No abstract

Although considered to be generally safe, a number of beta-lactam antibiotics have been associated with epileptic seizures in humans. Furthermore, some beta-lactam antibiotics, including ceftriaxone, are used to evoke convulsions under experimental conditions. Recently it was demonstrated that ceftriaxone increased expression of the glutamate transporter (GLT1) and its biochemical and functional activity in the brain of rodents. GLT1 regulates extracellular concentrations of glutamate, an excitatory amino acid involved in the pathogenesis of seizures and epilepsy. Because of its rapid transfer of glutamate into neurons and adjacent glial cells, GLT1 diminishes glutamate toxicity. We investigated whether ceftriaxone (200 mg/kg body wt) administered intraperitoneally (ip) for 6 days could modify the convulsant effects of pentylenetetrazole (PTZ, 100 mg/kg ip) in inbred male BALBcAnNCR and C57 black (BL)/6 mice aged 4 and 12 weeks. Ceftriaxone pretreatment provided significant protective effects against PTZ-evoked generalized clonic convulsions (GCCs), generalized clonic-tonic convulsions (GCTCs), and convulsion-induced mortality during a period of 30 mins after PTZ administration. The incidence of GCCs, GCTCs, and death was statistically significantly lower for BALBcAnNCR mice of both ages, particularly younger mice. The latency time for each of the three parameters was significantly greater, with the exception of GCCs in adult mice. Protective effects of ceftriaxone were also noticed in adult C57BL/6 mice but not in prepubertal C57BL/6 mice. This is the first demonstration of anticonvulsant effects of ceftriaxone or any other beta-lactam antibiotic, which are not uniform across the mouse population. Our results provide new insight into the effects of ceftriaxone, which need further investigation.

Chromosomal alterations are a feature of both aging and Alzheimer's disease (AD). This study examined if premature centromere division (PCD), a chromosomal instability indicator increased in AD, is correlated with aging or, instead, represents a de novo chromosomal alteration due to accelerating aging in AD. PCD in peripheral blood lymphocytes was determined in sporadic AD patients and gender and age-matched unaffected controls. Metaphase nuclei were analyzed for chromosomes showing PCD, X chromosomes with PCD (PCD,X), and acrocentric chromosomes showing PCD. AD patients, regardless of age, demonstrated increased PCD on any chromosome and PCD on acrocentric chromosomes in both genders, whereas an increase in frequency of PCD,X was expressed only in women. This cytogenetic analysis suggests that PCD is a feature of AD, rather than an epiphenomenon of chronological aging, and may be useful as a physiological biomarker that can be used for disease diagnosis.

This study tested the question of whether executive failure associated with frontal lobe deficit is associated with, and therefore, may influence declarative memory dysfunction in Parkinson's disease (PD). A variety of memory and 'frontal sensitive' tasks were used. The 'frontal lobe dysfunction' hypothesis was tested in part, by examining the serial position effects (SPE) of word list learning across five successive trials. The relationship between memory and 'frontal sensitive' task scores was tested also. A total of 39 PD patients early in the course of the disease and 31 matched controls were included in the study. The PD subjects showed mild memory deficits in comparison to the healthy control group. In the face of any hypothesized selective 'dysexecutive' syndrome in PD group, the latter groups learning strategy across five trials did not differ from that of the control group. Also, the expected interrelation between memory and 'frontal sensitive' scores was not obtained. Therefore, the hypothesis that frontal dysfunction alone may account for memory impairments in PD is not fully supported.

Auditory event-related potentials were recorded in demented, drug-free patients with Huntington’s disease and Alzheimer’s disease, as well as in demented and nondemented patients with Parkinson’s disease, who were matched for age, duration and stage of the disease. The normal P3 latency at a given age was predicted by using an age regression equation that had been calculated on the basis of the findings in 42 normal adults. Using this procedure, a prolonged P3 latency was found in about two thirds of demented patients, irrespectively of the underlying disease. Although the prolonged P3 latency proved to be useful electrophysiological correlate of dementing illness, no differences were found between the observed groups in respect to other components of the auditory event-related potentials (N1 and P2).