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Biomedical subjects

M Pontecorvo

Publications and source records attributed to M Pontecorvo.

15 recordsLinked to original sources
PubMed1993

Effects of the selective sigma receptor ligand, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), on behavioral and toxic effects of cocaine.

Certain sigma receptor ligands have been shown to block locomotor stimulation produced by cocaine at doses that do not have significant behavioral activity when given alone. Using a potent and selective ligand of sigma binding sites, 6-[6-(4-hydroxypiperidinyl)hexyloxy]-3-methylflavone (NPC 16377), we further investigated the influence of sigma ligands on additional behavioral and toxic effects of cocaine in mice. A behaviorally inactive dose of NPC 16377 shifted the dose-effect function for the locomotor stimulant effects of cocaine to the right by a factor of 2.5. A higher dose of NPC 16377 produced an insurmountable blockade of this stimulant effect of cocaine. Prior exposure to cocaine enhances the locomotor stimulant effects of cocaine (sensitization). NPC 16377 prevented the development of cocaine sensitization without producing behavioral effects of its own. However, NPC 16377 was unable to block the expression of sensitization in mice previously exposed to cocaine. NPC 16377 also did not consistently alter the discriminative stimulus effects of cocaine or methamphetamine in rats discriminating either 3 or 10 mg/kg of cocaine, or 1 mg/kg of methamphetamine from saline. The potential phencyclidine-like behavioral effects of NPC 16377 were also evaluated. Unlike the NMDA channel ligand, dizocilpine, NPC 16377 did not increase responding under a fixed-interval schedule of food presentation in rats nor did it substitute for the discriminative stimulus effects of either 1.5 mg/kg of phencyclidine or 0.2 mg/kg of dizocilpine in rats discriminating these drugs from saline. NPC 16377 displayed limited but significant anticonvulsant activity against diazepam-sensitive cocaine convulsions. The lethal effects of higher doses of cocaine were neither significantly blocked nor enhanced in rats or mice with NPC 16377. These findings extend earlier observations on the cocaine-blocking effects of sigma ligands to a novel structure with exceptional selectivity for sigma sites. These data indicate that some sigma ligands may be capable of altering certain behavioral and toxic actions of cocaine without notable behavioral side effects as evidenced in preclinical tests. As such, these compounds may ultimately be useful in the treatment of cocaine abuse.

Animals↗
PubMed1985

Selective memory loss following nucleus basalis lesions: long term behavioral recovery despite persistent cholinergic deficiencies.

Rats were trained for several months to perform a radial arm maze task and then given either sham or ibotenic acid lesions of the nucleus basalis magnocellularis (NBM), the primary cholinergic projection to the neocortex. The lesion produced a profound and apparently selective disturbance in memory for recent events. Further testing revealed that although the memory deficit persisted for several weeks, a gradual but complete recovery eventually occurred. Moreover, when these functionally recovered rats were later tested on a passive avoidance task that is normally sensitive to lesions of the NBM, no deficit was found. Thus, the post-lesion recovery of function generalized to a different memory test, upon which no post-lesion practice had been given. Post-mortem determinations revealed that the lesions caused marked neurodegeneration of the NBM, and decreases in both cortical choline acetyltransferase activity and high affinity choline uptake, but had no effect on density of muscarinic receptors. No evidence of neuronal recovery or neurochemical compensatory changes in the cholinergic system was found in the cortical projection areas, lesion site, or in parallel cholinergic systems terminating in the hippocampus or olfactory bulb. These results support the idea that the cortically-projecting cholinergic cells of the NBM normally play an important role in mediating recent memory. However, they also demonstrate that any simple relationship between the function of this brain region and the mediation of recent memory is unlikely. Finally, the results of this study direct attention toward issues related to the mechanisms involved with the recovery of function, and the extent to which degeneration of this brain area may contribute directly to the severe disturbance of cognitive function associated with certain neurodegenerative diseases (e.g., Alzheimer's, Pick's and Parkinson's disease).

Alzheimer Disease↗
PubMed1980

[Anti-tetanus vaccines, serums and immunoglobulins].

Specific immunity to tetanus toxin is only artificially acquired and is provided by the presence in the blood and in the extravascular fluids of an IgG antibody passively administered or actively produced by the organism through vaccine injections. In the first case serum of human origin is now preferred to serum of animal origin due to the lack of major undesirable reactions and longer duration of protection (about 4 weeks versus 7-10 days). Tetanus toxoid is one of the most safe and potent known immunogens. For primary immunization adsorbed toxoid is given on two occasions at 2 months interval with a third reinforcing dose approximately one year after the second. The subsequent antitoxin response persists at protective level for at least 5 years and for a longer time (10 years about) after a booster. The ability to promptly react to a booster injection (immunological memory) is greatly long-lasting in persons who have previously received at least two doses.

Antibodies↗
PubMedDate not supplied

[Antibody response in humans to A/New Jersey/76 influenza vaccine (author's transl)].

74 adults 25 to 50 years old have been immunized with a sigle dose of three different influenza vaccines, namely: 1. Bivalent A and B (A/Victoria/75 600 IU; B/Hong Kong/73 300 IU); 2. Monovalent A/New Jersey/76 400 IU, and 3. Trivalent (A/Victoria/75 300 IU; B/Hong Kong/73 300 IU; A/New Jersey/76 300 IU). Reactions were insignificant or trivial. One month later antibody content was measured in the blood and satisfactory reponses were observed in bivalent and monovalent vaccines treated groups. Less satisfactory reponse was observed in the trivalent vaccine group, probably according to the lesser antigenic content in A/Victoria and A/New Jersey strains.

Adult↗
PubMedDate not supplied

Outcome measures for the study of activities of daily living in vascular dementia.

Decline in functional abilities is a major component of the dementia syndrome. The definition of dementia in the International Classification of Diseases (10th rev.) requires a cognitive impairment sufficient to impair personal activities of daily living (ADL). The Diagnostic and Statistical Manual of Mental Disorders (4th ed.) also requires cognitive deficits sufficiently severe to cause impairment in occupational or social functioning and must represent a decline from a higher level of functioning. However, the term disability is more appropriate than impairment to describe a loss in activities, as opposed to a loss of elementary functions, and is consistent with World Health Organization definitions of impairment, disability, and handicap. There is no doubt that ADL outcomes are required in therapeutic drug studies on vascular dementia, and there is a good rationale and some evidence for the use of ADL scales developed for therapeutic research in Alzheimer disease, favoring scales devoid of items sensitive to physical disabilities. Similarly, ADL-related clinical milestones could be used for longer-term studies aiming predominantly at slowing progression of disease in both early and later stages of dementia. Slower decline in ADL and delay in reaching ADL-related clinical milestones should be considered as valid outcomes by regulatory bodies in the process of dementia drug approval.

Activities of Daily Living↗