The deamination of dopamine by human brain monoamine oxidase

The deamination of dopamine has been studied in seven regions of human brain. Both A and B forms of the enzyme were found to be active towards this substrate. The ratio of activities of MAO-A: MAO-B was found to vary considerably from brain region to brain region, from about 1:1 for the cerebral and cerebellar cortex to about 1:2 for the pons and medulla oblongata. Enzyme titration studies and comparisons of the substrate specificities of MAO-A and MAO-B across the brain indicated that dopamine was metabolised by the same MAO active centres as other monoamines. In the cerebral cortex, the Km values of MAO-A and -B towards dopamine were found to be 210 and 230 microM, respectively, indicating that the relative contributions of these two forms towards the oxidation of this substrate will not be significantly affected by changes in its concentration.     

Parenteral Use of Diazepam in an Emulsion Formulation. A Clinical Study

A recently described injection formulation for diazepam, consisting of an oil emulsion where the drug is dissolved in the oil phase, has been found to give a lessened degree of side reactions than commercially available preparations. This emulsion formulation was compared to Valium® inj. as premedication in patients undergoing operation for hernia or varices under epidural anaesthesia.
The effects, measured as the degree of drowsiness according to an arbitrary scale, were found to be equal for the two formulations. Neither was there any difference in blood concentrations in the two application groups, respectively, between the preparations used. The propylene glycol content of Valium inj. is said to cause a delayed release of the drug from the injection site after i.m. application, and this is briefly discussed, as well as the possibility of administering the diazepam emulsion continuously, diluted with Intralipid, without the risk of precipitation.     

Self-stimulation and local injections of 6-hydroxydopamine into the rat brain: Enhanced behavioral depressive effects of α-methylparatyrosine

The effects of intracerebral injections of 6-OHDA on self-stimulation were examined. Small amounts of 6-OHDA were injected either in the area ventralis tegmenti (AVT) or laterally in the pedonculus cerebellaris superior (PCS), then all rats were implanted in the AVT. In spite of marked depletion of brain catecholamines, self-stimulation learning was not altered by PCS 6-OHDA injections, whereas, AVT 6-OHDA injections produced a small perturbance. The administration of low doses of AMPT which had no observable effect in control rats, produced a severe depression of self-stimulation rates in 6-OHDA pretreated rats. The depressive effect of AMPT is always more important in rats injected with 6-OHDA in the AVT than those injected at the level of PCS. The respective role of noradrenergic and dopaminergic neurons in AVT self-stimulation are discussed.     

Benign intracranial hypertension and disorders of CSF absorption

Sixteen patients suffering from benign intracranial hypertension were studied by a continuous measurement of intraventricular pressure, a simultaneous recording of intraventricular and sagittal sinus pressures, and a measurement of the cerebrospinal fluid (CSF) resistance to drainage. Isotope cisternography was performed and the patency of the dural sinuses verified by direct sinography or phlebography or both. The same procedure was used to study 6 other patients suffering from disorders leading to the same type of intracranial hypertension. In 16, our results confirm a defect in CSF absorption mechanisms linked to an abolition of the pressure gradient between CSF and sagittal sinus in 6 patients, as well as an important increase in CSF resistance to drainage in 10 others. Despite this defect, the CSF circulation was normal in most patients (10 of 12) as demonstrated by isotope cisternography.     

Electrical,contractile, and radiographic studies of the stomach after proximal gastric vagotomy

The effects of proximal gastric vagotomy on the gastric electrical and contractile activities and on gastric emptying of solid food were studied in dogs. Proximal gastric vagotomy produced only minimal alteration of the electrical activity and did not significantly alter the response of the electrical and contractile activities to vagal stimulation (insulin) and local stimulation (food). Barium meal studies showed no delay in gastric emptying time after proximal gastric vagotomy but significant delay after truncal vagotomy. The findings support the clinical impression that gastric motility and empyting (solid) remain relatively normal after proximal gastric vagotomy.     

Glycation, glycoxidation and diabetes mellitus

Advanced glycation end-products (AGEs) result from a reaction between carbohydrates and the free amino groups of proteins, lipids, and DNA. Non enzymatic glycation, glycoxidation with glucose auto-oxidation and the polyol pathway are involved in glycated protein formation. AGEs also named glycotoxins are found in excess in pathological situations such as diabetes mellitus, renal failure, and aging or after absorption of food containing glycated products. Three major pathophysiological mechanisms are described to explain AGE toxicity, first AGEs can accumulate in the vessel wall and in collagen of different tissues; second in situ glycation is possible; third, AGEs bind to cell receptors inducing deleterious consequences. AGE receptor RAGE is a multiligand member of the immunoglobulin superfamily of cell surface molecules. AGE-receptor interaction can alter, macrophage, endothelial cell, mesangial and mesothelial cell functions and can induce inflammation. Oxidant stress, vascular hyperpermeability, vascular cell adhesion molecule-1 (VCAM-1) overexpression and monocytes chemotactic Protein-1 (MCP-1) production have been observed after cell activation by AGEs. AGEs appear to be involved in the genesis of diabetic macro but also microangiopathy such as retinopathy and glomerulosclerosis. New drugs are tested to prevent or break the AGE-protein cross-linkage, or to control the AGE-receptor interaction and their consequences. Dietary treatment, strict glycemic control and preservation of renal function remain the best approach for preventing AGE formation and limiting their deleterious effects.     

Intradialytic parenteral nutrition: comparison of olive oil versus soybean oil-based lipid emulsions

Lipid, oxidative and inflammatory parameters are frequently altered in dialysis patients and may be worsened by intravenous lipid emulsions (ILE). We assessed the efficacy and tolerance of olive as compared with standard soybean oil-based ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing amino acids, glucose, and either olive oil (OO group, n 17) or soybean oil-based ILE (SO group, n 18) were administered in a 5-week randomized, double-blind study. On days 0 and 35, patients' nutritional status was assessed by BMI, normalized protein catabolic rate, predialytic creatinine, serum albumin and transthyretin; lipid metabolism by plasma LDL- and HDL-cholesterol, triacylglycerols, phospholipids, apo A-I, A-II, B, C-II, C-III, E and lipoprotein (a); oxidative status by alpha-tocopherol, retinol, selenium, glutathione peroxidase, malondialdehyde and advanced oxidized protein products; inflammatory status by serum C-reactive protein, orosomucoid, IL-2 and IL-6. No serious adverse event was observed. Significant changes were observed from day 0 to day 35 (P<0.05): nutritional criteria improved (albumin in OO; albumin, transthyretin and creatinine in SO); LDL-cholesterol, apo B, C-II, C-III and apo A-I/A-II ratio increased in both groups. HDL-cholesterol decreased in OO; apo E increased and lipoprotein (a) decreased in SO; alpha-tocopherol/cholesterol ratio increased in OO; malondialdehyde decreased in both groups; IL-2 increased in both groups. The between-group comparison only showed the following differences: alpha-tocopherol/cholesterol increased in OO; lipoprotein (a) decreased in SO. From these data, it was concluded that OO- and SO-based IDPNs similarly improved nutritional status and influenced plasma lipid, oxidative, inflammatory and immune parameters.