Uusien lääkkeiden markkinoille tulo ja lääkekustannuksiin vaikuttaminen

Lääkekustannukset kasvoivat 2000-luvulla useimmissa teollistuneissa maissa terveydenhuollon kokonaismenoja nopeammin. Lääkkeiden rahoituksesta vastaavat ovatkin etsineet keinoja kustannusten kasvun hillitsemiseksi. Uudet, vanhoja lääkkeitä kalliimmat lääkkeet ovat yksi syy kustannusten kasvuun. Tämän tutkimuksen tarkoitus oli selvittää uusien, avohoidossa käytettävien lääkkeiden käyttöönottoa, hintoja ja kustannuksia sekä analysoida lääkkeen erityiskorvattavuutta edeltävän peruskorvattavuusjakson ja korvauksen rajoittamisen vaikutuksia lääkkeiden kulutukseen ja hoitojen kohdentumiseen. Tutkimusten aineistoina käytettiin muun muassa Lääkelaitoksen ja Kelan tietokantoja ja lääkkeiden tukkumyyntitietoja. Lääkkeiden hintatiedot Euroopan maista kerättiin kyselyllä. Suomen markkinoille tuli vuosina 1996–2005 lähes 300 uutta lääkeainetta. Vuonna 2005 niiden osuus avohoidon lääkemyynnin arvosta oli 38 % ja kulutuksesta 19 %. Avohoidossa uutuuksia tuli erityisesti syöpien, infektioiden ja sydän- ja verisuonisairauksien hoitoon. Osa uutuuksista tarjosi merkittäviä uusia hoitomahdollisuuksia, osan lisähyöty oli vähäinen. Tiukan hintasääntelyn maissa uusien lääkkeiden tukkuhinnat olivat alhaisemmat kuin niissä maissa, joissa ei ollut suoraa sääntelyä. Maan asema tukkuhintojen vertailussa ei kuitenkaan määrittänyt sen asemaa vähittäismyyntihintaisessa vertailussa, sillä apteekkien kate ja verot vaihtelevat maittain. Suomessa uusien lääkkeiden tukkuhinnat olivat eurooppalaista keskitasoa, mutta verolliset vähittäismyyntihinnat keskitasoa korkeammat. Glaukooma-lääkkeillä erityiskorvattavuutta edeltävä peruskorvattavuusjakso hidasti uusien valmisteiden käyttöönottoa. Lääkkeiden tultua erityiskorvattaviksi niiden käyttäjämäärä ja kulutus kasvoivat. Kalleimpien statiinien korvauksen rajoittaminen niille potilaille, joille edullisemmat eivät sovi, lisäsi edullisten statiinien käyttöä. Rajoituksen jälkeen kalleimmat statiinit kanavoituivat sairaammille ja aiemmin muita statiineja käyttäneille. Toimenpiteiden pitkäaikaisvaikutuksista ja terveysvaikutuksista ei ole tietoa.

The variants of the protein toxins abrin and ricin A useful guide to understanding the processing events in the toxin transport

Kinetic data on inhibition of protein synthesis in thymocyte by three abrins and ricin have been obtained. The intrinsic efficiencies of A chains of four toxins to inactivate ribosomes, as analyzed by k1-versus-concentration plots were abrin II, III > ricin > abrin I. The lag times were 90, 66, 75 and 105 min at a 0.0744 nM concentration of each of abrin I, II, III and ricin, respectively. To account for the observed differences in the dose-dependent lag time, functional and structural variables of toxins such as binding efficiency of B chains to receptors and low-pH-induced structural alterations have been analyzed. The association constants obtained by stopped flow studies showed that abrin-I (4.13 × 105 M−1 s−1) association with putative receptor (4-methylumbelliferyl-α-D-galactoside) is nearly two times more often than abrin III (2.6 × 105 M−1 s−1) at 20°C. Equillibrium binding constants of abrin I and II to thymocyte at 37°C were 2.26 × 107 M−1 and 2.8 × 107 M−1 respectively. pH-induced structural alterations as studied by a parallel enhancement in 8-anilino-L-naphthalene sulfonate fluorescence revealed a high degree of qualitative similarity. These results taken with a nearly identical concentration-independent lag time (minimum lag of 41–42 min) indicated that the binding efficiencies and internalization efficiencies of these toxins are the same and that the observed difference in the dose-dependent lag time is causally related to the proposed processing event. The rates of reduction of inter-subunit disulfide bond, an obligatory step in the intoxication process, have been measured and compared under a variety of conditions. Intersubunit disulfide reduction of abrin I is fourfold faster than that of abrin II at pH 7.2. The rate of disulfide reduction in abrin I could be decreased 1 I-fold by adding lactose, compared to that without lactose. The observed differences in the efficiencies of A chains, the dose-dependent lag period, the modulating effect of lactose on the rates of disulfide reduction and similarity in binding properties make the variants a valuable tool to probe the processing events in toxin transport in detail.

