Praziquantel form, dietary application method and dietary inclusion level affect palatability and efficacy against monogenean parasites in yellowtail kingfish.

The bitterness of racemic praziquantel (PZQ) currently constrains its use as an in-feed treatment against monogenean flukes in finfish aquaculture. In an effort to increase the palatability of diets containing racemic PZQ for yellowtail kingfish, the palatability and efficacy of 2 forms of racemic PZQ (powder or powder within microcapsules) against natural infestations of skin and gill flukes were compared using 2 different dietary application methods (incorporated within the pellet mash prior to extrusion or surface-coated after extrusion) at active dietary inclusion levels of 8, 16 and 25 g kg-1 in large (3.5-4 kg) yellowtail kingfish.

Endovascular coil occlusion of 152 middle cerebral artery aneurysms: initial and midterm angiographic and clinical results.

Object: The object of this study was to evaluate the initial and mid-term angiographic and clinical results after endovascular coil occlusion of middle cerebral artery (MCA) aneurysms at the authors' institution.

Methods: The authors conducted a retrospective analysis of a consecutive series of 152 MCA aneurysms (73 ruptured) treated by endovascular coiling in 140 patients. Angiographic and clinical data at initial and midterm follow-up as well as procedure-related complications were prospectively registered.

Novel CFTR mutations in black cystic fibrosis patients.

Cystic fibrosis (CF) is considered as a rare disease in black Africans. In fact, this disease is likely to be underestimated since clinical features consistent with CF diagnosis are often ascribed to environmental factors such as malnutrition. Very little is known about CFTR mutations in affected patients from Central Africa.

Prenatal diagnosis of carnitine palmitoyltransferase 2 deficiency in chorionic villi: a novel approach.

Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common autosomal recessive inherited disease of the mitochondrial long-chain fatty acid (LCFA) beta-oxidation, may result in three distinct clinical phenotypes, namely, a mild adult muscular form, a severe infantile hepatocardiomuscular disease, and a neonatal form, which includes dysmorphic features in addition to hepatocardiomuscular symptoms. Both the latter forms are life-threatening diseases, and prenatal diagnosis (PND) can be offered to couples at a one-fourth risk of having an affected child. PND of CPT2 deficiency hitherto relied mostly on mutation detection from fresh chorionic villi (10 weeks' gestation), since CPT2 activity could be assayed on cultured amniocytes only (16-17 weeks' gestation).

Functional and structural basis of carnitine palmitoyltransferase 1A deficiency.

Carnitine palmitoyltransferase 1A (CPT1A) is the key regulatory enzyme of hepatic long-chain fatty acid beta-oxidation. Human CPT1A deficiency is characterized by recurrent attacks of hypoketotic hypoglycemia. We presently analyzed at both the functional and structural levels five missense mutations identified in three CPT1A-deficient patients, namely A275T, A414V, Y498C, G709E, and G710E.

Correction of fatty acid oxidation in carnitine palmitoyl transferase 2-deficient cultured skin fibroblasts by bezafibrate.

Carnitine palmitoyltransferase 2 (CPTII) deficiency is among the most common inborn errors of mitochondrial fatty acid beta-oxidation (FAO). Clinical phenotype varies in relation to the metabolic block, as assessed by studies of FAO in patient fibroblasts. Thus, fibroblasts from patients with mild manifestations have appreciable residual CPTII enzyme activity, in contrast to those from severely affected patients.

Correlation between genotype, metabolic data, and clinical presentation in carnitine palmitoyltransferase 2 (CPT2) deficiency.

Carnitine palmitoyltransferase 2 (CPT2) deficiency, the most common inherited disease of the mitochondrial long-chain fatty acid (LCFA) oxidation, may result in distinct clinical phenotypes, namely a mild adult muscular form and a severe hepatocardiomuscular disease with an onset in the neonatal period or in infancy. In order to understand the mechanisms underlying the difference in severity between these phenotypes, we analyzed a cohort of 20 CPT2-deficient patients being affected either with the infantile (seven patients) or the adult onset form of the disease (13 patients). Using a combination of direct sequencing and denaturing gradient gel electrophoresis, 13 CPT2 mutations were identified, including five novel ones, namely: 371G>A (R124Q), 437A>C (N146T), 481C>T (R161W), 983A>G (D328G), and 1823G>C (D608H).

