Anabolic effect of human parathyroid hormone fragment on trabecular bone in involutional osteoporosis: a multicentre trial.

After baseline studies, 21 patients with osteoporosis were treated with human parathyroid hormone fragment (PTH 1-34) given as once-daily subcutaneous injections for 6-24 months. The dose used did not cause hypercalcaemia even in the first few hours after injection. Calcium and phosphate balances improved in some patients, but there was no significant improvement in the group values. There were, however, substantial increases in iliac trabecular bone volume: the mean increase, confirmed by repeat blind measurements, was 70% above mean baseline volume. The new bone was histologically normal. Those patients who had the largest increases in 47Ca-kinetic and histomorphometric indices of new bone formation showed the greatest increases in trabecular bone volume, suggesting that treatment with human parathyroid hormone fragment caused a dissociation between formation and resorption rates that was confined to trabecular bone. Since vertebrae are four-fifths composed of trabecular bone, this hormone fragment may prove useful in treating patients with the crush fracture syndrome.     

Model of dissolution in the framework of tissue engineering and drug delivery

Dissolution phenomena are ubiquitously present in biomaterials in many different fields. Despite the advantages of simulation-based design of biomaterials in medical applications, additional efforts are needed to derive reliable models which describe the process of dissolution. A phenomenologically based model, available for simulation of dissolution in biomaterials, is introduced in this paper. The model turns into a set of reaction–diffusion equations implemented in a finite element numerical framework. First, a parametric analysis is conducted in order to explore the role of model parameters on the overall dissolution process. Then, the model is calibrated and validated versus a straightforward but rigorous experimental setup. Results show that the mathematical model macroscopically reproduces the main physicochemical phenomena that take place in the tests, corroborating its usefulness for design of biomaterials in the tissue engineering and drug delivery research areas.     

Evidence that muscarinic potentiation of insulin release is initiated by an early transient calcium entry

The increased insulin release induced by carbamoylcholine (CbCh) in pancreatic islets requires the presence of extracellular Ca2+. Intracellular recordings demonstrate that CbCh produces a transient increase in Ca2+ channel activity lasting from 30 to 60 s. Thereafter activity decreased to levels lower than in controls. When extracellular Ca2+ was present during this initial period, the stimulatory effects of CbCh were not different from those in which Ca2+ was present throughout. These experiments suggest that during muscarinic potentiation of insulin release extracellular calcium is only needed in the first minute.     

Evaluation of the phenylalanine tolerance test in detection of heterozygote carriers of phenylketonuria gene]

The study aimed at identifying heterozygotic phenylketonuria gene carriers with phenylalanine tolerance test performed in Lublin region. Serum phenylalanine concentration has been assayed during fasting and 1 and 2 hours following oral phenylalanine load in the dose of 0.1 g per 1 kg body weight. The study involved 203 individuals of the general population and 29 heterozygotes with phenylketonuria gene. Blood serum phenylalanine was assayed with Guthrie' technique. Statistical analysis has shown that hyperphenylalaninemia is relatively frequent in fasting individuals of the general population (59.1%). The same was demonstrated in 5 heterozygotes. Phenylalanine tolerance test did not allow to identify heterozygotic carries of phenylketonuria gene in the general population though fasting and after phenylalanine load increased blood serum levels of this amino acid are a criterium of hyperphenylalaninemia in the group of tested individuals (29%).     

Thick brachiopod shell concentrations from prodelta and siliciclastic ramp in a Tortonian Atlantic–Mediterranean strait (Miocene, Guadix Basin, southern Spain)

Carbonate production by brachiopods in shallow-water habitats is generally expected to be not sufficiently high and temporally persistent to allow them to form very thick and densely packed shell concentrations. The formation of thick brachiopod concentrations requires long-term persistence of populations with high density of individuals, and such circumstances are assumed to be rare especially during the Cenozoic. However, here we show that the large-sized brachiopod Terebratula terebratula, the most common species in benthic assemblages with epifaunal bivalves and irregular echinoids, formed several decameter- to meter-thick, densely packed concentrations in shallow siliciclastic, high-energy environments, in a seaway connecting the Atlantic Ocean with the Mediterranean Sea during the Latest Tortonian (Late Miocene, Guadix Basin, southern Spain). This brachiopod formed (1) meter-scale, thick, parautochthonous concentrations in a prodelta setting and (2) thin, mainly allochthonous, tide- and storm-reworked concentrations in megaripples and dunes. The abundance of brachiopods at the spatial scale of the Guadix Basin seems to be mainly related to intermediate levels of sedimentation rate and current velocity because abundance and thickness of shell concentrations decline both (1) in onshore direction towards delta foresets with high sedimentation rate generated by debris flows and (2) in offshore direction with increasing levels of tide- and storm-induced substrate instability. Although brachiopods in dune and megaripple deposits are more fragmented, disarticulated, and sorted, and have a higher pedicle/brachial valve ratio than in prodelta deposits, taphonomic damage is still relatively high in prodelta deposits. Terebratula terebratula thus formed thick concentrations in spite of that disintegration processes were relatively intense along the whole depositional gradient. Therefore, population dynamic of this species was probably characterized by production maxima that were comparable to some Cenozoic molluscs in terms of their productivity potential to form thick shell concentrations in shallow subtidal environments. We suggest that temporal changes in brachiopod carbonate production have a significant spatial and phylogenetic component because multiple large-sized species of the family Terebratulidae, which underwent radiation during the Cenozoic, attained high abundances and formed shell concentrations in temperate regions.     

