Chronic progressive myelopathy: its relation to the spinal progressive form of multiple sclerosis

The causes and clinical features of chronic progressive myelopathy (CPM) were evaluated in a retrospective study of 107 patients. A special emphasis was put on those in whom no underlying cause for the myelopathy could be determined. Of 76 such, 39 (51%) had oligoclonal immunoglobulins (Ig) in the CSF and were therefore considered as possible MS, while the remainder, without oligoclonal Ig, were designated "myelopathy of unknown origin" (MUO). Our "possible MS" group was similar clinically to reported series of proven spinal MS, and it seems therefore, that the presence of oligoclonal Ig permits the recognition of a group of patients with myelopathy who might be at a greater risk for MS. Patients with MUO differed from possible MS patients in several clinical characteristics, but most significantly in disease course and levels of functional disability which were more benign in the former. Myelopathy in possible MS patients was also of a primary pyramidal and asymmetrical nature. It is therefore suggested that the segregation of patients with CPM of undetermined origin into 2 separate groups based on the presence or absence of oligoclonal Ig might be of prognostic significance.     

Iodomethylated fatty acid metabolism in mice and dogs

The myocardial uptake of fatty acids labeled with radioactive iodine and injected i.v. can only be evaluated with SPECT if their oxidation kinetics is slow enough. For this reason, we evaluated different iodomethylated fatty acids in mice and dogs to determine which of them shows the highest myocardial uptake and the slowest oxidation. The most suitable was found to be 16-iodo-3-methyl hexadecanoic acid (mono ) since its myocardial fixation was the same as that of the reference, i.e. 16-iodo-9-hexadecenoic acid (IHA), whereas it was degraded more slowly. Thirty min after injection of mono into dogs, the decrease in myocardial activity with respect to the maximum was two fold less than after IHA injection. The myocardial uptake of the two dimethylated fatty acids studied, i.e. 16-iodo-2,2-methyl hexadecanoic acid and 16-iodo-3,3-methyl hexadecanoic acid, was less than that of IHA in mice and dogs. In the latter, the myocardial uptake was so small that we were unable to study the time course of its activity. Consequently, these dimethylated fatty acids are not suitable for the study of the myocardial uptake of fatty acids in man.     

Metabolism of methyl-branched iodo palmitic acids in cultured hepatocytes

The metabolic fate of methyl-branched iodo fatty acids was studied in primary culture of rat hepatocytes. We compared 16-iodo-2-R,S-methyl palmitic acid (2-Me), which can be oxidized, with 16-iodo-3-R,S-methyl palmitic acid (3-Me) which can be oxidized only after an initial oxydation and with 16-iodo-2,2-dimethyl palmitic acid (2,2-Me₂) and 16-iodo-3,3-dimethyl palmitic acid (3,3-Me₂) which cannot be oxidized at all. The normal fate of natural fatty acids was given by comparative experiments with [1-¹⁴C] palmitic acid. Monomethyl-branched iodo fatty acids were taken up in the same range as palmitic acid but more than dimethyl-branched iodo fatty acids. After a 15-h incubation, acido-soluble products (ASP) accounted for 75% of the radioactivity taken up as 16-iodo-2-methyl palmitic acid, 50% as other methyl-branched iodo fatty acids and only 30% as palmitic acid, which indicated that all the methyl-branched iodo fatty acids underwent a strong deiodination process. Fatty acids were esterified in the following order: palmitic acid >16-iodo-3-R,S-methyl palmitic acid>16-iodo-2-R,S-methyl palmitic acid>16-iodo-2,2-dimethyl palmitic acid>16-iodo-3,3-dimethyl palmitic acid. Cultured hepatocytes, labelled for 3 h with the various fatty acids and reincubated for 12 h without fatty acid, secreted large amounts of free dimethylbranched iodo fatty acids as compared to the monomethyl ones and palmitic acid. Only hepatocytes prelabelled with 16-[¹²⁵I]iodo-2,2-dimethyl palmitic acid exhibited an appreciable secretion of labeled triglycerides, but at a lower rate than with [1-¹⁴C] palmitic acid. Conversely, the 16-iodo-monomethyl palmitic acids remained chiefly in hepatocyte triglycerides. Minute amounts of 16-iodo-methyl-branched-palmitic acids were found in hepatocyte or secred phospholipids as compared with palmitic acid. This metabolic fate of methyl-branched iodo palmitic acids argues against their utilization as imaging probes to monitor in vivo the synthesis and the secretion of triglycerides by the liver.     

