Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro

BACKGROUND: Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company. METHODS: The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism. RESULTS: The drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K(1)) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilisers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilisers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity. CONCLUSION: This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen no longer detectable in pharmaceutical-grade albumin. It further shows that the addition of stabilisers may be of major importance for this effect

Spatial Clustering of Porcine Cysticercosis in Mbulu District, Northern Tanzania

Taenia solium is a tapeworm that causes two different disease conditions. In its adult stage, it inhabits the small intestine of human, a condition known as taeniosis, which is characterised by mild symptoms including abdominal disconfort. In the larval stage, T. solium can infect humans and various animal species, mainly pigs, causing cysticercosis. Taeniosis is acquired through consumption of inadequately cooked infected meat, while cysticercosis is acquired through ingestion of tapeworm eggs in foodstuffs contaminated with faeces from a human tapeworm carrier. Cysticercosis of human central nervous tissues (neurocysticercosis) causes serious syndromes such as epilepsy. Transmission of T. solium is facilitated by several factors such as presence of tapeworm carriers, poor sanitation and poor pig husbandry, which allow pigs to access human faeces. Nevertheless, the role of these factors in parasite transmission may vary with different cultural settings. Following an incidence and a prevalence studies in a rural area of northern Tanzania, there was a significant spatial clustering of porcine cysticerocis, suggesting focal distribution of transmission risk factors, which could be targeted for interventions. The study also revealed that despite the low sensitivity of the lingual examination method to detect porcine cysticercosis, it could highlight the potential ‘hotspots’ of the infection

Self-consistent quantal treatment of decay rates within the perturbed static path approximation

The framework of the Perturbed Static Path Approximation (PSPA) is used to calculate the partition function of a finite Fermi system from a Hamiltonian with a separable two body interaction. Therein, the collective degree of freedom is introduced in self-consistent fashion through a Hubbard-Stratonovich transformation. In this way all transport coefficients which dominate the decay of a meta-stable system are defined and calculated microscopically. Otherwise the same formalism is applied as in the Caldeira-Leggett model to deduce the decay rate from the free energy above the so called crossover temperature $T_0$.Comment: 17 pages, LaTex, no figures; final version, accepted for publication in PRE; e-mail: [email protected]

Coherent pion production in neutrino nucleus collision in the 1 GeV region

We calculate cross sections for coherent pion production in nuclei induced by neutrinos and antineutrinos of the electron and muon type. The analogies and differences between this process and the related ones of coherent pion production induced by photons, or the (p,n) and $(^3 He, t)$ reactions are discussed. The process is one of the several ones occurring for intermediate energy neutrinos, to be considered when detecting atmospheric neutrinos. For this purpose the results shown here can be easily extrapolated to other energies and other nuclei.Comment: 13 pages, LaTex, 8 post-script figures available at [email protected]

Contributions to the revision of the genus Entoloma (Basidiomycota, Agaricales) in Europe : six new species from subgenus Cyanula and typification of E. incarnatofuscescens

In anticipation of a phylogenetically revised monograph of Entoloma in Europe, six new species of subgenus Cyanula are described here. Entoloma cistocruentatum is associated with Cistus in Spain, E. dislocatum occurs in montane regions in Catalonia (Spain) and Tuscany (Italy), E. indikon is known from Denmark and three species are mainly distributed in the Nordic countries in Europe: E. calceus , E. perchalybeum and E. praecipuum. Entoloma incarnatofuscescens, from the /Rusticoides clade is neotypified. A fully amended description is given based on molecular evidence, which includes the recently described E. violaceoparkensis and E. klofacianum which became later synonyms.publishedVersio

Secular changes in dementia risk indices among 70-year-olds: a comparison of two Finnish cohorts born 20 years apart

AimsTo compare dementia risk indices among two separate cohorts of 70-year-olds born 20 year apart.MethodsCommunity-dwelling 70-year-old Finns were examined with similar examinations in 1991 (n = 1032) and in 2011 (n = 960). Dementia risk was assessed with the CAIDE Dementia Risk Score (CAIDE) (n = 1516), the Brief Dementia Risk Index (BDRI) (n = 1598) and the Dementia Screening Indicator (DSI) (n = 1462).ResultsThe proportion of subjects with moderate or high risk for dementia was significantly higher in earlier than in later born cohort according to CAIDE (99% and 94%, respectively, p ConclusionsAccording to dementia risk indices, it seems that dementia risk has decreased among community-dwelling 70-year-old subjects during the last decades in Finland.</p