Organization of the human liver carnitine palmitoyltransferase 1 gene ( CPT1A) and identification of novel mutations in hypoketotic hypoglycaemia.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid oxidation. CPT1 controls the import of long-chain fatty acids into the mitochondria, where they are oxidized. Two CPT1 isoforms, the so-called "liver" and "muscle" CPT1s encoded by the CPT1Aand CPT1Bgenes, respectively, have been identified so far.

[MRI and pelvic prolapse].

Static and dynamic pelvic IRM is nowadays part of the diagnostic work up of pelvic prolapse. It is a second line examination, diagnosis being made primarily on the basis of findings at physical pelvic examination. Advantages of MR imaging include lack of ionising radiation, simplicity, multiplanar imaging capability, and possibility to explore at the same time the three compartments and the pelvic floor.

[Spontaneous intracranial hypotension: an unrecognized diagnosis].

We report an observation of spontaneous intracranial hypotension occurring in a 32-year-old man. The diagnosis of intracranial hypotension is easy in a suggestive context: after a lumbar puncture or a diversion of CSF. Clinical and CSF cytological features can mimic chronic meningitis leading to false diagnosis and erroneous therapeutic.

Hepatic carnitine palmitoyl transferase 1 (CPT1 A) deficiency in North American Hutterites (Canadian and American): evidence for a founder effect and results of a pilot study on a DNA-based newborn screening program.

We describe six patients with hepatic carnitine palmitoyl transferase (CPT1 A) deficiency who are members of a large extended Hutterite kindred living in widely scattered communities in the United States and Canadian Prairies. Two patients have significant neurological impairment due to severe recurrent hypoglycemic crises. The remaining four patients with earlier detection and treatment have near normal outcomes.

Molecular and enzymatic characterization of a unique carnitine palmitoyltransferase 1A mutation in the Hutterite community.

Hepatic carnitine palmitoyltransferase 1 (CPT1A) deficiency is a rare disorder of mitochondrial fatty acid oxidation inherited as an autosomal recessive trait. Symptomatology comprises attacks of hypoketotic hypoglycemia with risk of sudden death or neurological sequelae. Only one CPT1A mutation has been reported so far.

Genotype/phenotype correlation in carnitine palmitoyl transferase II deficiency: lessons from a compound heterozygous patient.

Carnitine palmitoyl transferase II deficiency, an inherited disorder of long-chain fatty acid oxidation, may result in either a mild form (muscle disease in adults) or a severe form (hepatocardiomuscular syndrome in infants). The difference in severity between these two forms is related to a difference in levels of residual carnitine palmitoyl transferase II activity and long-chain fatty acid oxidation and in genotypes. Few data are, however, available regarding compound heterozygotes for a 'mild' and a 'severe' carnitine palmitoyl transferase II mutation.

Carnitine palmitoyltransferase deficiencies.

Carnitine palmitoyltransferase (CPT) deficiencies are common disorders of mitochondrial fatty acid oxidation. The CPT system is made up of two separate proteins located in the outer- (CPT1) and inner- (CPT2) mitochondrial membranes. While CPT2 is a ubiquitous protein, two tissue-specific CPT1 isoforms-the so-called "liver" (L) and "muscle" (M) CPT1s-have been shown to exist.

Defects in activation and transport of fatty acids.

The oxidation of long-chain fatty acids in mitochondria plays an important role in energy production, especially in skeletal muscle, heart and liver. Long-chain fatty acids, activated to their CoA esters in the cytosol, are shuttled across the barrier of the inner mitochondrial membrane by the carnitine cycle. This pathway includes four steps, mediated by a plasma membrane carnitine transporter, two carnitine palmitoyltransferases (CPT I and CPT II) and a carnitine-acylcarnitine translocase.

Does the polymorphism 677C-T of the 5,10-methylenetetrahydrofolate reductase gene contribute to homocysteine-related vascular disease?

