Conventional spinal radiography as a supplement to the neurologic assessment in myelomeningocele

In patients born with a myelomeningocele early assessment of the severity of the anomaly is mandatory for planning of therapy. Conventional spinal radiography, although a routine examination, in many hospitals has been regarded as less rewarding. However, in this retrospective investigation of 92 patients, a reasonable conformity was found between conventional radiograms and neurologic deficit at follow-up. There was no significant difference between the results of radiologic examinations carried out during the first 1 to 10 weeks after birth and the later neurologic findings. Hence, the simple radiologic assessment has proved a valuable baseline examination in these patients. In cases with discrepancy between the conventional radiologic and the neurologic findings, and in cases with a course diverging from the anticipated, more sophisticated methods of imaging are recommended.     

Brain biopterin metabolism in chronic experimental hepatic encephalopathy

Chronic hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with a substantial increase in the brain L-tryptophan (L-TRP) level. Moreover, a supranormal L-TRP hydroxylating activity in the brain suggests an induced enzymatic process in chronic HE. GTP-cyclohydrolase I (GTPCHI) and tetrahydrobiopterin (BH4) are two major factors besides L-TRP that are involved in regulating the brain L-TRP hydroxylating activity. We therefore determined the GTPCHI activity, the total biopterin and the BH4 concentrations in the neocortex and mesencephalon-pons of portacaval shunted (PCS) rats. The encephalopathic component in PCS rats was accounted for by studying open field behaviour. The acute effects of a single parenteral L-TRP challenge were also evaluated. The basal GTPCHI activities in PCS rats were decreased bu 50% (p<0.05) compared to controls in both investigated brain regions. No significant alterations in brain total biopterin or BH4 levels were present. The PCS rats exhibited a clearly reduced spontaneous locomotor activity. After the exogenous L-TRP load only a lower GTPCHI activity in the neocortex of PCS rats was recorded. We conclude that a perturbation in the brain biopterin metabolism is concomitantly present with behavioural abnormalities in the chronic PCS condition and that the acute effects of a superimposed L-TRP load do not aggravate these disturbances.     

Enzymes of the mevalonate pathway in rat liver nodules induced by 2-acetylaminofluorene treatment

Certain enzymes of the mevalonate pathway have been investigatedin persistent liver nodules induced in the rat by 2-acetylaminofluorene.In these nodules the dolichol level was increased 5-fold, theubiquinone-9 content elevated 6-fold and the amount of cholesterolunchanged. Microsomal ß-hydroxy-ß-methylglutaryl-coenzymeA reductase activity was greatly increased compared to controlliver tissue, which was also the case for the cytosolic farnesylpyrophosphate synthase. A significant elevation of all-trans-geranylgeranylpyrophosphate synthase activity in the cytosol was also observed.The branch-point enzyme of microsomal dolichol synthesis, i.e.cis-prenyltransferase, was decreased in the nodules; whereasthe activity of squalene synthase, the terminal regulating enzymeof cholesterol synthesis, remained unchanged. The dolichol speciesin nodular tissue were redistributed towards the longer chainlength species. One factor regulating the chain length of thepolyisoprene products formed in vitro was shown to be the ratioof the concentrations of isopentenyl pyrophosphate: farnesylpyrophosphate employed. Other regulatory factors in the terminalsteps of this biosynthetic pathway appear to determine the amountsand nature of the final isoprenoid compounds formed in vivo.In contrast to the microsomal trans-prenyltransferase activity,which was unchanged, the activity of nonaprenyl-4-hydroxybenzoatetransferase, an enzyme participating in ubiquinone synthesis,was greatly elevated. The alterations observed in the activitiesof enzymes in the mevalonate pathway can at least partiallyexplain the increased levels of dolichol and ubiquinone andthe unchanged level of cholesterol found in liver nodules. Itis reasonable to propose that this modified mevalonate metabolismwill render nodular cells resistant to certain toxic factorsand prone to cell proliferation.