Gabapentin--a new antiepileptic agent

Gabapentin is a new antiepileptic drug. Its mechanism of action is not clearly understood, but it seems to differ from that of other antiepileptic drugs. The favourable pharmacokinetic properties of gabapentin make it simple to use. Our preliminary clinical observations with gabapentin at the National Center for Epilepsy are presented. 58 adult patients (mean age 28.9 years), mainly with refractory partial seizures, had gabapentin added to their existing medication. The follow-up period was 6.9 months on average. Only one patient experienced a reduction in seizures of more than 50%, while 25 patients experienced a moderate reduction in seizures (10-50%). The clinical effect was most favourable in patients with secondary generalized tonic-clonic seizures. Gabapentin was well tolerated, and no clinically significant interactions were encountered. Recent observations show that the doses of gabapentin used in our study may have been too low.     

Estimation and reduction of CO2 emissions from crude oil distillation units

Distillation systems are energy-intensive processes, and consequently contribute significantly to the greenhouse gases emissions (e.g. carbon dioxide (CO₂). A simple model for the estimation of CO₂ emissions associated with operation of heat-integrated distillation systems as encountered in refineries is introduced. In conjunction with a shortcut distillation model, this model has been used to optimize the process conditions of an existing crude oil atmospheric tower unit aiming at minimization of CO₂ emissions. Simulation results indicate that the total CO₂ emissions of the existing crude oil unit can be cut down by 22%, just by changing the process conditions accordingly, and that the gain in this respect can be doubled by integrating a gas turbine. In addition, emissions reduction is accompanied by substantial profit increase due to utility saving and/or export.     

Alcohol-induced expression of the CD14 endotoxin receptor protein in rat Kupffer cells

Gut-derived endotoxins (lipopolysaccharide, LPS) are believed to contribute to alcohol-induced liver disease (ALD) by stimulating Kupffer cells, the resident liver macrophages, to release proinflammatory cytokines. This activation is largely mediated by CD14, a high-affinity membrane-anchored receptor for LPS. We observed, by chemiluminescence-enhanced detection, an increase in immunoreactive CD14 protein in Kupffer cells isolated from rats treated with ethanol for 2 weeks. Immunocytofluorescence experiments confirmed that this increase was confined to the membranes of Kupffer cells from the alcohol-treated rats. The increase was regulated pretranslationally: a 3-fold elevation (p < 0.01) in the hepatic level of CD14 mRNA was observed. The marked increase in CD14 expression suggests a new mechanism by which alcohol increases the LPS-mediated cytokine signaling by the liver macrophages, thus promoting the interaction between alcohol and endotoxins in the development of liver damage.     

Co-administration of polyanions with a phosphorothioate oligodeoxynucleotide (CGP 69846A): a role for the scavenger receptor in its in vivo disposition

The effects of co-administering polyanions on the pharmacokinetics of a 20-mer phosphorothioate oligodeoxynucleotide (CGP 69846A), and the role of scavenger receptors in its in vivo disposition, have been investigated. Following i.v. administration, CGP 69846A was rapidly cleared from the plasma and distributed amongst high (e.g. kidney, liver, spleen), low (e.g. skeletal muscle) and negligible (e.g. brain) accumulating tissues. In addition it was shown that: 1) dextran sulphate co-administration has a dose-dependent effect on the disposition of CGP 69846A; 2) CGP 69846A undergoes renal filtration and renal accumulation largely results from tubular reabsorption; 3) cross-inhibition studies are consistent with CGP 69846A being recognized by scavenger receptors in vitro and in vivo; and 4) the scavenger receptor may be an important determinant for the in vivo disposition of CGP 69846A in mice. These studies contribute toward an increased understanding of the mechanism underlying the pharmacokinetic behaviour of phosphorothioate oligodeoxynucleotides.     

Characterization of a mouse monoclonal IgG3 antibody to the tumor-associated globo H structure produced by immunization with a synthetic glycoconjugate

OBJECTIVE: The objective of this study was to assess the degree of BP Tracking from childhood to adulthood and to evaluate whether high BP levels persist over time and progress to adult hypertension. PATIENTS AND METHODS: Two hundred and twenty-two healthy schoolchildren living in the North of Portugal were assessed at 17 year intervals, starting in 1979 (cohort 1) aged 5 to 18 years, and again in 1996 (cohort 2). Tracking indices (Ti) were calculated as follows: Ti = (2x + y-z) /N/0.89, where x, y and z refer to the total number in the same, adjacent and remote trisections, respectively, and N = x + y + z. If Ti > 1 there is positive tracking. RESULTS AND CONCLUSIONS: For systolic and diastolic blood pressure, all Ti were greater than 1.0. All individuals that remained in the 3rd tertil, 17 years later, weigh more and are more obese than those of the 1st tertil. 56.6% of the individuals that belong to the 3rd tertil are now hypertensive, which means that a significant percentage of the children with high blood pressure in the first survey will be hypertensive in the future.