α-<Emphasis Type="SmallCaps">l</Emphasis>-Rhamnosidase of <Emphasis Type="Italic">Aspergillus terreus</Emphasis> immobilized on ferromagnetic supports

α-l-Rhamnosidase from Aspergillus terreus was covalently immobilized on the following ferromagnetic supports: polyethylene terephthalate (Dacron-hydrazide), polysiloxane/polyvinyl alcohol (POS/PVA), and chitosan. The powdered supports were magnetized by thermal coprecipitation method using ferric and ferrous chlorides, and the immobilization was carried out via glutaraldehyde. The activity of the Dacron-hydrazide (0.53 nkat/μg of protein) and POS/PVA (0.59 nkat/μg of protein) immobilized enzyme was significantly higher than that found for the chitosan derivative (0.06 nkat/μg of protein). The activity–pH and activity–temperature profiles for all immobilized enzymes did not show difference compared to the free enzyme, except the chitosan derivative that presented higher maximum temperature at 65 °C. The Dacron-hydrazide derivative thermal stability showed a similar behavior of the free enzyme in the temperature range of 40–70 °C. The POS/PVA and chitosan derivatives were stable up to 60 °C, but were completely inactivated at 70 °C. The activity of the preparations did not appreciably decrease after ten successive reuses. Apparent K _m of α-l-rhamnosidase immobilized on magnetized Dacron-hydrazide (1.05 ± 0.22 mM), POS/PVA (0.57 ± 0.09 mM), and chitosan (1.78 ± 0.24 mM) were higher than that estimated for the soluble enzyme (0.30 ± 0.03 mM). The Dacron-hydrazide enzyme derivative showed better performance than the free enzyme to hydrolyze 0.3% narigin (91% and 73% after 1 h, respectively) and synthesize rhamnosides (0.116 and 0.014 mg narirutin after 1 h, respectively).     

Toxic effects of amyloid fibrils on cell membranes: the importance of ganglioside GM1

The interaction of amyloid aggregates with the cell plasma membrane is currently considered among the basic mechanisms of neuronal dysfunction in amyloid neurodegeneration. We used amyloid oligomers and fibrils grown from the yeast prion Sup35p, responsible for the specific prion trait [PSI(+)], to investigate how membrane lipids modulate fibril interaction with the membranes of cultured H-END cells and cytotoxicity. Sup35p shares no homology with endogenous mammalian polypeptide chains. Thus, the generic toxicity of amyloids and the molecular events underlying cell degeneration can be investigated without interference with analogous polypeptides encoded by the cell genome. Sup35 fibrils bound to the cell membrane without increasing its permeability to Ca(2+). Fibril binding resulted in structural reorganization and aggregation of membrane rafts, with GM1 clustering and alteration of its mobility. Sup35 fibril binding was affected by GM1 or its sialic acid moiety, but not by cholesterol membrane content, with complete inhibition after treatment with fumonisin B1 or neuraminidase. Finally, cell impairment resulted from caspase-8 activation after Fas receptor translocation on fibril binding to the plasma membrane. Our observations suggest that amyloid fibrils induce abnormal accumulation and overstabilization of raft domains in the cell membrane and provide a reasonable, although not unique, mechanistic and molecular explanation for fibril toxicity.     

Growth patterns in relation to drought-induced mortality at two Scots pine (Pinus sylvestris L.) sites in NE Iberian Peninsula

Drought-related tree mortality has become a widespread phenomenon. Scots pine (Pinus sylvestris L.) is a boreal species with high ecological amplitude that reaches its southwestern limit in the Iberian Peninsula. Thus, Iberian Scots pine populations are particularly good models to study the effects of the increase in aridity predicted by climate change models. A total of 78 living and 39 dead Scots pines trees were sampled at two sites located in the NE of the Iberian Peninsula, where recent mortality events have been recorded. Annual tree rings were used to (1) date dead trees; (2) investigate if there was an association between the occurrence of tree death and severe drought periods characterized by exceptionally low ratios of summer precipitation to potential evapotranspiration (P/PET); and (3) to compare the growth patterns of trees that died with those of surviving ones. Mixed models were used to describe the relationships between tree growth (in terms of basal area increment, BAI, and the percentage of latewood, LW%) and climate variables. Our results showed a direct association between Scots pine mortality and severe drought periods characterized by low summer water availability. At the two sites, the growth patterns of dead trees were clearly distinguishable from those of the trees that survived. In particular, the BAI of dead trees was more sensitive to climate dryness (low P/PET_summer, high temperatures) and started to decline below the values of surviving neighbors 15–40 years before the time of death, implying a slow process of growth decline preceding mortality.