Computer simulation of neuronal toxicity in the spinal cord

Abstract

The use of computers to model biological systems is a relatively new research tool. For examplel it is possible to write mathematical systems to model neuronal activity involved in memory and learning and to model blood flow in any organ such as the brain. There is also an interest in designing computer-controlled machines to simulate human activities such as hand movements and vision. One of the most important uses of computer modeling is as a research tool to test hypotheses and aid in formulating new hypotheses. This enables the investigator to apply preliminary tests on several experimental strategies and select for animal experimentation the ones that are most likely to produce unambiguous and interpretable results. In the following articlel we describe a computer model of neuron toxicity in the mammalian spinal cord. [Neural Res 1997; 19: 340–348]     

Association Notes

Diagnostic procedures for study of the urinary tract are easily adaptable to patients of all age groups, and technical developments have made possible the surgical correction of many anomalies of the genitourinary tract. Early recognition and correction, when possible, are mandatory. Obstructive anomalies are of the greatest immediate importance because of their adverse effect on renal function.     

A new early cognitive screening measure to detect cognitive side-effects of electroconvulsive therapy?

Cognitive side-effects from electroconvulsive therapy (ECT) can be distressing for patients and early detection may have an important role in guiding treatment decisions over the ECT course. This prospective study examined the utility of an early cognitive screening battery for predicting cognitive side-effects which develop later in the ECT course. The screening battery, together with the Mini Mental Status Examination (MMSE), was administered to 123 patients at baseline and after 3 ECT treatments. A more detailed cognitive battery was administered at baseline, after six treatments (post ECT 6) and after the last ECT treatment (post treatment) to assess cognitive side-effects across several domains: global cognition, anterograde memory, executive function, speed and concentration, and retrograde memory. Multivariate analyses examined the predictive utility of change on items from the screening battery for later cognitive changes at post ECT 6 and post treatment. Results showed that changes on a combination of items from the screening battery were predictive of later cognitive changes at post treatment, particularly for anterograde memory (p < 0.01), after controlling for patient and treatment factors. Change on the MMSE predicted cognitive changes at post ECT 6 but not at post treatment. A scoring method for the new screening battery was tested for discriminative ability in a sub-sample of patients. This study provides preliminary evidence that a simple and easy-to-administer measure may potentially be used to help guide clinical treatment decisions to optimise efficacy and cognitive outcomes. Further development of this measure and validation in a more representative ECT clinical population is required.     

Mutual link among the approaches to clipping of basilar aneurysms

Abstract

We report on a series of 48 patients, ages 74 to 20 year, with hypophyseal adenomas. Of these, 46 (96%) had secreting tumors, 3 had Cushing’s disease, 9 had somatotrophinomas, and 34 (29 females and 5 males) had prolactinomas. Thirty cases were diagnosed as intrasellar adenomas (62%) while the remaining eighteen (38%) presented extrasellar expansion. Of 9 acromegalic patients, 7 had typical clinical and biochemical features while 2 were exclusively prognatic with normal basal GH levels, but abnormal dynamic tests. Prolactinomas were npninvasive in women and faster growing and more extensive in men. Forty seven patients underwent surgery. Five of these required craniotomy and the rest were approached through the sphenoidal bone (TSf). Remission was achieved in Cushing’s disease, acromegaly, and female intrasellar prolactinomas. Larger tumors such as nonsecreting adenomas and male prolactinomas showed poor results after undergoing subtotal resections, with persistance of endocrinological disturbances. From our findings it appears that these tumors are not more aggressive in youths than in adults. Because there was a close relationship between tumor size, invasiveness, and the patients, final outcome, we conclude that early diagnosis and treatment is essential. Frequent complaints in adolescents such as irregular menses, retarded puberty, and growth disorders should be thoroughly investigated and not merely considered as transient or ‘functional’ [Neural Res 1998; 20: 415–417]     

Heptanoate as a neural fuel: energetic and neurotransmitter precursors in normal and glucose transporter I-deficient (G1D) brain

It has been postulated that triheptanoin can ameliorate seizures by supplying the tricarboxylic acid cycle with both acetyl-CoA for energy production and propionyl-CoA to replenish cycle intermediates. These potential effects may also be important in other disorders associated with impaired glucose metabolism because glucose supplies, in addition to acetyl-CoA, pyruvate, which fulfills biosynthetic demands via carboxylation. In patients with glucose transporter type I deficiency (G1D), ketogenic diet fat (a source only of acetyl-CoA) reduces seizures, but other symptoms persist, providing the motivation for studying heptanoate metabolism. In this work, metabolism of infused [5,6,7-¹³C₃]heptanoate was examined in the normal mouse brain and in G1D by ¹³C-nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS). In both groups, plasma glucose was enriched in ¹³C, confirming gluconeogenesis from heptanoate. Acetyl-CoA and glutamine levels became significantly higher in the brain of G1D mice relative to normal mice. In addition, brain glutamine concentration and ¹³C enrichment were also greater when compared with glutamate in both animal groups, suggesting that heptanoate and/or C5 ketones are primarily metabolized by glia. These results enlighten the mechanism of heptanoate metabolism in the normal and glucose-deficient brain and encourage further studies to elucidate its potential antiepileptic effects in disorders of energy metabolism.