Ammonia toxicity to the brain and creatine.

Symptoms of hyperammonemia are age-dependent and some are reversible. Multiple mechanisms are involved. Hyperammonemia increases the uptake of tryptophan into the brain by activation of the L-system carrier while brain glutamine plays a still undefined role. The uptake of tryptophan by the brain is enhanced when the plasma levels of branched-chain amino acids competing with the other large neutral amino acids are low. Hyperammonemia increases the utilization of branched-chain amino acids in muscle when ketoglutarate is low, and this is further enhanced by glutamine depletion (as a result of therapy with ammonia scavengers like phenylbutyrate). Anorexia, most likely a serotoninergic symptom, might further aggravate the deficiency of indispensable amino acids (e.g., branched-chain and arginine). The role of increased glutamine production in astrocytes and the excitotoxic and metabotropic effects of increased extracellular glutamate have been extensively investigated and found to differ between models of acute and chronic hyperammonemia. Using an in vitro model of cultured embryonic rat brain cell aggregates, we studied the role of creatine in ammonia toxicity. Cultures exposed to ammonia before maturation showed impaired cholinergic axonal growth accompanied by a decrease of creatine and phosphocreatine, a finding not observed in mature cultures. By using different antibodies, we have shown that the phosphorylated form of the intermediate neurofilament protein is affected. Adding creatine to the culture medium partially prevents impairment of axonal growth and the presence of glia in the culture is a precondition for this protective effect. Adequate arginine substitution is essential in the treatment of urea cycle defects as creatine is inefficiently transported into the brain

ULF/ELF electromagnetic fields produced in a conducting medium of infinite extent by linear current sources of infinite length

A previous analysis of a linear current source of finite length embedded in a conducting medium of infinite extent is extended to linear current sources of (1) infinite length and (2) semi-infinite length. Electric and magnetic field expressions are derived, and the results are numerically evaluated for frequencies in the ULF/ELF bands. For convenience, some of the results are presented in a dimensionless form. A comparison is made between the electromagnetic fields produced by linear current sources of finite and infinite length, and it is shown that there is a relative enhancement in the electric field near the source of finite length. It is also found that an optimum frequency exists for the electric field produced by a linear current source of infinite length at which the field amplitude is a maximum at a fixed observation point. Some practical applications of our results are suggested

ULF/ELF electromagnetic fields generated along the sea floor interface by a straight current source of infinite length

Propagation of ULF/ELF electromagnetic fields along the seafloor interface (assumed to be a plane boundary separating two semi-infinite conducting media) is considered. Earlier expressions for the electromagnetic fields generated by a straight current source of infinite length are applied to the sea/seabed interface. The field components are calculated numerically and are compared to the field components in seawater of infinite extent. At the seafloor boundary, the fields can propagate longer distances because of the lower seabed conductivities. The new horizontal component of the magnetic field generated as a result of the existence of the sea/seabed interface becomes larger than the vertical component of the magnetic field at large distances; it is also more sensitive to the conductivity of the seabed at low frequencies. The results indicate that there is an optimal frequency at which two of the field components have a maximum field intensity at a certain distance from the source. Some practical applications are discussed

Seabed propagation of ULF/ELF electromagnetic fields from harmonic dipole sources located on the seafloor

The amplitudes of the quasi-static electromagnetic fields generated at points on the seafloor by harmonic dipole sources (vertically directed magnetic dipoles, horizontally directed magnetic dipoles, vertically directed electric dipoles, and horizontally directed electric dipoles) also located on the seafloor are computed using a numerical integration technique. The primary purpose of these computations is to obtain field amplitudes that can be used in undersea communication studies. An important secondary purpose is to examine the enhancements of the fields produced at moderate to large distances by the presence of the relatively less conducting seafloor, as compared with the fields produced at the same distances in a sea of infinite extent, for frequencies in the ULF/ELF bands (frequencies less than 3 kHz). These latter enhancements can be surprisingly large, with increases of 4 orders of magnitude or more being typical at distances of 20 seawater skin depths