Молодь і політика: соціологічні парадокси та українські реалії

The exchange of phosphatidylcholine between intact human or rat erythrocytes and rat liver microsomes was greatly stimulated by phosphatidylcholine-specific exchange proteins from rat liver and beef liver. It was found, however, that compared to the exchange reaction between phospholipid vesicles and rat liver microsomes, much higher concentrations of exchange protein were required in the case of intact red blood cells and microsomes. In human erythrocytes, 75% of the phosphatidylcholine was available for exchange within 2 h at 37°C. No additional exchange was observed during the next 2 h, indicating slow, if any, transbilayer movement of the residual phosphatidylcholine. In rat erythrocytes 50-60% of the phosphatidylcholine was readily available for the exchange proteins. The residual phosphatidylcholine was exchanged at a much lower rate with a half time for equilibration of 7 h. These results confirm in an independent way the asymmetric distribution of phosphatidylcholine over the membrane of human and rat erythrocytes as well as the occurrence of a slow transbilayer movement of this lipid in rat erythrocytes

Quantification of Globotriaosylsphingosine in Plasma and Urine of Fabry Patients by Stable Isotope Ultraperformance Liquid Chromatography-Tandem Mass Spectrometry

Bio-organic Synthesi

Screening for Fabry disease in high-risk populations: a systematic review

INTRODUCTION: Fabry disease (FD) may present with left ventricular hypertrophy, renal insufficiency or stroke. Several studies investigated FD prevalence in populations expressing these symptoms. We conducted a systematic review to calculate the overall prevalence of FD in these cohorts. METHODS: We searched online databases for studies on screening for FD. We recorded study population selection, screening methods and outcome of screening. RESULTS: We identified 20 studies, 10 of which included both male and female patients. In all (N=19) studies with male and almost all (N=10) with female patients aGal A activity was used as screening method. In males on dialysis (10 studies) overall FD prevalence was 0.33% (95% CI 0.20-0.47) and in females (6 studies) 0.10% (95%CI 0-0.19). Combined prevalence of FD in patients with renal transplant was 0.38% in males (95% CI 0.07-0.69) and 0% in females. In patients with LVH, selection of study-population and differences in the method of screening hampered the calculation of an overall prevalence (ranging from 0.9-3.9% in males and 1.1-11.8% in females). In premature strokes (N=2 studies) overall FD prevalence was 4.2% (95CI 2.4-6.0) in males and 2.1% (95CI 0.5-3.7)) in females. DISCUSSION: Prevalence of FD in dialysis patients is 0.33% for males and 0.10% for females. Prevalence of FD in LVH is at least 1% for both genders. In females most studies were performed with aGal A activity measurements as screening tool, although this method fails to detect 1/3 of female patients with FD, underestimating the overall prevalence in female

Screening for Fabry disease in high-risk populations: a systematic review

INTRODUCTION: Fabry disease (FD) may present with left ventricular hypertrophy, renal insufficiency or stroke. Several studies investigated FD prevalence in populations expressing these symptoms. We conducted a systematic review to calculate the overall prevalence of FD in these cohorts. METHODS: We searched online databases for studies on screening for FD. We recorded study population selection, screening methods and outcome of screening. RESULTS: We identified 20 studies, 10 of which included both male and female patients. In all (N=19) studies with male and almost all (N=10) with female patients aGal A activity was used as screening method. In males on dialysis (10 studies) overall FD prevalence was 0.33% (95% CI 0.20-0.47) and in females (6 studies) 0.10% (95%CI 0-0.19). Combined prevalence of FD in patients with renal transplant was 0.38% in males (95% CI 0.07-0.69) and 0% in females. In patients with LVH, selection of study-population and differences in the method of screening hampered the calculation of an overall prevalence (ranging from 0.9-3.9% in males and 1.1-11.8% in females). In premature strokes (N=2 studies) overall FD prevalence was 4.2% (95CI 2.4-6.0) in males and 2.1% (95CI 0.5-3.7)) in females. DISCUSSION: Prevalence of FD in dialysis patients is 0.33% for males and 0.10% for females. Prevalence of FD in LVH is at least 1% for both genders. In females most studies were performed with aGal A activity measurements as screening tool, although this method fails to detect 1/3 of female patients with FD, underestimating the overall prevalence in female

Glycan profiling of urine, amniotic fluid and ascitic fluid from galactosialidosis patients reveals novel oligosaccharides with reducing end hexose and aldohexonic acid residues

Urine, amniotic fluid and ascitic fluid samples of galactosialidosis patients were analyzed and structurally characterized for free oligosaccharides using capillary high-performance anion-exchange chromatography with pulsed amperometric detection and online mass spectrometry. In addition to the expected endo-beta-N-acetylglucosaminidase-cleaved products of complex-type sialylated N-glycans, O-sulfated oligosaccharide moieties were detected. Moreover, novel carbohydrate moieties with reducing-end hexose residues were detected. On the basis of structural features such as a hexose-N-acetylhexosamine-hexose-hexose consensus sequence and di-sialic acid units, these oligosaccharides are thought to represent, at least in part, glycan moieties of glycosphingolipids. In addition, C-1-oxidized, aldohexonic acid-containing versions of most of these oligosaccharides were observed. These observations suggest an alternative catabolism of glycosphingolipids in galactosialidosis patients: oligosaccharide moieties from glycosphingolipids would be released by a hitherto unknown ceramide glycanase activity. The results show the potential and versatility of the analytical approach for structural characterization of oligosaccharides in various body fluids.Proteomic