Application of a modified z-cosy experiment for the analysis of spectra of oriented molecules - the spectrum of cis,cis-mucanonitrile

NMR spectra of cis,cis-mucanonitrile oriented in a liquid crystal have been analysed using the connectivity information obtained from a modified Z-COSY experiment which provided crucial clues for the starting parameters for the iterative analysis. The proton spectra with and without C-13 satellites and the C-13 spectra have thus been interpreted. The indirect spin-spin couplings required for the analyses have been obtained from the corresponding isotropic spectra. The H-1-H-1 and C-13-H-1 dipolar couplings so obtained have been utilized to determine the relative internuclear distances. The results indicate that the molecule is planar. (C) 1994 Academic Press, Inc.

Characterization and Acceptor Preference of a Soluble Meningococcal Group C Polysialyltransferase

Vaccines against Neisseria meningitidis group C are based on its alpha-2,9-linked polysialic acid capsular polysaccharide. This polysialic acid expressed on the surface of N. meningitidis and in the absence of specific antibody serves to evade host defense mechanisms. The polysialyltransferase (PST) that forms the group C polysialic acid (NmC PST) is located in the cytoplasmic membrane. Until recently, detailed characterization of bacterial polysialyltransferases has been hampered by a lack of availability of soluble enzyme preparations. We have constructed chimeras of the group C polysialyltransferase that catalyzes the formation alpha-2,9-polysialic acid as a soluble enzyme. We used site-directed mutagenesis to determine the region of the enzyme necessary for synthesis of the alpha-2,9 linkage. A chimera of NmB and NmC PSTs containing only amino acids 1 to 107 of the NmB polysialyltransferase catalyzed the synthesis of alpha-2,8-polysialic acid. The NmC polysialyltransferase requires an exogenous acceptor for catalytic activity. While it requires a minimum of a disialylated oligosaccharide to catalyze transfer, it can form high-molecular-weight alpha-2,9-polysialic acid in a nonprocessive fashion when initiated with an alpha-2,8-polysialic acid acceptor. De novo synthesis in vivo requires an endogenous acceptor. We attempted to reconstitute de novo activity of the soluble group C polysialyltransferase with membrane components. We found that an acapsular mutant with a defect in the polysialyltransferase produces outer membrane vesicles containing an acceptor for the alpha-2,9-polysialyltransferase. This acceptor is an amphipathic molecule and can be elongated to produce polysialic acid that is reactive with group C-specific antibody.

Nonlinear effects on rotating disk flow in a cylindrical casing

The flow due to a finite disk rotating in an incompressible viscous fluid has been studied. A modified Newton-gradient finite difference scheme is used to obtain the solution of full Navier-Stokes equations numerically for different disk and cylinder sizes for a wide range of Reynolds numbers. The introduction of the aspect ratio and the disk-shroud gap, significantly alters the flow characteristics in the region under consideration, The frictional torque calculated from the flow data reveals that the contribution due to nonlinear terms is not negligible even at a low Reynolds number. For large Reynolds numbers, the flow structure reveals a strong boundary layer character.

Phase Separation in Binary Nearly-Hard-Sphere Colloids: Evidence for the Depletion Force

A binary aqueous suspension of large (L) and small (S) nearly-hard-sphere colloidal polystyrene spheres is shown to segregate spontaneously into L-rich and S-rich regions for suitable choices of volume fraction and size ratio. This is the first observation of such purely entropic phase separation of chemically identical species in which at least one component remains fluid. Simple theoretical arguments are presented to make this effect plausible.

Nanoparticles of SrTiO3 prepared by gel to crystallite conversion and their photocatalytic activity in the mineralization of phenol

Nanometre-sized powders of SrTiO3 were prepared at 70-100 degrees C by the wet-chemical method of gel to crystallite (G-C) conversion. The crystallite sizes obtained were in the range 5-13 nm, as estimated by transmission electron microscopy (TEM) studies. The photocatalytic activities of these powders in the mineralization of phenol were evaluated in comparison with Degussa P25 (TiO2). The maximum photocatalytic activity was observed for powders annealed in the range 1100-1300 degrees C. The optical spectra of the particle suspensions in water showed broadened absorption around the band gap region, together with the appearance of an absorption maximum in the UV region. The effect of inorganic oxidizing species as electron scavengers on the rate of the photocatalytic degradation of phenol was studied. The influence of bulk and surface defects, which participate in the charge transfer process during photocatalysis, was investigated systematically.