ABSTRACT. The prediction, measurement, and monitoring of neurologic toxicity of antibacterial agents is an exceedingly difficult matter. In this study we investigated if in vitro exposure of cultured brain cells to antibacterial drugs could predict neurotoxicity in man. Effects of antibiotics used for therapy of bacterial CNS infections on growth and differentiation in dissociated rat brain cell cultures were studied over 24 days in culture, the drugs being added from 10 to 17 days in culture, the main differentiation phase of rat CNS cells. Our results demonstrated a reversible inhibition of cerebral sulfate transferase activity ( p < 0.001 or < 0.01) and to a lesser extent ( p < 0.001 or NS) of DNA synthesis in brain cell cultures by the highest concentrations studied of amikacin, cefuroxime, and ceftazidime which correspond to peak cerebrospinal fluid values attained by intraventricular therapy in patients. Accumulation of DNA reflects brain cell growth whereas cerebral sulfate transferase activity parallels brain cell differentiation. Our findings indicate that intraventricular therapy could be more toxic with amikacin, cefuroxime, and ceftazidime than with penicillin, chloramphenicol, or ceftriaxone. Thus, this brain cell culture model might become a supplement, complement, or even alternative technique for neurotoxicity assessment of antibiotics with proven or potential value for therapy of CNS infections. (Pediatr Res 24: 367-372,1988) Abbreviations BCC, brain cell culture CSF, cerebrospinal fluid DIC, days in culture CST, cerebral sulfate transferase reviews of case reports (1, 2). CNS toxicity is a well-described complication of intraventricular antibiotic therapy for gramnegative bacillary ventriculitis and CSF shunt infections (l,2,4-7). Animal toxicity tests bear a relatively poor predictive value for neurotoxicity in man and require the use of a high number of animals (4,5,(8)(9)(10). Therefore, back-shifting of neurotoxicity tests from the human or animal situation to a relatively simple and reproducible system in vitro was the principal aim of the present research.There are many reports presenting evidence of dose-dependent antiproliferative effects of various antibiotics on cultured eucaryotic cells. The cell types studied include human fibroblasts (1 1), bone marrow cells (12), and dissociated brain cells (1 3). As in vitro correlative of dose-related marrow suppression by chloramphenicol it was found several decades ago that this drug inhibits mitochondria1 protein synthesis not only in bacteria but also in proliferating bone marrow cells (14, 15). More recently, the inhibition of cell proliferation has most often been studied for the @-lactam antibiotics on cultured human myeloid percursor and lymphoid cells, the clinical consequences being neutropenia and impairment of cellular and humoral immune responses induced by 6-lactams (12, 16-1 8).The purpose of our investigation was to monitor the effects of antibiotics on growth and differentiation in dissociated rat BCC which might help to pred...

Oligodendrocytes were isolated from mixed glial cultures of neonatal mouse forebrain and further grown in serum-free hormone supplemented culture medium. Cell populations were identified by indirect immunofluorescence using a range of specific antibodies, revealing a predominantly immature population of oligodendrocytes, the majority expressing the myelin glycolipids galactocerebroside and sulfatide on their plasma membrane. Astroglial contamination was found to be minimal. Simultaneous autoradiography and immunofluorescence demonstrated the presence of a transport system for the major inhibitory neurotransmitter GABA in the oligodendrocytes. The transport system was found to be energy, sodium and temperature dependent. Kinetic analysis revealed a high affinity system, with a Km of 6.27 microM and Vmax of 0.714 nmol/min/mg protein, which is comparable to that found previously for CNS neurons and astrocytes.

Animal de fondo (1949), by Juan Ramón Jimenez, is an enigmatic and joyous recounting of a mystical trance which the poet experienced during a sea voyage from New York to Buenos Aires in 1948. This essay approaches the poems from the perspective of classic Hindu religious traditions. The conciencia frequently used by Juan Ramón to express integration with the natural world is analogous to Brahman, the all-pervading reality which for the Vedic poets includes everything from the life of man to sticks and stones. The apparent polytheism of Animal de fondo echoes Vedic hymns, which deify many important social and natural elements. The Hindu concept of dharma, the sacred law of society regulating moral order, duties, and forms of conduct appropriate for different classes or persons, appears in poems where the poet exults in his poetizing function. Juan Ramón assimilated elements of the relativist-pluralist Hindu tradition that relegated questions of dogma to secondary importance, and, like the Vedic hymn-makers, was able to capture religious reality that was reflected in his own heart and mind and affirm it joyously.

No abstract