Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine

none11noMucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.Coppa, G.V; Gabrielli, O.; Zampini, L.; Maccari, F.; Mantovani, V.; Galeazzi, T.; Santoro, L.; Padella, L.; Marchesiello, R.L.; Galeotti, F.; Volpi, N.Coppa, Giovanni Valentino; Gabrielli, Orazio; Zampini, Lucia; Maccari, F.; Mantovani, V.; Galeazzi, Tiziana; Santoro, Lucia; Padella, Lucia; Marchesiello, R. L.; Galeotti, F.; Volpi, N

Early diagnosis of mucopolysaccharidoses in developing countries: A low cost and easy execution approach

none16noopenGabrielli, Orazio; Zampini, Lucia; Monachesi, Chiara; Marchesiello, Rita Lucia; Padella, Lucia; Santoro, Lucia; Volpi, Nicola; Concolino, Daniela; Fiumara, Agata; Rigon, Laura; Mazzoli, Milena; Carnielli, Virgilio Paolo; Giovagnoni, Andrea; Catassi, Carlo; Galeazzi, Tiziana; Coppa, Giovanni ValentinoGabrielli, Orazio; Zampini, Lucia; Monachesi, Chiara; Marchesiello, Rita Lucia; Padella, Lucia; Santoro, Lucia; Volpi, Nicola; Concolino, Daniela; Fiumara, Agata; Rigon, Laura; Mazzoli, Milena; Carnielli, Virgilio Paolo; Giovagnoni, Andrea; Catassi, Carlo; Galeazzi, Tiziana; Coppa, Giovanni Valentin

Long-term sediment decline causes ongoing shrinkage of the Mekong megadelta, Vietnam

Since the 1990s the Mekong River delta has suffered a large decline in sediment supply causing coastal erosion, following catchment disturbance through hydropower dam construction and sand extraction. However, our new geological reconstruction of 2500-years of delta shoreline changes show that serious coastal erosion actually started much earlier. Data shows the sandy coast bounding river mouths accreted consistently at a rate of +2 to +4 km2/year. In contrast, we identified a variable accretion rate of the muddy deltaic protrusion at Camau; it was < +1 km2/year before 1400 years ago but increased drastically around 600 years ago, forming the entire Camau Peninsula. This high level of mud supply had sharply declined by the early 20th century after a vast canal network was built on the delta. Since then the Peninsula has been eroding, promoted by the conjunction of mud sequestration in the delta plain driven by expansion of rice cultivation, and hysteresis of long-term muddy sedimentation that left the protrusion exposed to wave erosion. Natural mitigation would require substantial increases in sediment supply well above the pre-1990s levels

Variazioni del dermatan solfato plasmatico durante la terapia enzimatica sostitutiva con iduronato-2-solfatasi in un paziente affetto da mucopolisaccaridosi II

Variazioni del dermatan solfato plasmatico durante la terapia enzimatica sostitutiva con iduronato-2-solfatasi in un paziente affetto da mucopolisaccaridosi I

False positive screen test for mucopolysaccharidoses in healthy female newborns

BACKGROUND: In total, 930 urine samples obtained on 2nd and 3rd day from birth have been analyzed for the early diagnosis of Mucopolysaccharidoses. METHODS: Dimethylmethylene blue (DMB) assay and one-dimensional electrophoresis were performed in all urine samples. Agarose gel electrophoresis, before and after treatment with chondroitinase ABC and heparinases, was used for a comprehensive characterization. RESULTS: Out of 930 urine samples 7 showed anomalous electrophoretic pattern; 5 of them had high GAG levels by DMB test. Atypical samples (n\u202f=\u202f7) were analyzed by agarose gel electrophoresis. After enzymatic digestion, some slow bands were still visible. A second urine sample of the above 7 newborns was analyzed at the age of 1\u202fmonth, demonstrating both a normal pattern and normal GAG levels. Additional urine and vaginal mucus samples from 10 term neonates with vaginal bleeding showed the same electrophoretic pattern observed in the 7 false positive samples. CONCLUSIONS: The altered electrophoretic pattern may be due to the presence of glycoproteins and not to specific GAGs, due to high levels of maternal hormones exposure during pregnancy. To our knowledge, this is the first time maternal estrogen hormones are proposed as a likely cause of false-positive urinary glycosaminoglycan screen test in healthy newborns

Baroclinic Tidal Flows and Inundation Processes in Cook Inlet, Alaska: Numerical Modeling and Satellite Observations

A wetting and drying (WAD) algorithm is implemented in a baroclinic three-dimensional ocean circulation model of Cook Inlet, Alaska, where large tidal ranges (≈10 m) regularly expose extensive mudflats. The model includes tides and wind- and buoyancy-induced flows. In the upper Inlet, the model successfully simulates large amplification of tides and propagation of fast (3 ∼ 4 m s−1) tidal bores over shallow mudflats. The simulated return flows during ebb expose large areas (∼100 km2) of the mudflats. Medium-resolution (250- and 500-m) images obtained from the moderate resolution imaging spectroradiometer (MODIS) instruments aboard the Terra and Aqua satellites were used to verify the model results by identifying the location, extent, and temporal changes of the exposed mudflat regions. The results demonstrate the value of operational, medium-resolution remote sensing data in evaluating the WAD model. Sensitivity tests show that WAD produces approximately 20% larger tidal amplitude and 10% slower phase than the corresponding experiment without WAD. In the deep channel of the central Inlet, the confluence of saline water of the lower Inlet with brackish water from rivers and melting ice from land around the upper Inlet produces a salinity front. At the simulated front, strong vertical circulation cells and surface convergence and currents develop, especially during the flood. The characteristics resemble those of “rip tides” often observed in this region