Delta excitation in K^+-nucleus collisions

We present calculations for \Delta excitation in the (K^+,K^+) reaction in nuclei. The background from quasielastic K^+ scattering in the \Delta region is also evaluated and shown to be quite small in some kinematical regions, so as to allow for a clean identification of the \Delta excitation strength. Nuclear effects tied to the \Delta renormalization in the nucleus are considered and the reaction is shown to provide new elements to enrich our knowledge of the \Delta properties in a nuclear medium.Comment: 11 pages, 6 figures, LaTe

Overprinted allocyclic processes by tidal resonance in an epicontinental basin: the Upper Jurassic Curtis Formation, east‐central Utah, USA

Modern, tide‐dominated and tide‐influenced coastlines are characterised by a range of environments, including deltas, estuaries, and lagoons. However, some tide‐dominated basins and related sedimentary units in the rock record, such as the semi‐enclosed, shallow, Utah‐Idaho Trough foreland basin of the Jurassic Curtis sea, do not correspond to any of these modern systems. Persistent aridity caused the characteristic severe starvation of perennial fluvial input throughout this basin, in which the informal lower, middle, and upper Curtis, as well as the underlying Entrada Sandstone, and the overlying Summerville Formation were deposited. Wave energy was efficiently dissipated by the shallow basin's elongated morphology (approximately 800x150 km), as its semi‐enclosed morphology further protected the system from significant wave impact. Consequently, the semi‐enclosed, shallow‐marine system was dominated by amplified tidal forces, resulting in a complex distribution of heterolithic deposits. Allocyclic forcing strongly impacted upon the system's intrinsic autocyclic processes as the lower Curtis was deposited. Short‐lived relative sea‐level variations, along with uplift and deformation episodes, resulted in the accumulation of three parasequences, each separated by traceable flooding and ravinement surfaces. The subsequent transgression, which defines the base of the middle Curtis, allowed for the shallow‐marine part of the system to enter into tidal resonance as a consequence of the flooded basin reaching the optimal configuration of approximately 800 km in length, corresponding to an odd multiple of the quarter of the tidal wavelength given an average minimum water depth of 20 to 25 m. This resonant system overprinted the effects of allocyclic forcing and related traceable stratigraphic surfaces. However, the contemporaneous and neighbouring coastal dune field sedimentary rocks of the Moab Member of the Curtis Formation, characterised by five stacked aeolian sequences, as well as the supratidal deposits of the Summerville Formation, lingered to record allocyclic signals, as the Curtis sea regressed. This study shows that a tide‐dominated basin can enter into tidal resonance as it reaches its optimal morphological configuration, leading to the overprinting of otherwise dominant allocyclic processes by autocyclic behaviour. It is only by considering the sedimentological relationships of neighbouring and contemporaneous depositional systems that a full understanding of the dynamic stratigraphic history of a basin alternatively dominated by autocyclic and allocyclic processes can be achieved

A holistic and comprensive data approach validates the distribution of the critically endangered flapper skate (Dipturus intermedius)

Morphological similarities between skates of the genus Dipturus in the north-eastern Atlantic and mediterranean have resulted in longstanding confusion, misidentification and misreporting. Current evidence indicates that the common skate is best explained as two species, the flapper skate (Dipturus intermedius) and the common blue skate (D. batis). However, some management and conservation initiatives developed prior to the separation continue to refer to common skate (as ‘D. batis’). This taxonomic uncertainty can lead to errors in estimating population viability, distribution range, and impact on fisheries management and conservation status. Here, we demonstrate how a concerted taxonomic approach, using molecular data and a combination of survey, angler and fisheries data, in addition to expert witness statements, can be used to build a higher resolution picture of the current distribution of D. intermedius. Collated data indicate that flapper skate has a more constrained distribution compared to the perceived distribution of the ‘common skate’, with most observations recorded from Norway and the western and northern seaboards of Ireland and Scotland, with occasional specimens from Portugal and the Azores. Overall, the revised spatial distribution of D. intermedius has significantly reduced the extant range of the species, indicating a possibly fragmented distribution range.acceptedVersio