durelli.

88 records · Page 5Linked to original sources

Carbamazepine toxicity and poisoning. Incidence, clinical features and management.

Carbamazepine is the drug of first choice in the treatment of simple and complex partial seizures and trigeminal and glossopharyngeal neuralgias. It is usually preferred to phenobarbitone or phenytoin because of its powerful antiepileptic activity combined with a relative lack of adverse effects. In this article the mechanisms of action and pharmacological properties of carbamazepine are outlined in order to explain the pathogenesis of most side and toxic effects. Most of these effects, namely those affecting the nervous or cardiovascular systems, correlate well with an increased concentration of the drug in plasma and disappear spontaneously upon discontinuation of therapy. Other, less frequent toxic effects, namely aplastic anaemia or fatal hepatitis, may be ascribed to unforeseeable idiosyncratic reactions. Carbamazepine poisoning, usually accidental and sometimes secondary to the coadministration of other drugs, yields a clinical picture with neurological and cardiovascular signs. The outcome is usually favourable, sometimes with spontaneous improvement, and death is a distinct rarity. No specific antidotes are available. The oral administration of activated charcoal has been shown to be an effective therapeutic measure significantly reducing the plasma half-life of the drug.

Animals↗

[Preventive anti-epileptic action of taurine administered by direct cortical perfusion].

To test taurine preventive antiepileptic effect a 90-minute taurine cortical perfusion was made to 8 cats in the left sensory-motor area. A cobalt lesion was then made in the same area following routine. In all cats the beginning and subsequent development of the interictal and ictal epileptic picture were remarkably delayed in comparison with a control group of animals without taurine pretreatment. The taurine preventive action, as the consequence of its brain uptake, is discussed in comparison with the lack of taurine preventive action, when administered intraperitoneally (MUTANI et al., in press). The possibility of the taurine uptake by the normal brain and, therefore, of the prevention of the epilepsy would be related to the different anatomo-physiologic features of the barriers met in the two routes of administration.

Animals↗

[Antagonism between focal epilepsy and taurine administered by cortical perfusion].

The therapeutic action of taurine cortical perfusion was tested in cats affected with Premarin and cobalt cortical epileptogenic foci. In all animals taurine provoked the disappearance of EEG epileptic abnormalities. In the case of Premarin focus the effect appeared more quickly than in the cobalt one. This different time-course, according to previous reports on the antiepileptic action of the parenteral administration of the amino acid, suggests the hypothesis of a taurine direct inhibitory action against Premarin focus and, on the contrary, a mediated action towards the cobalt's. The latter might be related to the metabolic production of some taurine derivative.

Animals↗

Multiple sclerosis. I. The immune pathogenetic hypothesis.

Animal models indicate that chronic relapsing demyelinating diseases of the central nervous system (CNS) can be induced both by certain viruses and by sensitization to myelinic antigens. Epidemiological data (studies on emigrants and on so-called "Multiple Sclerosis (MS) epidemics") suggest that an environmental transmissible agent, acting on a genetic substrate, could play a role in the pathogenesis of the disease. The transmissible agent could be a virus. Data to this effect are insufficiently indicative, but the hypothesis has been recently put forward that it could be antigenically related to the lymphotropic viruses (HTLV). The transmissible agent could act either by desegregating myelinic antigens or by inducing an alteration of the immune system with a reduction of T lymphocyte suppressor activity. There appears to be rapid and intense activated T lymphocyte "traffic" across the blood-brain barrier in patients affected with MS. Cells specifically sensitized to the unknown antigen find within the CNS other cells able to perpetuate presentation of the antigen (HLA-DR+ astrocytes and endothelial cells, not present in normal brain) and then activate the macrophages which in turn begin immuno-mediated phagocytosis of the healthy myelin. Aspecific immune cells are also recruited into CNS where seem to abnormally proliferate (possibly owing to reduced suppressor activity) producing antibodies against various viral or cerebral antigens which are not clearly related to the pathogenesis of the disease (production of intra-CNS "nonsense" antibodies and synthesis of the oligoclonal immunoglobulin bands seen at the cerebrospinal fluid electrophoresis.)

Antibodies, Monoclonal↗

Multiple sclerosis. II. A critical assessment of immunotherapy.

The profound changes undergone by the immune system in Multiple Sclerosis (MS) suggest that any therapeutic protocol should take immunosuppressive therapy into consideration. The results of the numerous clinical trials should be assessed extremely cautiously in the light of the variable and unpredictable course of MS. Immunosuppressive therapies may act specifically by inhibiting a certain stage in the immune response, or, by contrast, by inducing an overall inhibition of the immune system. Low dosage, aspecific immunosuppressive therapeutic protocols with corticosteroids or azathioprine are used routinely, although there is no sure evidence of their effects. There are, however, unquestionable data on the numerous (and serious) side effects. High dosage, aspecific immunosuppression appears to be better tolerated (probably due to the brevity of the therapies) and to have certain immunodepressant effect within the CNS. ACTH and methylprednisolone are recommended for short-term relapse therapy. Research work on high dosage cyclophosphamide and total lymphoid irradiation is still too limited. Specific immunosuppressive treatment will no doubt be part of future autoimmune disease therapy, but for the time being is no more than theoretically stimulating experimentation (antiidiotypic monoclonal antibodies, specific T cell suppressor factor, T cell "vaccination"). Important multicentric studies on Cyclosporin-A and Copolymer 1 are almost complete once again without reassuring data and with documentation on the numerous side effects as regard to Cyclosporin-A. Clinical trials with Beta-interferon are still in progress and, so far at least, this drug appears to be characterized by the absence of important side effects.

Adrenocorticotropic Hormone↗

[Anticonvulsant action of pargyropyranone in various models of experimental epilepsy in the cat].

The new anticonvulsant drug pargypiranone was studied in different models of experimental epilepsy in cat (penicillin and Premarin cortical focus, cobalt cortical focus, penicillin generalized epilepsy). The drug proved to possess a strong anticonvulsant effect upon focal electroclinical phenomena and a poor effect on penicillin generalized epilepsy. It seems probably that pargypyranone has a valid effect on partial epileptic seizures.

Animals↗