Whether the 677C-T polymorphism of the methylene tetrahydrofolate reductase (MTHFR) gene acts as a risk factor for homocysteine-related vascular disease remains a matter of debate. Testing for the 677C-T nucleotide substitution and assay of plasma homocysteine were carried out simultaneously in 69 controls and 113 vascular disease patients from the Paris area. The variant gene frequency as well as the variant homozygous genotype frequency were very similar in controls and patients.

Ligation of CD4 surface antigen induces rapid tyrosine phosphorylation of the cytoskeletal protein ezrin.

Ezrin is a cytoskeletal protein which is tyrosine phosphorylated in human T lymphocytes upon stimulation through CD3 antigen (Egerton, M., Burgess, W., Chen, D.

Opposing effects of protein tyrosine kinase inhibitors on the monoclonal antibody induced internalization of CD3 and CD4 antigens.

We have previously demonstrated that the monoclonal antibody (mAb)-induced modulation of CD3 and CD4 antigens from the surface of human peripheral blood lymphocytes is not dependent from protein kinase C activity (Thuillier et al., Eur. J.

The activation of protein kinase C is not necessary for the monoclonal antibody-induced modulation of CD3 and CD4 antigens.

We studied the effect of staurosporine, a potent inhibitor of protein kinase C (PKC) activity, on the phorbol ester- or monoclonal antibody (mAb)-induced modulation of CD3 and CD4 surface antigens. Staurosporine (10(-5) M) completely inhibited phorbol ester-induced modulation but had no effect on that induced by mAb. These results indicate that the down-regulation of CD3 and CD4 observed after activation of the cells by the corresponding mAb is independent from PKC-mediated phosphorylations, and thus that the activation of PKC is sufficient but not necessary to induce the modulation of CD3 and CD4 antigens.

Phenotypic and functional characteristics of human newborns' B lymphocytes.

It has been demonstrated two major facts concerning human newborns' B lymphocytes: 1) they differentiate poorly into Ig-producing cells and 2) they express CD5 and CD1c membrane proteins. We have further analyzed human newborns' B cell characteristics and found that approximately half of them express activation Ag, i.e.

Metabolism of pyrimidine bases and nucleosides by pyrimidine-nucleoside phosphorylases in cultured human lymphoid cells.

The anabolism of pyrimidine ribo- and deoxyribonucleosides from uracil and thymine was investigated in phytohemagglutinin-stimulated human peripheral blood lymphocytes and in a Burkitt's lymphoma-derived cell line (Raji). We studied the ability of these cells to synthesize pyrimidine nucleosides by ribo- and deoxyribosyl transfer between pyrimidine bases or nucleosides and the purine nucleosides inosine and deoxyinosine as donors of ribose 1-phosphate and deoxyribose 1-phosphate, respectively: these reactions involve the activities of purine-nucleoside phosphorylase, and of the two pyrimidine-nucleoside phosphorylases (uridine phosphorylase and thymidine phosphorylase). The ability of the cells to synthesize uridine was estimated from their ability to grow on uridine precursors in the presence of an inhibitor of pyrimidine de novo synthesis (pyrazofurin).

Energy metabolism in adenosine deaminase-inhibited human erythrocytes.

The metabolic changes induced by the deoxycoformycin inhibition of adenosine deaminase were studied in human erythrocytes incubated with nucleosides. 1 Adenosine nucleotide levels and glycolytic rate were increased by adenosine. 2 With deoxyadenosine, the cellular ATP level was reduced when dATP increased and the glycolytic rate was similarly enhanced.

Synergistic toxicity of pyrazofurin and cytidine in cytidine deaminase deficient lymphoid cells (Raji).

The intermediary metabolism of pyrimidine nucleosides was studied in a line of human B lymphoblasts (Raji) in which pyrimidine de novo synthesis deficiency was pharmacologically induced by pyrazofurin. It was found that Raji cells are cytidine deaminase deficient that cytidine has a synergistic effect on the toxicity of pyrazofurin towards these cytidine deaminase deficient cells, affecting both the proliferation and the viability of the cells. Indirect evidences suggest that this synergistic toxicity is not mediated by an effect on nucleoside diphosphate reductase nor on the first steps of pyrimidine de novo synthesis.