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T Heikkilä

Publications and source records attributed to T Heikkilä.

8 recordsLinked to original sources
PubMed2006

Mesoporous silica material TUD-1 as a drug delivery system.

For the first time the feasibility of siliceous mesoporous material TUD-1 (Technische Universiteit Delft) for drug delivery was studied. Model drug, ibuprofen, was adsorbed into TUD-1 mesopores via a soaking procedure. Characterizations with nitrogen adsorption, XRD, TG, HPLC and DSC demonstrated the successful inclusion of ibuprofen into TUD-1 host. The amount of ibuprofen adsorbed into the nanoreservoir of TUD-1 material was higher than reported for other mesoporous silica drug carriers (drug/carrier 49.5 wt.%). Drug release studies in vitro (HBSS buffer pH 5.5) demonstrated a fast and unrestricted liberation of ibuprofen, with 96% released at 210 min of the dissolution assay. The drug dissolution profile of TUD-1 material with the random, foam-like three-dimensional mesopore network and high accessibility to the dissolution medium was found to be much faster (kinetic constant k = 10.7) and more diffusion based (release constant n = 0.64) compared to a mesoporous MCM-41 material with smaller, unidirectional mesopore channels (k = 4.7, n = 0.71). Also, the mesoporous carriers were found to significantly increase the dissolution rate of ibuprofen, when compared to the pure crystalline form of the drug (k = 0.6, n = 0.96). TUD-1 was constituted as a potential drug delivery device with fast release property, with prospective applications in the formulation of poorly soluble drug compounds.

Adsorption↗
PubMed2006

Synthesis of Pt modified ZSM-5 and beta zeolite catalysts: influence of ultrasonic irradiation and preparation methods on physico-chemical and catalytic properties in pentane isomerization.

Influence of preparation methods and ultrasound irradiation on physico-chemical and catalytic properties was investigated by synthesizing Pt-ZSM-5 and Pt-Beta catalysts by in-situ and impregnation methods and applying ultrasound irradiation to synthesis gel mixture of ZSM-5 and Beta zeolites. It was concluded from the X-ray powder diffraction patterns of Pt-ZSM-5 and Pt-Beta zeolite catalysts that introduction of Pt by in-situ method and ultrasound irradiation did not influence the structures of ZSM-5 and Beta zeolites. Morphology of ZSM-5 and Beta zeolites were investigated by scanning electron microscopy. SEM micrographs showed that the Pt-ZSM-5-IS-US catalyst synthesized by in-situ method with ultrasound irradiation resulted in smaller crystals of ZSM-5 than Pt-ZSM-5-IS catalyst prepared without ultrasound irradiation. Furthermore SEM micrographs of Pt-Beta-11-IS-US zeolite synthesized using ultrasound irradiation showed much smaller crystals than Pt-Beta-11-IM indicating that ultrasound irradiation had a significant effect on the morphology of Beta zeolite. Conversion of n-pentane and selectivity to iso-pentane over the Pt-ZSM-5-IS-US zeolite catalysts prepared by ultrasound irradiation during in-situ introduction of platinum was higher than the catalysts prepared without the ultrasound irradiation. Furthermore ultrasound irradiated and in-situ synthesized Pt-Beta-11-IS-US catalyst also showed higher selectivity to iso-pentane than Pt-H-Beta-11-IM prepared by impregnation method.

Journal Article↗
PubMed2005

Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs.

Mesoporous silicon (PSi) microparticles were produced using thermal carbonization (TCPSi) or thermal oxidation (TOPSi) to obtain surfaces suitable for oral drug administration applications. The loading of five model drugs (antipyrine, ibuprofen, griseofulvin, ranitidine and furosemide) into the microparticles and their subsequent release behaviour were studied. Loading of drugs into TCPSi and TOPSi microparticles showed, that in addition to effects regarding the stability of the particles in the presence of aqueous or organic solvents, surface properties will affect compound affinity towards the particle. In addition to the surface properties, the chemical nature of the drug and the loading solution seems to be critical to the loading process. This was reflected in the obtained loading efficiencies, which varied between 9% and 45% with TCPSi particles. The release rate of a loaded drug from TCPSi microparticles was found to depend on the characteristic dissolution behaviour of the drug substance. When the dissolution rate of the free/unloaded drug was high, the microparticles caused a delayed release. However, with poorly dissolving drugs, the loading into the mesoporous microparticles clearly improved dissolution. In addition, pH dependency of the dissolution was reduced when the drug substance was loaded into the microparticles.

Administration, Oral↗
PubMed2001

Complement evasion by Borrelia burgdorferi: serum-resistant strains promote C3b inactivation.