The effect of hyperoxia on the lungs of rats deficient in essential fatty acids

Morphological alterations in the lungs of rats deficient in either or both of vitamin E and essential fatty acids were investigated after exposure to hyperoxia for 48h. In rats deficient in both vitamin E and essential fatty acids, there was damage to type-2 alveolar cells observed as swollen mitochondria and bleb formation in the cytoplasm. None of these changes was found in rats deficient in only one of these substances. Hyperoxia in rats deficient in both substance also caused destruction of the capillary endothelial cells and edema in the interstitium. The lungs of rats deficient in only one of the substances showed some edema in the capillary endothelial cells, but not destruction, and less interstitial edema. These findings suggest that simultaneous deficiency in vitamin E and essential fatty acids facilitates lung damage in rats exposed to hyperoxia.(Murakami R, Obara H, Momota T et al.: The effect of hyperoxia on the lungs of rats deficient in essential fatty acids. J Anesth 3: 149–154, 1989)     

Monocyte cytokine secretion induced by chemically-defined derivatives of Klebsiella pneumoniae.

The capacity of a K. pneumoniae membrane proteoglycan (Kp-MPG) and four of its chemically defined derivatives to activate human monocytes was studied by measuring immunoreactive IL-1 beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha) in culture supernatants. Monocyte culture supernatants were also tested for their comitogenic activity on concanavalin A-stimulated thymocytes and for their cytotoxic activity on the mouse fibroblastic L929 cell line. The four Kp-MPG derivatives were: (i) an acylpoly(1-3)galactoside (APG); (ii) an APG preparation submitted to acid hydrolysis which removed all fatty acids but left intact the galactose chain of APG (GC-APG); (iii) a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and (iv) a polymer of the latter compound (APG pol). Kp-MPG induced the synthesis of IL-1 beta, IL-6 and TNF-alpha with dose-responses and kinetics similar to those of Salmonella minnesota lipopolysaccharide (Sm-Re-LPS). APG pol and EFA-APG induced the secretion of the three cytokines with lower potency than Kp-MPG or Sm-Re-LPS. APG did not trigger any detectable cytokine production and GC-APG induced only borderline and inconsistent responses. Our data demonstrate the critical role of ester-linked C14 and C16 fatty acids in the triggering of monocyte response to Kp-MPG derivatives.     

Distal Proctocolitis and n-3 Polyunsaturated Fatty Acids (n-3 PUFAs): The Mucosal Effect In Situ

It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.     

Effects of a diet rich in Q-3 fatty acids on left ventricular geometry and dynamics in spontaneously hypertensive rats

Summary The aim of the present study was to investigate the chronic effects of a dietetic antihypertensive treatment on blood pressure, ventricular dynamics and geometry of the pressure loaded heart. Spontaneously hypertensive rats (SHR) received a standard diet enriched with 10% mackerel oil, containing 30% polyunsaturated Q-3 fatty acids, over a period of 70 days. As described previously the diet reduced blood pressure permanently by 40-50 mm Hg. Despite this reduction, the degree of left ventricular hypertrophy was only slightly (statistically insignificantly) reduced. This was probably a result of an increase in sympathetic tone as indicated by a raised pulse rate. On the other hand, the treatment prevented the development of eccentric hypertrophy, typical to the SHR, without changing the elastic material properties of the myocardium. Since the age-matched controls did not show significant degenerative alterations, protective effects at the level of myocardial tissue could not be demonstrated. Furthermore, future investigations need to investigate why myocardial contractility of the treated animals diminishes as observed in this study.     

Are thrombocyte membranes altered in Alzheimer''s disease? A morphometric and biochemical study

Morphometric analysis of thrombocytes from patients with Alzheimer's disease, from patients with multi-infarct dementia, and from young and agematched healthy control donors, did not reveal any Alzheimer-related increase in internal membranes. Biochemical analysis showed a reduced cholesterol content of thrombocyte membrane preparations from Alzheimer patients relative to age-matched controls, but not relative to multi-infarct dementia patients. Overall distribution of protein kinase C activity (PKC) between cytosol and membrane, in resting as well as in activated thrombocytes from Alzheimer patients, was similar to that in the control groups. However, both Alzheimer and multi-infarct dementia patients had lower cytosolic levels of basal kinase and PKC activities than age-matched controls, while only Alzheimer patients had lower cytoskeletal PKC activity than controls.     

Comparative analysis of seizures induced by intracerebroventricular administration of NMDA,kainate and quisqualate in mice

Summary The dose-related time course and occurrence of different seizure subtypes was examined in mice after i.c.v. administration of N-methyl-D-aspartate (NMDA), kainate (KA) or quisqualate (QA). At doses of 0.2 to 1 nmol, NMDA dose-dependently induced a single clonic-tonic seizure. Low doses (0.1 to 0.3 nmol) of KA induced only mild myoclonus and whole body clonus, which were dose-dependently replaced by short-delay clonic-tonic seizures at higher doses (0.4 to 1.2 nmol). In contrast, mice treated with 13 to 32 nmol of QA exhibited either mild myoclonus or whole body clonus as well as clonic-tonic seizures. Clonic-tonic seizures induced by NMDA or KA appeared at shorter latencies than those induced by QA, whereas whole body clonus induced by KA or QA appeared with long onset latencies. These results clearly show that i.c.v. administration of NMDA, KA and QA produces different patterns of seizures in mice. This study confirms that NMDA, KA and QA induce convulsions through different underlying mechanisms and suggests that different anatomical pathways are involved in these models.