Phospholipid transfer activities in morris hepatomas and the specific contribution of the phosphatidylcholine exchange protein

Phospholipid transfer activities for phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine were measured in three hepatomas of increasing growth rate and degree of dedifferentiation, the hepatomas 7787, 9633 and 7777, and compared to the activities found in normal and host liver. A 2–3-fold increase was found in the phosphatidylcholine and phosphatidyinositol transfer activities in the fast-growing 7777 hepatoma, while these activities were moderately or not increased in the 7787 and 9633 hepatomas. Phosphatidylethanolamine transfer was found to be extremely low in all three hepatomas. The possible significance of these findings with respect to the altered phospholipid content and composition of the hepatoma membranes is discussed. The contribution of the phosphatidylcholine specific exchange protein to the total phosphatidylcholine transfer activity was determined in normal and host liver and in the hepatomas 7777 and 9633 with the aid of a phosphatidylcholine exchange protein specific antiserum. To this end a new procedure for the purification of the phosphatidylcholine exchange protein from rat liver was developed which leads to a final purification factor of 5300 and a high overall yield of 17%. In addition, this protein was chemically and immunologically characterized and its properties were compared to those of the bovine phosphatidylcholine exchange protein purified in our laboratory previously

Glucocerebrosidase genotype of Gaucher patients in The Netherlands: limitations in prognostic value

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Consequences of a global enzyme shortage of agalsidase beta in adult Dutch Fabry patients

ABSTRACT: BACKGROUND: Enzyme replacement therapy is currently the only approved therapy for Fabry disease. From June 2009 on, viral contamination of Genzyme's production facility resulted in a worldwide shortage of agalsidase beta leading to involuntary dose reductions (approved dose 1 mg/kg/eow, reduced dose 0.5 mg/kg/m), or switch to agalsidase alpha (administered dose 0.2 mg/kg/eow). An assessment report from the European Medicines Agency (EMA) raised serious concerns about an increase in adverse events at lower dosages of agalsidase beta. We determined the influence of the shortage on clinical event incidence and the most sensitive biochemical marker (lysoGb3) in Dutch Fabry patients. METHODS: The incidence of clinical events per person per year was calculated from start of agalsidase beta treatment until the shortage, and was compared to the incidence of clinical events during the shortage period. In addition, plasma lysoGb3, eGFR, quality of life (SF-36) and brief pain inventory (BPI) questionnaires were analysed. RESULTS: All thirty-five Dutch Fabry patients using agalsidase beta (17 males) were included. Mean clinical event incidence was unchanged: 0.15 events per person per year before versus 0.15 during the shortage (p=0.68). In total 28 clinical events occurred in 14 patients during 4.6 treatment years, compared to 7 events in 6 patients during the 1.3 year shortage period. eGFR and BPI scores were not significantly altered. Two SF-36 subscales were significantly but minimally reduced in females. In males, lysoGb3 increased with a median of 8.1 nM (range 2.5-29.2) after 1 year of shortage (p=0.001). Increases in lysoGb3 were found in both patients switching to agalsidase alpha and on a reduced agalsidase beta dose. Antibody status, treatment duration or clinical event incidence showed no clear correlation to lysoGb3 increases. CONCLUSIONS: No increase in clinical event incidence was found in the adult Dutch Fabry cohort during the agalsidase beta shortage. Increases in lysoGb3, however, suggest recurrence of disease activit

Diagnostic dilemmas in Fabry disease: a case series study on GLA mutations of unknown clinical significance

Item does not contain fulltextFabry disease' (FD) phenotype is heterogeneous: alpha-galactosidase A gene mutations (GLA) can lead to classical or non-classical FD, or no FD. The aim of this study is to describe pitfalls in diagnosing non-classical FD and assess the diagnostic value of plasma globotriaosylsphingosine. This is a case series study. Family 1 (p.A143T) presented with hypertrophic cardiomyopathy (HCM), absent classical FD signs, high residual alpha-galactosidase A activity (AGAL-A) and normal plasma globotriaosylsphingosine. Co-segregating sarcomeric mutations were found. Cardiac biopsy excluded FD. In family 2 (p.P60L), FD was suspected after kidney biopsy in a female with chloroquine use. Males had residual AGAL-A, no classical FD signs and minimally increased plasma globotriaosylsphingosine, indicating that p.P60L is most likely non-pathogenic. Non-specific complications and histology can be explained by chloroquine and alternative causes. Males of two unrelated families (p.R112H) show AGAL-A 50 nmol/l). Histological evidence suggests a variable penetrance of this mutation. Patients with GLA mutations and non-specific findings such as HCM may have non-classical FD or no FD. Other (genetic) causes of FD-like findings should be excluded, including medication inducing FD-like storage. Plasma globotriaosylsphingosine may serve as a diagnostic tool, but histology of an affected organ is often mandatory