The most characteristic features of the Lyme disease pathogens, the Borrelia burgdorferi sensu lato (s.l.) group, are their ability to invade tissues and to circumvent the immune defenses of the host for extended periods of time, despite elevated levels of borrelia-specific antibodies in serum and other body fluids. Our aim in the present study was to determine whether B. burgdorferi is able to interfere with complement (C) at the level of C3 by accelerating C3b inactivation and thus to inhibit the amplification of the C cascade. Strains belonging to different genospecies (Borrelia garinii, B. burgdorferi sensu stricto, and Borrelia afzelii) were compared for their sensitivities to normal human serum and abilities to promote factor I-mediated C3b degradation. B. burgdorferi sensu stricto and B. afzelii strains were found to be serum resistant. When the spirochetes were incubated with radiolabeled C3b, factor I-mediated degradation of C3b was observed in the presence of C-resistant B. afzelii (n = 3) and B. burgdorferi sensu stricto (n = 1) strains but not in the presence of C-sensitive B. garinii (n = 7) strains or control bacteria (Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis). Immunoblotting and radioligand binding analyses showed that the C-resistant strains had the capacity to acquire the C inhibitors factor H and factor H-like protein 1 (FHL-1) from growth medium and human serum. A novel surface protein with an apparent molecular mass of 35 kDa was found to preferentially bind to the N terminus region of factor H. Thus, the serum-resistant B. burgdorferi s.l. strains can circumvent C attack by binding the C inhibitors factor H and FHL-1 to their surfaces and promoting factor I-mediated C3b degradation.

Animals↗
PubMed2001

Recombinant flagellin A proteins from Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii in serodiagnosis of Lyme borreliosis.

Genes for flagellin A (FlaA) proteins from European borrelial strains of Borrelia burgdorferi sensu stricto, B. afzelii, and B. garinii were cloned and sequenced. An identity of 92 to 93% was observed in the flaA sequences of the different species. Polyhistidine-tagged recombinant FlaA (rFlaA) proteins were produced in Escherichia coli and used as antigens in Western blotting (WB) and enzyme-linked immunosorbent assay (ELISA). In immunoglobulin G (IgG) WB, 71% (10 of 14) of the sera from neuroborreliosis and 86% (12 of 14) of those from Lyme arthritis patients reacted with one to three rFlaAs. In IgG ELISA, 74% (14 of 19) and 79% (15 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. The immunoreactivity in local European patient sera was stronger against rFlaA from B. garinii and B. afzelii than against rFlaA from B. burgdorferi sensu stricto. Neither IgG nor IgM ELISA was sensitive in the serodiagnosis of erythema migrans. Serum samples from patients with syphilis and systemic lupus erythematosus showed mild cross-reactivity in IgG tests. Sera from Yersinia enterocolitica or beta-hemolytic Streptococcus infections showed only occasional responses. With IgM ELISA, 58% (11 of 19) and 37% (7 of 19) of patients with neuroborreliosis and arthritis, respectively, were positive. Cross-reactive antibodies to FlaA, especially in serum samples from patients with rheumatoid factor positivity and Epstein-Barr virus infection, reduced the specificity of IgM serodiagnosis. Therefore, rFlaA seems to have a limited role for IgM serodiagnosis, yet rFlaA might be useful in the IgG serodiagnosis of disseminated Lyme borreliosis.

Amino Acid Sequence↗
PubMed2000

The complement regulator factor H binds to the surface protein OspE of Borrelia burgdorferi.

Spirochete bacteria of the Borrelia burgdorferi sensu lato complex cause Lyme borreliosis. The three pathogenic subspecies Borrelia garinii, Borrelia afzelii, and Borrelia burgdorferi sensu stricto differ in their disease profiles and susceptibility to complement lysis. We investigated whether complement resistance of Borreliae could be due to acquisition of the main soluble inhibitors of the alternative complement pathway, factor H and the factor H-like protein 1. When exposed to nonimmune EDTA-plasma, the serum-resistant B. afzelii and B. burgdorferi sensu stricto strains bound factor H/factor H-like protein 1 to their surfaces. Assays with radiolabeled proteins showed that factor H bound strongly to the B. burgdorferi sensu stricto strain. To identify factor H ligands on the borrelial surface, we analyzed a panel of outer surface proteins of B. burgdorferi sensu stricto with the surface plasmon resonance technique. The outer surface lipoprotein OspE was identified as a specific ligand for factor H. Using recombinant constructs of factor H, the binding site for OspE was localized to the C-terminal short consensus repeat domains 15-20. Specific binding of factor H to B. burgdorferi sensu stricto OspE may help the pathogen to evade complement attack and phagocytosis.

Antigens, Bacterial↗
PubMed1996

Predictors of outcome of short-term child psychiatric inpatient treatment.

In this study, 85 children were prospectively followed after discharge from short-term inpatient treatment. Outcome was defined as functioning within normal range at the follow-up or as improvement in the child's behavior problems. Rutter Parent's Questionnaire was used as a measure on admission and at the 5-month follow-up after discharge. The child's more frequent individual behavior problems, antisocial behavior and disengaged family interaction on admission predicted both functioning outside normal range and less improvement at follow-up. Previous treatment because of developmental or behavioral problems and hyperkinetic symptoms on admission predicted functioning outside normal range. Parent's previous psychiatric hospital treatment was negatively associated with improvement. Pure emotional disorder predicted normal range functioning at follow-up. The child's age, gender, place of treatment and length of short-term treatment were not related to outcome. The results also stress the importance of taking into account both parents' and teachers' evaluations on admission.

Adolescent↗